Myelodysplastic SyndromePhase 1/2NCT00520130

Chemotherapy and Unrelated Donor Stem Cell Transplantation for Patients With Cancers of the Blood and Immune System

A Phase 1/2 study testing Rituximab, Cyclosporine and Allogenic stem cell transplant (ASCT) in people with Myelodysplastic Syndrome and Hodgkin's Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Background: Major problems with stem cell transplantation (SCT) for cancer treatment are a lack of suitable donors for patients without a human leukocyte-antigen (HLA) tissue-matched sibling and graft-versus-host disease (GVHD), a serious side effects of immune-suppressing chemotherapy that is given to bring the… Read more about this study

Who is it for?: Ages 18 to 74 years
Conditions the study is for: Myelodysplastic Syndrome, Hodgkin's Lymphoma, Non-Hodgkin's Disease
What is being tested?: Rituximab, Cyclosporine and Allogenic stem cell transplant (ASCT)
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 92 participants
Where: 1 siteUnited States
Study dates: 30 Oct 2007to 31 Dec 2018
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 74 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

None listed.

Who cannot join

Human immunodeficiency virus (HIV) infection. There is theoretical concern that the degree of immune suppression associated with the treatment may result in progression of HIV infection.
Pregnant or lactating. Patients of childbearing potential must use an effective method of contraception. The effects of the chemotherapy, the subsequent transplant and the medications used after the transplant are highly likely to be harmful to a fetus. The effects upon breast milk are also unknown and may be harmful to the infant.

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Phase II Trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation Using 8/8 and 7/8 HLA-matched Unrelated Donors and Utilizing Two Graft-versus-Host Disease Prophylaxis Regimens for the Treatment of Leukemias, Lymphomas, and Pre-malignant Blood Disorders

Background:

Major problems with stem cell transplantation (SCT) for cancer treatment are a lack of suitable donors for patients without a human leukocyte-antigen (HLA) tissue-matched sibling and graft-versus-host disease (GVHD), a serious side effects of immune-suppressing chemotherapy that is given to bring the cancer under control before SCT. In GVHD, the patients immune system attacks the transplanted donor cells.

This study will try to improve the results of SCT from unrelated HLA-matched donors using targeted immune-depleting chemotherapy to bring the cancer under control before transplantation and to lower the chance of graft rejection, followed by reduced-intensity transplant chemotherapy to make the procedure less toxic.

Objectives:

To evaluate the safety and effectiveness of targeted immune-depleting chemotherapy followed by reduced-intensity transplant chemotherapy in patients with advanced cancers of the blood and immune system.

To evaluate the safety and effectiveness of two different drug combinations to prevent GVHD. Both regimens have been successful in preventing GVHD, but they work by different mechanisms and affect the rebuilding of the immune system after the transplant.

Eligibility:

People 18 to 74 years of age with advanced or high-risk cancers of the blood and immune system who do not have a suitable HLA-matched sibling.

Design:

All patients receive chemotherapy before transplant to treat the cancer and suppress immune function.

All patients receive a conditioning regimen of cyclophosphamide for 4 days and fludarabine for 4 days before SCT to prepare for the transplant.

Patients are randomly assigned to one of two combination drug treatments to prevent GHVD as follows:

Group 1: Tacrolimus starting 3 days before SCT and continuing for 6 months, plus methotrexate on days 1, 3, 6, and 11 post-SCT, plus sirolimus starting 3 days before the SCT and continues for 6 months following SCT.
Group 2: Alemtuzumab for 4 days starting 8 days before SCT, plus cyclosporine starting 1 day before SCT and continuing for 6 months.

Patients receive the donors stem cells and immune cells 2 days after completing the conditioning regimen.

Patients are followed at the clinic regularly for the first 6 months after SCT, and then less often for at least 5 years. Some visits may include bone marrow aspirates and biopsies, blood draws, and other tests to monitor disease status.

A skin biopsy, oral mucosa biopsy, and saliva collection are done to study chronic GVHD.

...

Read the detailed description

Background:

The major limitations to the broader applicability of allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of malignancies are lack of suitable donors and therapy-related toxicities which include delayed and incomplete immune reconstitution and graft-versus-host disease (GVHD). Based on the theory that the rapid establishment of donor chimerism was essential for an optimal graft-versus-tumor effect, we have employed a strategy of targeted immune depleting chemotherapy prior to reduced-intensity allogeneic HSCT. It is our intent to investigate this approach in the setting of human leukocyte-antigen (HLA)-matched unrelated donors in a pilot manner.
A clearly superior GVHD prophylaxis regimen has not been established in the unrelated donor transplant setting. The best results that have been reported are with the combination of alemtuzumab plus cyclosporine [AC] and the combination of tacrolimus, methotrexate, and sirolimus [TMS]. These two regimens work by mechanisms which are biologically distinct and potentially have markedly different effects upon immune reconstitution that have not been well studied. In addition, neither of these regimens has been assessed for their effects on chronic GVHD using the National Institutes of Health (NIH) Consensus Conference Criteria. It is our intent to study the effects that these two regimens have on immune reconstitution and chronic GVHD in the setting sequential targeted immune-depleting chemotherapy and reduced-intensity allogeneic HSCT from HLA-matched unrelated donors.

