Accelerated Phase of DiseasePhase 2NCT00003145

Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Older Patients With Chronic Myeloid Leukemia

A Phase 2 study testing Fludarabine Phosphate, Total-Body Irradiation and Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation in people with Accelerated Phase of Disease and Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive, run by Fred Hutchinson Cancer Center at 8 sites in 3 countries.

Completed

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

Official record

Search all trials

Trial summary

Who is it for?: Ages Up to 74 years
Conditions the study is for: Accelerated Phase of Disease, Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Myelogenous Leukemia, BCR-ABL1 Positive
What is being tested?: Fludarabine Phosphate, Total-Body Irradiation and Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 8 sitesin 3 countries
Study dates: Aug 1997to Mar 2005
Phase: Phase 2
Are there results?: None posted in the registry

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 Up to 74 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Patients with Philadelphia chromosome positive (Ph+) CML in first and second chronic and first accelerated phases
Patients =< 65 years old who are at high risk of regimen related toxicity through pre-existing chronic disease affecting liver, lungs, and/or heart, or others who wish to be treated on this protocol, will be considered on a case-by-case basis; transplants should be approved for these inclusion criteria by both the participating institutions' patient review committees such as the Patient Care Conference (PCC) at the Fred Hutchinson Cancer Research Center (FHCRC) and by the principal investigators at the collaborating centers; patients =< 65 years of age who have received previous high-dose transplantation do not require patient review committee approvals; all children < 12 years must be discussed with the FHCRC principal investigator (PI) (Brenda Sandmaier, MD 206-667-4961) prior to registration
HLA genotypically identical related donor willing to undergo leukapheresis initially for collection of peripheral blood stem cell (PBSC) and subsequently for collection of peripheral blood mononuclear cell (PBMC)
Patients treated with alpha interferon must have discontinued drug at least 1 month prior to transplant
DONOR: HLA genotypically identical family member (excluding identical twins)
DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis
DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)

Who cannot join

Patients who are human immunodeficiency virus positive (HIV+)
GROUP 1: (PATIENTS AGED > 65 AND < 75 YEARS)
Patients unwilling to use contraceptive techniques during and for 12 months following treatment
Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with CML
Patients in an interferon induced complete or partial cytogenetic remission
Organ dysfunction:

Show all 31Show fewer

Patients with renal failure are eligible, however patients with renal compromise (Serum creatinine greater than 2.0) will likely have further compromise in renal function and may require hemodialysis (which may be permanent) due to the need to maintain adequate serum cyclosporine levels
Cardiac ejection fraction < 40%; ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease
Diffusing capacity of the lung for carbon monoxide (DLCO) < 50% of predicted
Liver function tests including total bilirubin, serum glutamic pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) > 2x the upper limit of normal unless proven to be due to the malignancy
Karnofsky score < 70
Patients with poorly controlled hypertension
GROUP 2 (PATIENTS AGED =< 65)
Patients who are HIV+
Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with CML
Females who are pregnant
Patients unwilling to use contraceptive techniques during and for 12 months following treatment
Patients in an interferon induced complete or partial cytogenetic remission
Organ dysfunction:
Patients with renal failure are eligible, however patients with renal compromise (Serum creatinine greater than 2.0) will likely have further compromise in renal function and may require hemodialysis (which may be permanent) due to the need to maintain adequate serum cyclosporine levels
Cardiac ejection fraction < 40% or a history of congestive heart failure; ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease
Severe defects in pulmonary function testing as defined by the pulmonary consultant (defects are currently categorized as mild, moderate and severe) or receiving supplementary continuous oxygen; DLCO < 50% of predicted
Liver function tests: total bilirubin > 2x the upper limit of normal, SGPT and SGOT 4x the upper limit of normal
Karnofsky score < 50
Patients with poorly controlled hypertension
DONOR: Age less than 12 years
DONOR: Pregnancy
DONOR: Infection with HIV
DONOR: Inability to achieve adequate venous access
DONOR: Known allergy to G-CSF
DONOR: Current serious systemic illness

Trial locations and contacts

8 sites in 3 countries.

