CML (Chronic Myelogenous Leukemia)Phase 2NCT00467961
Stem Cell Transplantation for Patients With Cancers of the Blood
A Phase 2 study testing Miltenyi system in people with CML (Chronic Myelogenous Leukemia) and CLL (Chronic Lymphocytic Leukemia), run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
This study will try to improve the safety and effectiveness of stem cell transplant procedures in patients with cancers of the blood. It will use a special machine to separate immune cells (T cells) from the blood of both the donor and the patient and will use photodepletion, a laboratory procedure that selectively… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- CML (Chronic Myelogenous Leukemia), CLL (Chronic Lymphocytic Leukemia), AML (Acute Myelogenous Leukemia)
- What is being tested?
- Miltenyi system
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2007to Nov 2012
- Phase
- Phase 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Recipient Criteria:
- Diagnosed with one of the following hematological conditions:
- Chronic myelogenous leukemia (CML): chronic phase who have failed treatment with imatinib, have intolerance to imatinib, or who did not receive imatinib at therapeutic doses within the first 12 months from diagnosis; accelerated phase or blast transformation.
- Acute B-lymphoblastic leukemia (B-ALL): any of these categories: B-ALL in first remission with high-risk features (presenting leukocyte count greater than 100,000/cu mm, Karyotypes t9; 22, t4, t19, t11, biphenotypic leukemia), all second or subsequent remissions, primary induction failure, partially responding or untreated relapse.
- Acute myelogenous leukemia (AML): AML in first remission - except AML with good risk karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), AML t (8; 21). All AML in second or subsequent remission, primary induction failure and resistant relapse.
- Myelodysplastic syndromes (MDS): any of these categories - refractory anemia with transfusion dependence, refractory anemia with excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia, atypical MDS/myeloproliferative syndromes.
Show all 18Show fewer
- Myeloproliferative disorders including atypical (Ph negative) chronic myeloid and neutrophilic leukemias, progressing myelofibrosis, and polycythemia vera, essential thrombocythemia in transformation to acute leukemia or with progressive transfusion requirements or pancytopenia.
- Chronic lymphocytic leukemia refractory to fludarabine treatment and with bulky progressive disease or with thrombocytopenia (less than or equal to 100,000 /microl) or anemia (less than or equal to 10g/dl) not due to recent chemotherapy.
- Non-Hodgkin's lymphoma including Mantle cell lymphoma relapsing or refractory to standard of care treatments.
- Multiple myeloma, Waldenstroms macroglobulinemia, unresponsive or relapsed following standard of care treatments.
- Ages 18-75 years inclusive.
- HLA identical (6/6) related donor.
- Ability to comprehend the investigational nature of the study and provide informed consent.
- Donor Criteria:
- Related HLA identical (6/6) with recipient.
- Weight greater than or equal to 18 kg.
- Age greater than or equal to 2 or less than or equal to 80 years old.
- For adults: Ability to comprehend the investigational nature of the study and provide informed consent. For minors: Written informed consent from one parent or guardian and informed assent: The process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.
Who cannot join
- Recipient Criteria (any of the following):
- Malignant cells expressing a T cell phenotype (in particular T-ALL and T cell NHL).
- DLCO less than 65 percent predicted.
- Left ventricular ejection fraction less than 40 percent (evaluated by ECHO) or less than 30 percent (evaluated by MUGA).
- AST/SGOT greater than 10 times ULN (CTCAE grade IV v3.0).
- Bilirubin greater than 5 times ULN (CTCAE grade IV v3.0).
Show all 19Show fewer
- Creatinine greater than 4.5 times ULN (CTCAE grade IV v 3.0).
- HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-1/II) are not excluded from participation).
- Positive pregnancy test for women of childbearing age.
- Prior allogeneic stem cell transplantation.
- Estimated probability of surviving less than three months.
- Major anticipated illness or organ failure incompatible with survival from transplant.
- Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and informed consent impossible.
- Donor Criteria (any of the following):
- Pregnant or lactating.
- Unfit to receive filgrastim (G-CSF) and undergo apheresis (abnormal blood counts, history of stroke, uncontrolled hypertension).