Objectives:

Primary objectives:

to assess the effects of two biologically distinct GVHD prophylaxis regimens, TMS and AC, on immune reconstitution in patients receiving targeted-immune depletion and reduced-intensity allogeneic HSCT from HLA-matched unrelated donors. As part of a comprehensive assessment of immune reconstitution, the primary immunologic endpoint will be the determination of cluster of differentiation 4 (CD4)+ T cell receptor V BETA repertoire by complementarity determining region 3 (CDR3) spectratyping at 3 months post-transplant.
to assess overall safety of these two regimens in this setting, as determined by engraftment, acute GVHD, early and late treatment-related mortality, and overall survival.
to determine and monitor incidence, organ severity and overall severity of chronic GVHD prospectively using the newly developed NIH Consensus Conference diagnosis and staging criteria and preliminarily validate those tools for use in clinical practice and trials.

Secondary objectives include further assessment of immune reconstitution, study of engraftment kinetics, and assessment of those patients who receive higher doses of anthracyclines for long and short term toxicities

Eligibility:

Adults (18-74 years) with advanced or high risk hematologic malignancies including acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL), non-hodgkin lymphoma (NHL), hodgkin lymphoma (HL), chronic myelogenous leukemia (CML), multiple myeloma, and myeloproliferative disorder (MPD) who lack a suitable HLA matched sibling.
An unrelated donor matched at a minimum of 7 of 8 alleles (HLA-A,-B,-C, and DRB1) by high resolution typing, identified through the National Marrow Donor Program.
Life expectancy of at least 3 months, Eastern Cooperative Oncology Group (ECOG) less than or equal to 2 and relatively normal major organ functions.

Design:

Patients will receive disease-specific induction chemotherapy (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH-fludarabine (F)/rituximab (R) or fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG)) prior to transplant for disease control and immune depletion. If disease is controlled (greater than partial response (PR)) and immune depletion objectives have been met, patients may forgo induction chemotherapy and move forward to the transplant conditioning regimen.
All patients will receive an identical conditioning regimen consisting of cyclophosphamide 1200 mg/m(2)/day intravenous (IV) for 4 days and fludarabine 30 mg/m(2)/day for 4 days.
Patients will be stratified according to degree of HLA-match and randomized at the time of enrollment to one of two GHVD prophylaxis regimens:
Group 1: Tacrolimus starting 3 days before stem cell transplant (SCT), and continuing for 6 months, plus methotrexate on days 1, 3, 6, and 11 post-SCT, plus sirolimus starting 3 days before the SCT and continues for 6 months following SCT.
Group 2: Alemtuzumab for 4 days starting 8 days before SCT, plus cyclosporine starting 1 day before SCT and continuing for 6 months.
A maximum of 105 patients will be enrolled and randomly assigned to the two arms in order to yield 44 patients per arm (88 total patients) who are able to be evaluated for development of severe chronic GVHD.

Conditions: Myelodysplastic Syndrome, Hodgkin's Lymphoma, Non-Hodgkin's Disease, Acute Leukemia, Multiple Myeloma
Being tested: Rituximab, Cyclosporine, Allogenic stem cell transplant (ASCT), Conditioning Chemotherapy, TMS
Keywords: Unrelated Donors, Reduced Intensity Stem Cell Transplant, Leukemia, Lymphoma, Allogeneic Stem Cell Transplant, Myelodysplastic Syndrome, Multiple Myeloma
Medical subject headings: Myelodysplastic Syndromes, Hodgkin Disease, Multiple Myeloma, Leukemia, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RituximabBiological
Also called Rituxan
Rituximab: 375 mg/m(2) intravenous (IV), day 1 for patients with cluster of differentiation 20 (CD20)-positive disease.
CyclosporineDrug
Also called Neoral
Cyclosporine: IV over 2 hours or orally every 12 hours on days -1 to 100, followed by a taper if graft versus host disease (GVHD) does not develop.
Allogenic stem cell transplant (ASCT)Drug
Allogenic stem cell transplant
Conditioning ChemotherapyDrug
Fludarabine:30 mg/m(2) per day IV infusion over 30 minutes, daily. On days -6, -5, -4, and -3.
Cyclophosphamide:1200 mg/m(2) per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna: 1200 mg/m(2) per day IV infusion, Daily on days 6, -5,-4, and -3
TMSDrug
Also called Prograf
Tacrolimus: starting day -3 before transplant, given initially at 0.02 mg/kg/day CIV. Continue IV and then switch to an equivalent oral dose (when patient taking po) titrated for a goal level of 5 to 10 ng/ml; Sirolimus: given as an initial loading dose of 12 mg p.o. on day -3 pre-transplant, 4 mg starting day -2 pre-transplant and titrated for levels 3-12 ng/ml; Methotrexate 5 mg/m2 IV on days +1, +3, +6, and +11 post-transplant. Tacrolimus and sirolimus will be tapered at day +63, day +119 and day +180 post-transplant as tolerated.
FLAGDrug
Also called Fludarabine+high-dose cytarabine+G-CSF (Filgrastim))
Fludarabine:25 mg/m(2) per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m(2) IV over 4 hours,on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day subcutaneous (SC) beginning 24 hours PRIOR to initiation of chemotherapy
EPOCH-FDrug
Fludarabine:25 mg/m(2) per day IV infusion over 30 minutes, daily on days 1-4 Etoposide :50 mg/m(2) per day continuous IV infusion over 24 hours on days 1-4 Doxorubicin:10 mg/m(2)/day CIV, days 1-4 Vincristine:0.4 mg/m(2) per day continuous IV infusion over 24 hours daily on days 1-4 Cyclophosphamide:750 mg/m(2) IV infusion over 30 minutes on day 5
AlemtuzumabBiological
Also called Campath
Alemtuzumab:20 mg/day IV over 8 h on days 8 to 4 pre-transplant.