Country

City, postcode or hospital

8 sites in 3 countries

United States6 sites

Baylor University Medical Center
Dallas, Texas, 75246
University of Colorado
Denver, Colorado, 80217-3364
City of Hope Medical Center
Duarte, California, 91010
VA Puget Sound Health Care System
Seattle, Washington, 98101
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109
Stanford University Hospitals and Clinics
Stanford, California, 94305

Other trials in United States

Germany1 site

Universitaet Leipzig
Leipzig, D-04103

Other trials in Germany

Italy1 site

University of Torino
Torino, 10126

Other trials in Italy

About this study

Official title: Induction of Mixed Hematopoietic Chimerism Using Fludarabine, Low Dose TBI , PBSC Infusion and Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil to be Followed by Donor Lymphocyte Infusion In Patients With Chronic Myeloid Leukemia in Chronic and Accelerated Phases: A Multi-center Study

This clinical trial studies fludarabine phosphate, low-dose total-body irradiation, and peripheral blood stem cell transplant followed by donor lymphocyte infusion in treating older patients with chronic myeloid leukemia. Giving chemotherapy and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.

Read the detailed description

PRIMARY OBJECTIVES:

To determine if mixed hematopoietic chimerism can be safely established using a non-myeloablative conditioning regimen in patients > 65 years of age with chronic myeloid leukemia (CML) in chronic or accelerated phase who have human leukocyte antigen (HLA) identical related donors.

II. To determine if mixed chimerism, established with non-myeloablative conditioning regimens, can be converted to full donor hematopoietic chimerism by infusions of donor lymphocytes (DLI), and thereby produce an immunologic cure of the malignancy.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo low-dose total-body irradiation (TBI) on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) or IV BID or thrice daily (TID) on days -3 to 56 with taper to day 77 or 180, and mycophenolate mofetil PO or IV BID on days 0-27.

DLI: At least 2 weeks after completion of immunosuppression, patients with > 5% donor cluster of differentiation (CD)3+ T cells and no evidence of graft-versus-host disease (GVHD) receive donor lymphocytes IV over 30 minutes. Patients may receive up to 3 DLIs at increasing cell doses in the absence of GVHD.

After completion of study treatment, patients are followed up periodically for 5 years.

Conditions: Accelerated Phase of Disease, Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Phase of Disease, Recurrent Disease
Being tested: Fludarabine Phosphate, Total-Body Irradiation, Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation, Peripheral Blood Stem Cell Transplantation, Cyclosporine
Medical subject headings: Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Recurrence

What participants receive

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

Fludarabine PhosphateDrug
Also called 2-F-ara-AMP, Beneflur, SH T 586
Given IV
Total-Body IrradiationRadiation
Also called TBI, Total Body Irradiation, Whole-Body Irradiation
Undergo TBI
Nonmyeloablative Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplantation, NST
Undergo allogeneic PBSCT
Peripheral Blood Stem Cell TransplantationProcedure or surgery
Also called PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation
Undergo allogeneic PBSCT
CyclosporineDrug
Also called 27-400, CsA, Neoral, OL 27-400
Given PO or IV
Mycophenolate MofetilDrug
Also called Cellcept, MMF
Given PO or IV
Therapeutic Allogeneic LymphocytesBiological
Also called Allogeneic Lymphocytes, ALLOLYMPH, Tumor-Derived Lymphocyte
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies

Study groups in NCT00003145
Study group	Role	What they receive
Treatment (chemotherapy, TBI, PBSCT, DLI)	Experimental	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV BID or TID on days -3 to 56 with taper to day 77 or 180, and mycophenolate mofetil PO or IV BID on days 0-27. DLI: At least 2 weeks after completion of immunosuppression, patients with > 5% donor CD3+ T cells and no evidence of GVHD receive donor lymphocytes IV over 30 minutes. Patients may receive up to 3 DLIs at increasing cell doses in the absence of GVHD. Receives: Drug: Fludarabine Phosphate; Radiation: Total-Body Irradiation; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Cyclosporine; Drug: Mycophenolate Mofetil; Biological: Therapeutic Allogeneic Lymphocytes; Other: Laboratory Biomarker Analysis