- Sickling hemoglobinopathies including HbSS, HbAS, HbSC.
- HIV positive Donors who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) will be used at the discretion of the investigator following counseling and approval from the recipient.
- Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the donation of stem cells unlikely and informed consent impossible.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Selective Depletion of Alloreacting T Cells Using a Photodepletion Technique to Prevent GVHD After HLA-Matched Peripheral Blood Stem Cell Transplantation for Subjects With Hematologic Malignancies
This study will try to improve the safety and effectiveness of stem cell transplant procedures in patients with cancers of the blood. It will use a special machine to separate immune cells (T cells) from the blood of both the donor and the patient and will use photodepletion, a laboratory procedure that selectively kills cancer cells exposed to light. These special procedures may reduce the risk of graft-versus-host-disease (GVHD), a serious complication of stem cell transplants in which the donor's immune cells destroy the patient's healthy tissues, and at the same time may permit a greater graft-versus-leukemia effect, in which the donated cells fight any residual tumor cells that might remain in the body.
Patients between 18 and 75 years of age with a life-threatening disease of the bone marrow (acute or chronic leukemia, myelodysplastic syndrome, or myeloproliferative syndrome) may be eligible for this study. Candidates must have a family member who is a suitable tissue match.
Read the detailed description
Peripheral blood stem cell transplant research carried out by the NHLBI BMT Unit focus on approaches in transplant techniques designed to decrease graft versus host disease (GVHD), increase the graft-versus-leukemia (GVL) effect, and/or reduce the risk for post-transplant graft rejection or disease relapse.
Ex vivo selective depletion of alloreacting T cells, hereafter referred as selective depletion (SD), represents a translational strategy aiming to reduce severe GVHD whilst preserving GVL. We found that selectively depleted transplants are safe to administer and associated with less severe acute GVHD. This protocol is designed to evaluate the safety and efficacy of photodepletion (PD) as an improved selective depletion procedure in the HLA-matched peripheral blood stem cell transplant setting and to determine whether post-transplant immunosuppression with cyclosporine is necessary to prevent severe GVHD after a photodepleted transplant.
The protocol will accrue subjects ages 18-75 who are diagnosed with a hematological malignancy where allogeneic stem cell transplantation from an HLA-matched sibling would be normally indicated. Diagnostic categories will include acute and chronic leukemias, myelodysplastic syndromes, B-cell lymphomas, multiple myeloma, and myeloproliferative syndromes.
Participants have a central intravenous (IV) line placed into a large vein. The tube is used for giving the donated stem cells and antibiotics and other medicines, for transfusions of red blood cells and platelets, and for collecting blood samples. Treatment starts with a conditioning regimen of chemotherapy (fludarabine and cyclophosphamide) and total body irradiation to suppress immunity and prevent rejection of the donated stem cells. The day after chemotherapy ends, the stem cells are given through the central line. This is followed by transfusion of the donor's immune cells, which have been treated to remove cells that could cause severe GVHD. Also to minimize the risk of GVHD, patients are given cyclosporine. Not all participants receive the same amount of this drug; in order to determine how much immunosuppression is needed to protect against severe GVHD, the length of treatment with cyclosporine varies among patients, depending on when they entered the study and how well preceding patients did.
The average hospital stay for stem cell transplantation is 3 to 4 weeks. Patients return for frequent follow-up visits for the first 2 to 4 months after transplantation. The patient's referring physician is asked to send results of any laboratory testing to the NIH researchers at least every 3 months for the first 3 years and annually thereafter. Patient follow-up visits are scheduled at NIH at 1, 2, and 3 years after transplantation. After 3 years, participants are offered the opportunity to enroll in NHLBI's long-term evaluation and follow-up care protocol.
Subjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation, followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been selectively depleted using the photodepletion approach (Kiadis Pharma). Older subjects will receive a lower dose of irradiation to reduce the regimen intensity.