Study groups in NCT00520130
Study group	Role	What they receive
A - Tacrolimus, methotrexate, sirolimus (TMS) Arm	Experimental	TMS Arm Receives: Biological: Rituximab; Drug: Allogenic stem cell transplant (ASCT); Drug: Conditioning Chemotherapy; Drug: TMS; Drug: FLAG; Drug: EPOCH-F
B - Cyclosporine (AC) Arm	Experimental	AC Arm Receives: Biological: Rituximab; Drug: Cyclosporine; Drug: Allogenic stem cell transplant (ASCT); Drug: Conditioning Chemotherapy; Drug: FLAG; Drug: EPOCH-F; Biological: Alemtuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants With Grade II-IV Acute Graft Versus Host Disease (GVHD)
Acute GVHD is assessed by the 1994 Consensus Conference on Acute GVHD Grading criteria. See Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995; 15:825-8., for grading criteria.
Measured: 6 months
Percentage of Participants With Chronic Graft Versus Host Disease (cGVHD)
Chronic GVHD is assessed by the 2005 Chronic GVHD Consensus Project. First the individual organ scoring is done, and then based on that the Global score is determined (mild-moderate-severe). See Citation: Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11:945-56., for grading criteria.
Measured: 2 years post transplant
Recovery of Naïve Cluster of Differentiation 4 (CD4) T Cells
The percentage of C-C motif chemokine receptor 7 (CCR7)+CD45RA+ naïve T cells within the CD4 T cell populations was determined by flow cytometry.
Measured: Recipient recovery at 6, 12 and 24 months post transplant
Recovery of Naïve Cluster of Differentiation 8 (CD8) T Cells
The percentage of CCR7+CD45RA+ naïve T cells within the CD4 and CD8 T cell populations was determined by flow cytometry.
Measured: Recipient recovery at 6, 12 and 24 months post transplant
Changes in Cluster of Differentiation 4 (CD4) T Cell Receptor Vbeta Repertoire
Ribonucleic acid (RNA) was extracted from sorted CD4 and cluster of differentiation 8 (CD8) T cells and analyzed for Vbeta repertoire by nested polymerase chain reaction (PCR) analysis using Vbeta family specific primers and a labeled constant region primer (spectratyping). The receptor repertoire diversity was calculated from spectratyping data by creating a normal standard for repertoire diversity from healthy normal controls and assessing the divergence of individual patient's T cell receptor repertoire from these standard normal donor values. In this Vbeta repertoire divergence index, lower numbers are consistent with a more normal highly diverse repertoire, and high numbers represent a highly skewed, oligoclonal repertoire. The assay is described in Memon SA et al, J Immunol Methods, 2012, 375: 84-92. The repertoire diversity of the CD4 and CD8 T cells of the donor infusion is shown for comparison.
Measured: Donor at time of collection and recipient at 1, 3, 6 and 12 months post transplant
Changes in CD8 T Cell Receptor Vbeta Repertoire
Ribonucleic acid (RNA) was extracted from sorted CD4 and cluster of differentiation 8 (CD8) T cells and analyzed for Vbeta repertoire by nested polymerase chain reaction (PCR) analysis using Vbeta family specific primers and a labeled constant region primer (spectratyping). The receptor repertoire diversity was calculated from spectratyping data by creating a normal standard for repertoire diversity from healthy normal controls and assessing the divergence of individual patient's T cell receptor repertoire from these standard normal donor values. In this Vbeta repertoire divergence index, lower numbers are consistent with a more normal highly diverse repertoire, and high numbers represent a highly skewed, oligoclonal repertoire. The assay is described in Memon SA et al, J Immunol Methods, 2012, 375: 84-92. The repertoire diversity of the CD4 and CD8 T cells of the donor infusion is shown for comparison.
Measured: Donor at time of collection and recipient at 1, 3, 6 and 12 months post transplant

Secondary outcomes (12)