What is being measured

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

Safety of establishing mixed chimerism using this non-lethal conditioning regimen, in terms of development of GVHD, myelosuppression, infections, and treatment-related mortality
All unexpected toxicities will be summarized and reported.
Measured: Within the first 65 days
Proportion of patients who successfully establish mixed chimerism (evidence of donor engraftment) and the proportion who convert to full donor chimeras among those who were mixed
Estimated and corresponding confidence intervals presented. Mixed chimerism is detection of donor T cells (CD3+) and granulocytes (CD33+), as proportion of total T cell and granulocyte population of > 5% and < 95% in peripheral blood. Full donor chimerism is > 95% donor CD3+ T cells. Increasing donor chimerism is absolute increase of 20% of CD3+ T cells over chimerism evaluation of previous month. Decreasing donor chimerism is absolute decrease of 20% of CD3+ T cell chimerism over previous month. Low donor chimerism is < 40% CD3+ T cells after HSCT.
Measured: Day 28
Proportion of patients who successfully establish mixed chimerism (evidence of donor engraftment) and the proportion who convert to full donor chimeras among those who were mixed
Estimated and corresponding confidence intervals presented. Mixed chimerism is detection of donor T cells (CD3+) and granulocytes (CD33+), as proportion of total T cell and granulocyte population of > 5% and < 95% in peripheral blood. Full donor chimerism is > 95% donor CD3+ T cells. Increasing donor chimerism is absolute increase of 20% of CD3+ T cells over chimerism evaluation of previous month. Decreasing donor chimerism is absolute decrease of 20% of CD3+ T cell chimerism over previous month. Low donor chimerism is < 40% CD3+ T cells after HSCT.
Measured: Day 56

Secondary outcomes (9)

Proportion of patients experiencing a complete antileukemic response
Reported in a descriptive manner and confidence intervals will be presented for all estimates.
Measured: At 12 weeks after the final DLI
Proportion of patients experiencing GVHD
Reported in a descriptive manner and confidence intervals will be presented for all estimates.
Measured: Until day 90 after the last DLI
Proportion of patients experiencing non-relapse mortality
Reported in a descriptive manner and confidence intervals will be presented for all estimates.
Measured: Within 65 days of transplant
Incidence of myelosuppression after initial PBSC infusion
Defined as absolute neutrophil count [ANC] < 500 for > 2 days, platelets < 20,000 for > 2 days.
Measured: Until 2 months post-transplant
Incidence of aplasia after DLI
Measured: Until 2 months post-transplant
Incidence of grades 2-4 acute GVHD after DLI
Measured: Until day 90 after the last DLI
Incidence of grades 2-4 acute GVHD after PBSC infusion
Measured: Until day 90 after the last DLI
Incidence of grade chronic extensive GVHD after DLI
Measured: At 1 year
Dose of CD3+ cells required to convert mixed to full lymphoid chimeras
Measured: Day 56

Timeline

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

Aug 1997Mar 2005

First posted27 Jan 2003 (estimated)
Study startAug 1997
Primary completionMar 2005

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Accelerated Phase of DiseaseStudies of the same condition, open and under way.
More trials run by Fred Hutchinson Cancer CenterThe 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 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00003145
Sponsor's protocol ID: 1209.00
Other IDs: NCI-2012-00579, 1209.00, P30CA015704
Status last verified: Jan 2020
First submitted: 1 Nov 1999
Last updated: 10 Jan 2020
Results posted: No
Data monitoring committee: Yes

Publications

Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.
PubMed 32499241

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

Active, not recruitingPhase 1
Hypofractionated Accelerated Pelvic Nodal Radiotherapy (GCC 2048)
Prostate Cancer, Prostate Adenocarcinoma
Not yet recruitingPhase 2/3
A Randomized Trial of Standard vs. Hypofractionated Accelerated Radiotherapy for Progression in Limited-Stage Small Cell Lung Cancer
Limited Stage Small-Cell Lung Cancer
RecruitingPhase 2
Personalized NK Cell Therapy in CBT
Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Biphenotypic Leukemia
RecruitingPhase 1/2
Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT)
Acute Myeloid Leukemia, Acute Lymphoid Leukemia
RecruitingObservational study
Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer
Chronic Myeloproliferative Disorders, Leukemia