To determine appropriate level of post transplant immunosuppression, we will utilize a three sequential de-escalation stage design involving 17 subjects per cohort (minimum 17, maximum 51 total evaluable subjects in study). Stopping rules for non-relapse mortality in each cohort will determine whether to continue to the next stage; to continue accumulating subjects at the same level; or to stop the protocol.
Cohort 1: Low dose cyclosporine until day 90 then dose tapered to stop within 2 weeks.
Cohort 2: If no severe GVHD is encountered in Cohort 1, the cyclosporine withdrawal will begin on day 45.
Cohort 3: If no severe GVHD is encountered in Cohort 2, cyclosporine will not be used in the post-transplant period.
Primary endpoints will be the incidence of acute grade III/IV GVHD at day 90. Secondary endpoints will be standard transplant outcome variables: toxicity, non relapse mortality and survival.
- Conditions
- CML (Chronic Myelogenous Leukemia), CLL (Chronic Lymphocytic Leukemia), AML (Acute Myelogenous Leukemia), Acute Lymphocytic Leukemia, MDS (Myelodysplastic Syndrome)
- Being tested
- Miltenyi system
- Keywords
- CML (Chronic Myelogenous Leukemia), CLL (Chronic Lymphocytic Leukemia), AML (Acute Myelogenous Leukemia), Leukemia, Chronic Lymphocytic Leukemia, CLL, Chronic Myelogenous Leukemia, CML, Acute Myelogenous Leukemia, AML, Acute B-Lymphoblastic Leukemia, ALL, Myelodysplastic Syndrome, MDS
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, B-Cell, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Anemia, Refractory, with Excess of Blasts, Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Miltenyi systemCombination product
Subjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation, followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been selectively depleted using the photodepletion approach.
| Study group | Role | What they receive |
|---|---|---|
| Miltenyi system transplant recipients | Experimental | Subjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation, followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been selectively depleted using the photodepletion approach. Older subjects will receive a lower dose of irradiation to reduce the regimen intensity. Determine appropriate level of post transplant immunosuppression Receives: Combination Product: Miltenyi system |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Determine if Selective T Cell Depletion Using the Photodepletion Procedure Can Substantially Reduce the Rate of Severe Acute GVHD (Grade III/IV) After Matched Sibling Transplantation Followed by Low-dose or no Immunosuppression.
Patients will receive a selectively photodepleted lymphocyte product which will be delivered together with the T cell depleted stem cell product on the day of transplantation. Subjects will receive a conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34-selection and a lymphocyte product that has been selectively depleted using the photodepletion approach. Older subjects will receive a lower dose of irradiation to reduce the regimen intensity. To determine appropriate level of post transplant immunosuppression, a three sequential de-escalation stage design for timing of cyclosporine will be utilized. To determine if selective T cell depletion using the photodepletion procedure can substantially reduce the number of severe acute GVHD (grade III/IV) after transplantation followed by low-dose or no immunosuppression.
Measured: Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2007 (estimated)
- Study startApr 2007
- Primary completionNov 2012
- Study completionNov 2012
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 CML (Chronic Myelogenous Leukemia)Studies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Evaluation of selective depletion of alloreactive T cells to prevent graft vs host disease
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Minocher M Battiwalla, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00467961
- Sponsor's protocol ID
- 070136
- Other IDs
- 07-H-0136
- Status last verified
- Dec 2014
- First submitted
- 28 Apr 2007
- Last updated
- 13 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Appelbaum FR. Haematopoietic cell transplantation as immunotherapy. Nature. 2001 May 17;411(6835):385-9. doi: 10.1038/35077251.
PubMed 11357147Amrolia PJ, Muccioli-Casadei G, Yvon E, Huls H, Sili U, Wieder ED, Bollard C, Michalek J, Ghetie V, Heslop HE, Molldrem JJ, Rooney CM, Schlinder J, Vitetta E, Brenner MK. Selective depletion of donor alloreactive T cells without loss of antiviral or antileukemic responses. Blood. 2003 Sep 15;102(6):2292-9. doi: 10.1182/blood-2002-11-3516. Epub 2003 May 22.