Percentage of Participants With Grade III-IV Acute Graft Versus Host Disease (GVHD)
Acute GVHD is assessed by the 1994 Consensus Conference on acute GVHD Grading criteria. See Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995; 15:825-8., for grading criteria.
Measured: 6 months
Toxicities
Here are the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Measured: 103 months and 22 days
Days to Engraftment of Neutrophils
Days to engraftment is defined as neutrophil recovery: designated by the first of 3 consecutive days with an absolute neutrophil count (ANC) above 500/mm(3).
Measured: 2 years
Days to Engraftment of Platelets
Platelet recovery: designated by the first of 7 days where the platelet count remains above 20,000/mm(3) without transfusion support
Measured: 2 years
Days to Engraftment of Lymphocytes
Lymphocyte recovery: designated by the first of 3 consecutive days with absolute lymphocyte count (ALC) above 500/mm(3).
Measured: 2 years
Overall Survival
Time between the first day of transplant to the day of death.
Measured: Patients were followed for an average of up to 5 years.
Early Treatment Related Mortality
Any death occurring within 28 days after transplantation in a patient in continuous remission.
Measured: Less than or equal to 28 days after transplantation
Percentage of Participants With Late Treatment Related Mortality
Any death occurring 28 days or more after transplantation in a patient in continuous remission.
Measured: Greater than 28 days after transplantation
Decline in Homeostatic Cytokine Interleukin 7 (IL-7) Post-Transplant
During depletion of lymphocytes during transplant conditioning, levels of homeostatic cytokines increase in the blood. These then decline with the expansion of new donor-derived cells. The rapidity of decline may predict acute graft versus host disease (AGVHD). Decline in cytokine IL-7 will be assessed by the enzyme-linked immunosorbent assay (ELISA).
Measured: Day 0, 1 week and 2 weeks
Immune Reconstitution of Normal Killer (NK) Cells
Cluster of differentiation 3 (CD3) - cluster of differentiation 56 (CD56) + Natural Killer (NK) cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count.
Measured: 2 weeks, and 1, 3, 6, 12, and 24 months post transplant
Immune Reconstitution of Cluster of Differentiation 4 (CD4) T Cell Populations
Cluster of Differentiation 3 (CD3)+CD4+ and CD3+Cluster of Differentiation 8 (CD8)+ T cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count.
Measured: 2 weeks, and 1, 3, 6, 12 and 24 months post transplant
Immune Reconstitution of Cluster of Differentiation 8 (CD8) T Cell Populations
Cluster of differentiation 3 (CD3)+cluster of differentiation 4 (CD4)+ and CD3+CD8+ T cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count.
Measured: 2 weeks, 1, 3, 6, 12 and 24 months post transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Oct 200731 Dec 2018

First posted23 Aug 2007 (estimated)
Study start30 Oct 2007
Primary completion14 Oct 2015
Study completion31 Dec 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (6)Papers the sponsor has linked to this study.
Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 92 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00520130
Sponsor's protocol ID: 070195
Other IDs: 07-C-0195
Status last verified: Feb 2019
First submitted: 21 Aug 2007
Last updated: 5 Mar 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Pavletic SZ, Martin P, Lee SJ, Mitchell S, Jacobsohn D, Cowen EW, Turner ML, Akpek G, Gilman A, McDonald G, Schubert M, Berger A, Bross P, Chien JW, Couriel D, Dunn JP, Fall-Dickson J, Farrell A, Flowers ME, Greinix H, Hirschfeld S, Gerber L, Kim S, Knobler R, Lachenbruch PA, Miller FW, Mittleman B, Papadopoulos E, Parsons SK, Przepiorka D, Robinson M, Ward M, Reeve B, Rider LG, Shulman H, Schultz KR, Weisdorf D, Vogelsang GB; Response Criteria Working Group. Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. Response Criteria Working Group report. Biol Blood Marrow Transplant. 2006 Mar;12(3):252-66. doi: 10.1016/j.bbmt.2006.01.008.
PubMed 16503494
Shaffer BC, Modric M, Stetler-Stevenson M, Arthur DC, Steinberg SM, Liewehr DJ, Fowler DH, Gale RP, Bishop MR, Pavletic SZ. Rapid complete donor lymphoid chimerism and graft-versus-leukemia effect are important in early control of chronic lymphocytic leukemia. Exp Hematol. 2013 Sep;41(9):772-8. doi: 10.1016/j.exphem.2013.04.015. Epub 2013 May 18.
PubMed 23689118
Pavletic SZ, Lee SJ, Socie G, Vogelsang G. Chronic graft-versus-host disease: implications of the National Institutes of Health consensus development project on criteria for clinical trials. Bone Marrow Transplant. 2006 Nov;38(10):645-51. doi: 10.1038/sj.bmt.1705490. Epub 2006 Sep 18.
PubMed 16980994
Hardy NM, Fellowes V, Rose JJ, Odom J, Pittaluga S, Steinberg SM, Blacklock-Schuver B, Avila DN, Memon S, Kurlander RJ, Khuu HM, Stetler-Stevenson M, Mena E, Dwyer AJ, Levine BL, June CH, Reshef R, Vonderheide RH, Gress RE, Fowler DH, Hakim FT, Bishop MR. Costimulated tumor-infiltrating lymphocytes are a feasible and safe alternative donor cell therapy for relapse after allogeneic stem cell transplantation. Blood. 2012 Mar 22;119(12):2956-9. doi: 10.1182/blood-2011-09-378398. Epub 2012 Jan 30.
PubMed 22289893
Holtzman NG, Curtis LM, Salit RB, Shaffer BC, Pirsl F, Ostojic A, Steinberg SM, Schulz E, Wilder JS, Hughes TE, Rose J, Memon S, Korngold R, Gea-Banacloche JC, Fowler DH, Hakim FT, Gress RE, Bishop MR, Pavletic SZ. High-dose alemtuzumab and cyclosporine vs tacrolimus, methotrexate, and sirolimus for chronic graft-versus-host disease prevention. Blood Adv. 2024 Aug 27;8(16):4294-4310. doi: 10.1182/bloodadvances.2023010973.
PubMed 38669315
Assmann JC, Farthing DE, Saito K, Maglakelidze N, Oliver B, Warrick KA, Sourbier C, Ricketts CJ, Meyer TJ, Pavletic SZ, Linehan WM, Krishna MC, Gress RE, Buxbaum NP. Glycolytic metabolism of pathogenic T cells enables early detection of GVHD by 13C-MRI. Blood. 2021 Jan 7;137(1):126-137. doi: 10.1182/blood.2020005770.
PubMed 32785680