All Accelerated Phase of Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Induction of Mixed Hematopoietic Chimerism Using Fludarabine, Low Dose TBI , PBSC Infusion and Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil to be Followed by Donor Lymphocyte Infusion In Patients With Chronic Myeloid Leukemia in Chronic and Accelerated Phases: A Multi-center Study
ClinicalTrials.gov ID: NCT00003145
Acronym / sponsor ID: 1209.00
Conditions: Accelerated Phase of Disease, Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Phase of Disease, Recurrent Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: Fred Hutchinson Cancer CenterUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: Aug 1997
Primary completion: Mar 2005 (actual)
First posted: 27 Jan 2003 (estimated)
Results: Not posted in the source record

Clinical summary

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

Detailed description

PRIMARY OBJECTIVES:

To determine if mixed hematopoietic chimerism can be safely established using a non-myeloablative conditioning regimen in patients > 65 years of age with chronic myeloid leukemia (CML) in chronic or accelerated phase who have human leukocyte antigen (HLA) identical related donors.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo low-dose total-body irradiation (TBI) on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0.

After completion of study treatment, patients are followed up periodically for 5 years.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (chemotherapy, TBI, PBSCT, DLI)	Experimental	Drug: Fludarabine Phosphate, Radiation: Total-Body Irradiation, Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation, Procedure: Peripheral Blood Stem Cell Transplantation, Drug: Cyclosporine, Drug: Mycophenolate Mofetil, Biological: Therapeutic Allogeneic Lymphocytes, Other: Laboratory Biomarker AnalysisCONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV BID or TID on days -3 to 56 with taper to day 77 or 180, and mycophenolate mofetil PO or IV BID on days 0-27. DLI: At least 2 weeks after completion of immunosuppression, patients with > 5% donor CD3+ T cells and no evidence of GVHD receive donor lymphocytes IV over 30 minutes. Patients may receive up to 3 DLIs at increasing cell doses in the absence of GVHD.

Who may qualify

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

Key inclusion criteria (7 listed)

Patients with Philadelphia chromosome positive (Ph+) CML in first and second chronic and first accelerated phases
Patients =< 65 years old who are at high risk of regimen related toxicity through pre-existing chronic disease affecting liver, lungs, and/or heart, or others who wish to be treated on this protocol, will be considered on a case-by-case basis; transplants should be approved for these inclusion criteria by both the participating institutions' patient review committees such as the Patient Care Conference (PCC) at the Fred Hutchinson Cancer Research Center (FHCRC) and by the principal investigators at the collaborating centers; patients =< 65 years of age who have received previous high-dose transplantation do not require patient review committee approvals; all children < 12 years must be discussed with the FHCRC principal investigator (PI) (Brenda Sandmaier, MD 206-667-4961) prior to registration
HLA genotypically identical related donor willing to undergo leukapheresis initially for collection of peripheral blood stem cell (PBSC) and subsequently for collection of peripheral blood mononuclear cell (PBMC)
Patients treated with alpha interferon must have discontinued drug at least 1 month prior to transplant
DONOR: HLA genotypically identical family member (excluding identical twins)

Key exclusion criteria (31 listed)

Patients who are human immunodeficiency virus positive (HIV+)
GROUP 1: (PATIENTS AGED > 65 AND < 75 YEARS)
Patients unwilling to use contraceptive techniques during and for 12 months following treatment
Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with CML
Patients in an interferon induced complete or partial cytogenetic remission

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
Fludarabine PhosphateAlso: 2-F-ara-AMP, Beneflur, SH T 586Given IV	Drug	Treatment (chemotherapy, TBI, PBSCT, DLI)
Total-Body IrradiationAlso: TBI, Total Body Irradiation, Whole-Body IrradiationUndergo TBI	Radiation	Treatment (chemotherapy, TBI, PBSCT, DLI)
Nonmyeloablative Allogeneic Hematopoietic Stem Cell TransplantationAlso: Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplantation, NSTUndergo allogeneic PBSCT	Procedure or surgery	Treatment (chemotherapy, TBI, PBSCT, DLI)
Peripheral Blood Stem Cell TransplantationAlso: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell TransplantationUndergo allogeneic PBSCT	Procedure or surgery	Treatment (chemotherapy, TBI, PBSCT, DLI)
CyclosporineAlso: 27-400, CsA, Neoral, OL 27-400Given PO or IV	Drug	Treatment (chemotherapy, TBI, PBSCT, DLI)
Mycophenolate MofetilAlso: Cellcept, MMFGiven PO or IV	Drug	Treatment (chemotherapy, TBI, PBSCT, DLI)
Therapeutic Allogeneic LymphocytesAlso: Allogeneic Lymphocytes, ALLOLYMPH, Tumor-Derived LymphocyteGiven IV	Biological	Treatment (chemotherapy, TBI, PBSCT, DLI)
Laboratory Biomarker AnalysisCorrelative studies	Other	Treatment (chemotherapy, TBI, PBSCT, DLI)