PubMed 12763937Andre-Schmutz I, Le Deist F, Hacein-Bey-Abina S, Vitetta E, Schindler J, Chedeville G, Vilmer E, Fischer A, Cavazzana-Calvo M. Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation: a phase 1/2 study. Lancet. 2002 Jul 13;360(9327):130-7. doi: 10.1016/S0140-6736(02)09413-8.
PubMed 12126823Mielke S, McIver ZA, Shenoy A, Fellowes V, Khuu H, Stroncek DF, Leitman SF, Childs R, Battiwalla M, Koklanaris E, Haggerty J, Savani BN, Rezvani K, Barrett AJ. Selectively T cell-depleted allografts from HLA-matched sibling donors followed by low-dose posttransplantation immunosuppression to improve transplantation outcome in patients with hematologic malignancies. Biol Blood Marrow Transplant. 2011 Dec;17(12):1855-61. doi: 10.1016/j.bbmt.2011.05.019. Epub 2011 May 31.
PubMed 21684344McIver ZA, Yin F, Hughes T, Battiwalla M, Ito S, Koklanaris E, Haggerty J, Hensel NF, Barrett AJ. Second hematopoietic SCT for leukemia relapsing after myeloablative T cell-depleted transplants does not prolong survival. Bone Marrow Transplant. 2013 Sep;48(9):1192-7. doi: 10.1038/bmt.2013.39. Epub 2013 Mar 25.
PubMed 23524640Melenhorst JJ, Tian X, Xu D, Sandler NG, Scheinberg P, Biancotto A, Scheinberg P, McCoy JP Jr, Hensel NF, McIver Z, Douek DC, Barrett AJ. Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation. Haematologica. 2012 Jun;97(6):867-73. doi: 10.3324/haematol.2011.053363. Epub 2011 Dec 1.
PubMed 22133778
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Selective Depletion of Alloreacting T Cells Using a Photodepletion Technique to Prevent GVHD After HLA-Matched Peripheral Blood Stem Cell Transplantation for Subjects With Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00467961
- Acronym / sponsor ID
- 070136
- Conditions
- CML (Chronic Myelogenous Leukemia), CLL (Chronic Lymphocytic Leukemia), AML (Acute Myelogenous Leukemia), Acute Lymphocytic Leukemia, MDS (Myelodysplastic Syndrome)
- Keywords
- CML (Chronic Myelogenous Leukemia), CLL (Chronic Lymphocytic Leukemia), AML (Acute Myelogenous Leukemia), Leukemia, Chronic Lymphocytic Leukemia, CLL, Chronic Myelogenous Leukemia, CML
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Apr 2007
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 1 May 2007 (estimated)
- Results
- Posted 6 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will try to improve the safety and effectiveness of stem cell transplant procedures in patients with cancers of the blood. It will use a special machine to separate immune cells (T cells) from the blood of both the donor and the patient and will use photodepletion, a laboratory procedure that selectively kills cancer cells exposed to light. These special procedures may reduce the risk of graft-versus-host-disease (GVHD), a serious complication of stem cell transplants in which the donor's immune cells destroy the patient's healthy tissues, and at the same time may permit a greater graft-versus-leukemia effect, in which the donated cells fight any residual tumor cells that might remain in the body.
Patients between 18 and 75 years of age with a life-threatening disease of the bone marrow (acute or chronic leukemia, myelodysplastic syndrome, or myeloproliferative syndrome) may be eligible for this study. Candidates must have a family member who is a suitable tissue match.
Detailed description
Peripheral blood stem cell transplant research carried out by the NHLBI BMT Unit focus on approaches in transplant techniques designed to decrease graft versus host disease (GVHD), increase the graft-versus-leukemia (GVL) effect, and/or reduce the risk for post-transplant graft rejection or disease relapse.
Ex vivo selective depletion of alloreacting T cells, hereafter referred as selective depletion (SD), represents a translational strategy aiming to reduce severe GVHD whilst preserving GVL. We found that selectively depleted transplants are safe to administer and associated with less severe acute GVHD. This protocol is designed to evaluate the safety and efficacy of photodepletion (PD) as an improved selective depletion procedure in the HLA-matched peripheral blood stem cell transplant setting and to determine whether post-transplant immunosuppression with cyclosporine is necessary to prevent severe GVHD after a photodepleted transplant.