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 5 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase II Trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation Using 8/8 and 7/8 HLA-matched Unrelated Donors and Utilizing Two Graft-versus-Host Disease Prophylaxis Regimens for the Treatment of Leukemias, Lymphomas, and Pre-malignant Blood Disorders
ClinicalTrials.gov ID: NCT00520130
Acronym / sponsor ID: 070195
Conditions: Myelodysplastic Syndrome, Hodgkin's Lymphoma, Non-Hodgkin's Disease, Acute Leukemia, Multiple Myeloma
Keywords: Unrelated Donors, Reduced Intensity Stem Cell Transplant, Leukemia, Lymphoma, Allogeneic Stem Cell Transplant, Myelodysplastic Syndrome, Multiple Myeloma
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 92 participants (actual)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: 30 Oct 2007 (actual)
Primary completion: 14 Oct 2015 (actual)
Study completion: 31 Dec 2018 (actual)
First posted: 23 Aug 2007 (estimated)
Results: Posted 24 Aug 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Background:

Objectives:

Eligibility:

People 18 to 74 years of age with advanced or high-risk cancers of the blood and immune system who do not have a suitable HLA-matched sibling.

Design:

All patients receive chemotherapy before transplant to treat the cancer and suppress immune function.

All patients receive a conditioning regimen of cyclophosphamide for 4 days and fludarabine for 4 days before SCT to prepare for the transplant.

Patients are randomly assigned to one of two combination drug treatments to prevent GHVD as follows:

Group 1: Tacrolimus starting 3 days before SCT and continuing for 6 months, plus methotrexate on days 1, 3, 6, and 11 post-SCT, plus sirolimus starting 3 days before the SCT and continues for 6 months following SCT.
Group 2: Alemtuzumab for 4 days starting 8 days before SCT, plus cyclosporine starting 1 day before SCT and continuing for 6 months.

Patients receive the donors stem cells and immune cells 2 days after completing the conditioning regimen.

A skin biopsy, oral mucosa biopsy, and saliva collection are done to study chronic GVHD.

...

Detailed description

Background:

The major limitations to the broader applicability of allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of malignancies are lack of suitable donors and therapy-related toxicities which include delayed and incomplete immune reconstitution and graft-versus-host disease (GVHD). Based on the theory that the rapid establishment of donor chimerism was essential for an optimal graft-versus-tumor effect, we have employed a strategy of targeted immune depleting chemotherapy prior to reduced-intensity allogeneic HSCT. It is our intent to investigate this approach in the setting of human leukocyte-antigen (HLA)-matched unrelated donors in a pilot manner.
A clearly superior GVHD prophylaxis regimen has not been established in the unrelated donor transplant setting. The best results that have been reported are with the combination of alemtuzumab plus cyclosporine [AC] and the combination of tacrolimus, methotrexate, and sirolimus [TMS]. These two regimens work by mechanisms which are biologically distinct and potentially have markedly different effects upon immune reconstitution that have not been well studied. In addition, neither of these regimens has been assessed for their effects on chronic GVHD using the National Institutes of Health (NIH) Consensus Conference Criteria. It is our intent to study the effects that these two regimens have on immune reconstitution and chronic GVHD in the setting sequential targeted immune-depleting chemotherapy and reduced-intensity allogeneic HSCT from HLA-matched unrelated donors.

Objectives:

Primary objectives:

to assess the effects of two biologically distinct GVHD prophylaxis regimens, TMS and AC, on immune reconstitution in patients receiving targeted-immune depletion and reduced-intensity allogeneic HSCT from HLA-matched unrelated donors. As part of a comprehensive assessment of immune reconstitution, the primary immunologic endpoint will be the determination of cluster of differentiation 4 (CD4)+ T cell receptor V BETA repertoire by complementarity determining region 3 (CDR3) spectratyping at 3 months post-transplant.
to assess overall safety of these two regimens in this setting, as determined by engraftment, acute GVHD, early and late treatment-related mortality, and overall survival.
to determine and monitor incidence, organ severity and overall severity of chronic GVHD prospectively using the newly developed NIH Consensus Conference diagnosis and staging criteria and preliminarily validate those tools for use in clinical practice and trials.

Secondary objectives include further assessment of immune reconstitution, study of engraftment kinetics, and assessment of those patients who receive higher doses of anthracyclines for long and short term toxicities

Eligibility:

Adults (18-74 years) with advanced or high risk hematologic malignancies including acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL), non-hodgkin lymphoma (NHL), hodgkin lymphoma (HL), chronic myelogenous leukemia (CML), multiple myeloma, and myeloproliferative disorder (MPD) who lack a suitable HLA matched sibling.
An unrelated donor matched at a minimum of 7 of 8 alleles (HLA-A,-B,-C, and DRB1) by high resolution typing, identified through the National Marrow Donor Program.
Life expectancy of at least 3 months, Eastern Cooperative Oncology Group (ECOG) less than or equal to 2 and relatively normal major organ functions.