Primary outcome

Safety of establishing mixed chimerism using this non-lethal conditioning regimen, in terms of development of GVHD, myelosuppression, infections, and treatment-related mortality
Time frame: Within the first 65 days
All unexpected toxicities will be summarized and reported.
Proportion of patients who successfully establish mixed chimerism (evidence of donor engraftment) and the proportion who convert to full donor chimeras among those who were mixed
Time frame: Day 28
Estimated and corresponding confidence intervals presented. Mixed chimerism is detection of donor T cells (CD3+) and granulocytes (CD33+), as proportion of total T cell and granulocyte population of > 5% and < 95% in peripheral blood. Full donor chimerism is > 95% donor CD3+ T cells. Increasing donor chimerism is absolute increase of 20% of CD3+ T cells over chimerism evaluation of previous month. Decreasing donor chimerism is absolute decrease of 20% of CD3+ T cell chimerism over previous month. Low donor chimerism is < 40% CD3+ T cells after HSCT.
Proportion of patients who successfully establish mixed chimerism (evidence of donor engraftment) and the proportion who convert to full donor chimeras among those who were mixed
Time frame: Day 56
Estimated and corresponding confidence intervals presented. Mixed chimerism is detection of donor T cells (CD3+) and granulocytes (CD33+), as proportion of total T cell and granulocyte population of > 5% and < 95% in peripheral blood. Full donor chimerism is > 95% donor CD3+ T cells. Increasing donor chimerism is absolute increase of 20% of CD3+ T cells over chimerism evaluation of previous month. Decreasing donor chimerism is absolute decrease of 20% of CD3+ T cell chimerism over previous month. Low donor chimerism is < 40% CD3+ T cells after HSCT.

9 secondary outcomes

Proportion of patients experiencing a complete antileukemic response
Time frame: At 12 weeks after the final DLI
Proportion of patients experiencing GVHD
Time frame: Until day 90 after the last DLI
Proportion of patients experiencing non-relapse mortality
Time frame: Within 65 days of transplant
Incidence of myelosuppression after initial PBSC infusion
Time frame: Until 2 months post-transplant
Incidence of aplasia after DLI
Time frame: Until 2 months post-transplant
Incidence of grades 2-4 acute GVHD after DLI
Time frame: Until day 90 after the last DLI
Incidence of grades 2-4 acute GVHD after PBSC infusion
Time frame: Until day 90 after the last DLI
Incidence of grade chronic extensive GVHD after DLI
Time frame: At 1 year
Dose of CD3+ cells required to convert mixed to full lymphoid chimeras
Time frame: Day 56

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2020.
Derived from this study: PubMed 32499241Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.

Related trials for Accelerated Phase of Disease

Active, not recruitingPhase 1
Hypofractionated Accelerated Pelvic Nodal Radiotherapy (GCC 2048)
Prostate Cancer, Prostate Adenocarcinoma
Not yet recruitingPhase 2/3
A Randomized Trial of Standard vs. Hypofractionated Accelerated Radiotherapy for Progression in Limited-Stage Small Cell Lung Cancer
Limited Stage Small-Cell Lung Cancer
RecruitingPhase 2
Personalized NK Cell Therapy in CBT
Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Biphenotypic Leukemia
RecruitingPhase 1/2
Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT)
Acute Myeloid Leukemia, Acute Lymphoid Leukemia
RecruitingObservational study
Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer
Chronic Myeloproliferative Disorders, Leukemia

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.

Brenda Sandmaier principal investigator

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

8 sites in 3 countries: 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 7 inclusion and 31 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 10 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Germany, Italy. 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 phase mean?

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Safety of establishing mixed chimerism using this non-lethal conditioning regimen, in terms of development of GVHD, myelosuppression, infections, and treatment-related mortality (time frame: Within the first 65 days). The study lists 3 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 NCT00003145, which also lists 1 linked publication.

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 10 Jan 2020.