Design:

Patients will receive disease-specific induction chemotherapy (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH-fludarabine (F)/rituximab (R) or fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG)) prior to transplant for disease control and immune depletion. If disease is controlled (greater than partial response (PR)) and immune depletion objectives have been met, patients may forgo induction chemotherapy and move forward to the transplant conditioning regimen.
All patients will receive an identical conditioning regimen consisting of cyclophosphamide 1200 mg/m(2)/day intravenous (IV) for 4 days and fludarabine 30 mg/m(2)/day for 4 days.
Patients will be stratified according to degree of HLA-match and randomized at the time of enrollment to one of two GHVD prophylaxis regimens:
Group 1: Tacrolimus starting 3 days before stem cell transplant (SCT), and continuing for 6 months, plus methotrexate on days 1, 3, 6, and 11 post-SCT, plus sirolimus starting 3 days before the SCT and continues for 6 months following SCT.
Group 2: Alemtuzumab for 4 days starting 8 days before SCT, plus cyclosporine starting 1 day before SCT and continuing for 6 months.
A maximum of 105 patients will be enrolled and randomly assigned to the two arms in order to yield 44 patients per arm (88 total patients) who are able to be evaluated for development of severe chronic GVHD.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
A - Tacrolimus, methotrexate, sirolimus (TMS) Arm	Experimental	Biological: Rituximab, Drug: Allogenic stem cell transplant (ASCT), Drug: Conditioning Chemotherapy, Drug: TMS, Drug: FLAG, Drug: EPOCH-FTMS Arm
B - Cyclosporine (AC) Arm	Experimental	Biological: Rituximab, Drug: Cyclosporine, Drug: Allogenic stem cell transplant (ASCT), Drug: Conditioning Chemotherapy, Drug: FLAG, Drug: EPOCH-F, Biological: AlemtuzumabAC Arm

Who may qualify

Ages: 18 to 74 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (0 listed)

Key exclusion criteria (2 listed)

Human immunodeficiency virus (HIV) infection. There is theoretical concern that the degree of immune suppression associated with the treatment may result in progression of HIV infection.
Pregnant or lactating. Patients of childbearing potential must use an effective method of contraception. The effects of the chemotherapy, the subsequent transplant and the medications used after the transplant are highly likely to be harmful to a fetus. The effects upon breast milk are also unknown and may be harmful to the infant.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RituximabAlso: RituxanRituximab: 375 mg/m(2) intravenous (IV), day 1 for patients with cluster of differentiation 20 (CD20)-positive disease.	Biological	A - Tacrolimus, methotrexate, sirolimus (TMS) Arm, B - Cyclosporine (AC) Arm
CyclosporineAlso: NeoralCyclosporine: IV over 2 hours or orally every 12 hours on days -1 to 100, followed by a taper if graft versus host disease (GVHD) does not develop.	Drug	B - Cyclosporine (AC) Arm
Allogenic stem cell transplant (ASCT)Allogenic stem cell transplant	Drug	A - Tacrolimus, methotrexate, sirolimus (TMS) Arm, B - Cyclosporine (AC) Arm
Conditioning ChemotherapyFludarabine:30 mg/m(2) per day IV infusion over 30 minutes, daily. On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m(2) per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna: 1200 mg/m(2) per day IV infusion, Daily on days 6, -5,-4, and -3	Drug	A - Tacrolimus, methotrexate, sirolimus (TMS) Arm, B - Cyclosporine (AC) Arm
TMSAlso: PrografTacrolimus: starting day -3 before transplant, given initially at 0.02 mg/kg/day CIV. Continue IV and then switch to an equivalent oral dose (when patient taking po) titrated for a goal level of 5 to 10 ng/ml; Sirolimus: given as an initial loading dose of 12 mg p.o. on day -3 pre-transplant, 4 mg starting day -2 pre-transplant and titrated for levels 3-12 ng/ml; Methotrexate 5 mg/m2 IV on days +1, +3, +6, and +11 post-transplant. Tacrolimus and sirolimus will be tapered at day +63, day +119 and day +180 post-transplant as tolerated.	Drug	A - Tacrolimus, methotrexate, sirolimus (TMS) Arm
FLAGAlso: Fludarabine+high-dose cytarabine+G-CSF (Filgrastim))Fludarabine:25 mg/m(2) per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m(2) IV over 4 hours,on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day subcutaneous (SC) beginning 24 hours PRIOR to initiation of chemotherapy	Drug	A - Tacrolimus, methotrexate, sirolimus (TMS) Arm, B - Cyclosporine (AC) Arm
EPOCH-FFludarabine:25 mg/m(2) per day IV infusion over 30 minutes, daily on days 1-4 Etoposide :50 mg/m(2) per day continuous IV infusion over 24 hours on days 1-4 Doxorubicin:10 mg/m(2)/day CIV, days 1-4 Vincristine:0.4 mg/m(2) per day continuous IV infusion over 24 hours daily on days 1-4 Cyclophosphamide:750 mg/m(2) IV infusion over 30 minutes on day 5	Drug	A - Tacrolimus, methotrexate, sirolimus (TMS) Arm, B - Cyclosporine (AC) Arm
AlemtuzumabAlso: CampathAlemtuzumab:20 mg/day IV over 8 h on days 8 to 4 pre-transplant.	Biological	B - Cyclosporine (AC) Arm

Primary outcome

Percentage of Participants With Grade II-IV Acute Graft Versus Host Disease (GVHD)
Time frame: 6 months
Acute GVHD is assessed by the 1994 Consensus Conference on Acute GVHD Grading criteria. See Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995; 15:825-8., for grading criteria.
Percentage of Participants With Chronic Graft Versus Host Disease (cGVHD)
Time frame: 2 years post transplant
Chronic GVHD is assessed by the 2005 Chronic GVHD Consensus Project. First the individual organ scoring is done, and then based on that the Global score is determined (mild-moderate-severe). See Citation: Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11:945-56., for grading criteria.
Recovery of Naïve Cluster of Differentiation 4 (CD4) T Cells
Time frame: Recipient recovery at 6, 12 and 24 months post transplant
The percentage of C-C motif chemokine receptor 7 (CCR7)+CD45RA+ naïve T cells within the CD4 T cell populations was determined by flow cytometry.
Recovery of Naïve Cluster of Differentiation 8 (CD8) T Cells
Time frame: Recipient recovery at 6, 12 and 24 months post transplant
The percentage of CCR7+CD45RA+ naïve T cells within the CD4 and CD8 T cell populations was determined by flow cytometry.
Changes in Cluster of Differentiation 4 (CD4) T Cell Receptor Vbeta Repertoire
Time frame: Donor at time of collection and recipient at 1, 3, 6 and 12 months post transplant
Ribonucleic acid (RNA) was extracted from sorted CD4 and cluster of differentiation 8 (CD8) T cells and analyzed for Vbeta repertoire by nested polymerase chain reaction (PCR) analysis using Vbeta family specific primers and a labeled constant region primer (spectratyping). The receptor repertoire diversity was calculated from spectratyping data by creating a normal standard for repertoire diversity from healthy normal controls and assessing the divergence of individual patient's T cell receptor repertoire from these standard normal donor values. In this Vbeta repertoire divergence index, lower numbers are consistent with a more normal highly diverse repertoire, and high numbers represent a highly skewed, oligoclonal repertoire. The assay is described in Memon SA et al, J Immunol Methods, 2012, 375: 84-92. The repertoire diversity of the CD4 and CD8 T cells of the donor infusion is shown for comparison.
Changes in CD8 T Cell Receptor Vbeta Repertoire
Time frame: Donor at time of collection and recipient at 1, 3, 6 and 12 months post transplant
Ribonucleic acid (RNA) was extracted from sorted CD4 and cluster of differentiation 8 (CD8) T cells and analyzed for Vbeta repertoire by nested polymerase chain reaction (PCR) analysis using Vbeta family specific primers and a labeled constant region primer (spectratyping). The receptor repertoire diversity was calculated from spectratyping data by creating a normal standard for repertoire diversity from healthy normal controls and assessing the divergence of individual patient's T cell receptor repertoire from these standard normal donor values. In this Vbeta repertoire divergence index, lower numbers are consistent with a more normal highly diverse repertoire, and high numbers represent a highly skewed, oligoclonal repertoire. The assay is described in Memon SA et al, J Immunol Methods, 2012, 375: 84-92. The repertoire diversity of the CD4 and CD8 T cells of the donor infusion is shown for comparison.

12 secondary outcomes

Percentage of Participants With Grade III-IV Acute Graft Versus Host Disease (GVHD)
Time frame: 6 months
Toxicities
Time frame: 103 months and 22 days
Days to Engraftment of Neutrophils
Time frame: 2 years
Days to Engraftment of Platelets
Time frame: 2 years
Days to Engraftment of Lymphocytes
Time frame: 2 years
Overall Survival
Time frame: Patients were followed for an average of up to 5 years.
Early Treatment Related Mortality
Time frame: Less than or equal to 28 days after transplantation
Percentage of Participants With Late Treatment Related Mortality
Time frame: Greater than 28 days after transplantation
Decline in Homeostatic Cytokine Interleukin 7 (IL-7) Post-Transplant
Time frame: Day 0, 1 week and 2 weeks
Immune Reconstitution of Normal Killer (NK) Cells
Time frame: 2 weeks, and 1, 3, 6, 12, and 24 months post transplant
Immune Reconstitution of Cluster of Differentiation 4 (CD4) T Cell Populations
Time frame: 2 weeks, and 1, 3, 6, 12 and 24 months post transplant
Immune Reconstitution of Cluster of Differentiation 8 (CD8) T Cell Populations
Time frame: 2 weeks, 1, 3, 6, 12 and 24 months post transplant

Results and safety

Results posted to the registry on 24 Aug 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	44	39
B - Cyclosporine (AC) Arm	45	44

Primary outcome: Percentage of Participants With Grade II-IV Acute Graft Versus Host Disease (GVHD)

Time frame: 6 months. Number (95% Confidence Interval). Unit: percentage of participants

Measure	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm n = 39	B - Cyclosporine (AC) Arm n = 42
Value	42 (26 to 57)	38 (23 to 53)

Population analysed: 2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.

Primary outcome: Percentage of Participants With Chronic Graft Versus Host Disease (cGVHD)

Time frame: 2 years post transplant. Number (95% Confidence Interval). Unit: percentage of participants

Measure	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm n = 39	B - Cyclosporine (AC) Arm n = 42
Moderate or Severe cGVHD	50 (32 to 65)	12 (4 to 25)
Severe cGVHD	28 (14 to 43)	5 (1 to 15)

Population analysed: 2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.

Primary outcome: Recovery of Naïve Cluster of Differentiation 4 (CD4) T Cells

Time frame: Recipient recovery at 6, 12 and 24 months post transplant. Median (Full Range). Unit: % of naive (CCR7+CD45RA+) CD4 Cells

Measure	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm n = 28	B - Cyclosporine (AC) Arm n = 28
6 mo (TMS=28; AC= 28)	24 (2 to 65)	1 (0 to 22)
12 mo (TMS=25; AC= 21)	22 (5 to 48)	7 (0 to 42)
24 mo (TMS=18; AC= 13)	20 (4 to 60)	25 (1 to 60)

Population analysed: A few measurements were missed, one patient was not evaluable for technical reasons and removed from the analysis, but most of the decline was due to patients that had gone off study.

Primary outcome: Recovery of Naïve Cluster of Differentiation 8 (CD8) T Cells

Time frame: Recipient recovery at 6, 12 and 24 months post transplant. Median (Full Range). Unit: % of naive (CCR7+CD45RA+) CD8 Cells

Measure	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm n = 28	B - Cyclosporine (AC) Arm n = 28
6 mo (TMS=28; AC= 28)	20 (0 to 75)	3 (0 to 78)
12 mo (TMS=25; AC= 21)	17 (7 to 79)	6 (0 to 79)
24 mo (TMS=18; AC= 13)	16 (1 to 60)	6 (0 to 65)

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: 103 months and 22 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	36 of 44 (81.8%)	43 of 44 (97.7%)	8 of 44
B - Cyclosporine (AC) Arm	41 of 45 (91.1%)	42 of 45 (93.3%)	19 of 45

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 16503494Pavletic SZ, Martin P, Lee SJ, Mitchell S, Jacobsohn D, Cowen EW, Turner ML, Akpek G, Gilman A, McDonald G, Schubert M, Berger A, Bross P, Chien JW, Couriel D, Dunn JP, Fall-Dickson J, Farrell A, Flowers ME, Greinix H, Hirschfeld S, Gerber L, Kim S, Knobler R, Lachenbruch PA, Miller FW, Mittleman B, Papadopoulos E, Parsons SK, Przepiorka D, Robinson M, Ward M, Reeve B, Rider LG, Shulman H, Schultz KR, Weisdorf D, Vogelsang GB; Response Criteria Working Group. Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. Response Criteria Working Group report. Biol Blood Marrow Transplant. 2006 Mar;12(3):252-66. doi: 10.1016/j.bbmt.2006.01.008.
Background: PubMed 23689118Shaffer BC, Modric M, Stetler-Stevenson M, Arthur DC, Steinberg SM, Liewehr DJ, Fowler DH, Gale RP, Bishop MR, Pavletic SZ. Rapid complete donor lymphoid chimerism and graft-versus-leukemia effect are important in early control of chronic lymphocytic leukemia. Exp Hematol. 2013 Sep;41(9):772-8. doi: 10.1016/j.exphem.2013.04.015. Epub 2013 May 18.
Background: PubMed 16980994Pavletic SZ, Lee SJ, Socie G, Vogelsang G. Chronic graft-versus-host disease: implications of the National Institutes of Health consensus development project on criteria for clinical trials. Bone Marrow Transplant. 2006 Nov;38(10):645-51. doi: 10.1038/sj.bmt.1705490. Epub 2006 Sep 18.
Background: PubMed 22289893Hardy NM, Fellowes V, Rose JJ, Odom J, Pittaluga S, Steinberg SM, Blacklock-Schuver B, Avila DN, Memon S, Kurlander RJ, Khuu HM, Stetler-Stevenson M, Mena E, Dwyer AJ, Levine BL, June CH, Reshef R, Vonderheide RH, Gress RE, Fowler DH, Hakim FT, Bishop MR. Costimulated tumor-infiltrating lymphocytes are a feasible and safe alternative donor cell therapy for relapse after allogeneic stem cell transplantation. Blood. 2012 Mar 22;119(12):2956-9. doi: 10.1182/blood-2011-09-378398. Epub 2012 Jan 30.
Derived from this study: PubMed 38669315Holtzman NG, Curtis LM, Salit RB, Shaffer BC, Pirsl F, Ostojic A, Steinberg SM, Schulz E, Wilder JS, Hughes TE, Rose J, Memon S, Korngold R, Gea-Banacloche JC, Fowler DH, Hakim FT, Gress RE, Bishop MR, Pavletic SZ. High-dose alemtuzumab and cyclosporine vs tacrolimus, methotrexate, and sirolimus for chronic graft-versus-host disease prevention. Blood Adv. 2024 Aug 27;8(16):4294-4310. doi: 10.1182/bloodadvances.2023010973.
Derived from this study: PubMed 32785680Assmann JC, Farthing DE, Saito K, Maglakelidze N, Oliver B, Warrick KA, Sourbier C, Ricketts CJ, Meyer TJ, Pavletic SZ, Linehan WM, Krishna MC, Gress RE, Buxbaum NP. Glycolytic metabolism of pathogenic T cells enables early detection of GVHD by 13C-MRI. Blood. 2021 Jan 7;137(1):126-137. doi: 10.1182/blood.2020005770.
NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Steven Z Pavletic, M.D. principal investigator

National Cancer Institute (NCI)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Grade II-IV Acute Graft Versus Host Disease (GVHD) (time frame: 6 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00520130, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2019.