The protocol will accrue subjects ages 18-75 who are diagnosed with a hematological malignancy where allogeneic stem cell transplantation from an HLA-matched sibling would be normally indicated. Diagnostic categories will include acute and chronic leukemias, myelodysplastic syndromes, B-cell lymphomas, multiple myeloma, and myeloproliferative syndromes.
Participants have a central intravenous (IV) line placed into a large vein. The tube is used for giving the donated stem cells and antibiotics and other medicines, for transfusions of red blood cells and platelets, and for collecting blood samples. Treatment starts with a conditioning regimen of chemotherapy (fludarabine and cyclophosphamide) and total body irradiation to suppress immunity and prevent rejection of the donated stem cells. The day after chemotherapy ends, the stem cells are given through the central line. This is followed by transfusion of the donor's immune cells, which have been treated to remove cells that could cause severe GVHD. Also to minimize the risk of GVHD, patients are given cyclosporine. Not all participants receive the same amount of this drug; in order to determine how much immunosuppression is needed to protect against severe GVHD, the length of treatment with cyclosporine varies among patients, depending on when they entered the study and how well preceding patients did.
The average hospital stay for stem cell transplantation is 3 to 4 weeks. Patients return for frequent follow-up visits for the first 2 to 4 months after transplantation. The patient's referring physician is asked to send results of any laboratory testing to the NIH researchers at least every 3 months for the first 3 years and annually thereafter. Patient follow-up visits are scheduled at NIH at 1, 2, and 3 years after transplantation. After 3 years, participants are offered the opportunity to enroll in NHLBI's long-term evaluation and follow-up care protocol.
Subjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation, followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been selectively depleted using the photodepletion approach (Kiadis Pharma). Older subjects will receive a lower dose of irradiation to reduce the regimen intensity.
To determine appropriate level of post transplant immunosuppression, we will utilize a three sequential de-escalation stage design involving 17 subjects per cohort (minimum 17, maximum 51 total evaluable subjects in study). Stopping rules for non-relapse mortality in each cohort will determine whether to continue to the next stage; to continue accumulating subjects at the same level; or to stop the protocol.
Cohort 1: Low dose cyclosporine until day 90 then dose tapered to stop within 2 weeks.
Cohort 2: If no severe GVHD is encountered in Cohort 1, the cyclosporine withdrawal will begin on day 45.
Cohort 3: If no severe GVHD is encountered in Cohort 2, cyclosporine will not be used in the post-transplant period.
Primary endpoints will be the incidence of acute grade III/IV GVHD at day 90. Secondary endpoints will be standard transplant outcome variables: toxicity, non relapse mortality and survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Evaluation of selective depletion of alloreactive T cells to prevent graft vs host disease
| Arm | Type | Receives |
|---|---|---|
| Miltenyi system transplant recipients | Experimental | Combination Product: Miltenyi systemSubjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation, followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been selectively depleted using the photodepletion approach. Older subjects will receive a lower dose of irradiation to reduce the regimen intensity. Determine appropriate level of post transplant immunosuppression |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Diagnosed with one of the following hematological conditions:
- Chronic myelogenous leukemia (CML): chronic phase who have failed treatment with imatinib, have intolerance to imatinib, or who did not receive imatinib at therapeutic doses within the first 12 months from diagnosis; accelerated phase or blast transformation.
- Acute B-lymphoblastic leukemia (B-ALL): any of these categories: B-ALL in first remission with high-risk features (presenting leukocyte count greater than 100,000/cu mm, Karyotypes t9; 22, t4, t19, t11, biphenotypic leukemia), all second or subsequent remissions, primary induction failure, partially responding or untreated relapse.
- Acute myelogenous leukemia (AML): AML in first remission - except AML with good risk karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), AML t (8; 21). All AML in second or subsequent remission, primary induction failure and resistant relapse.
- Myelodysplastic syndromes (MDS): any of these categories - refractory anemia with transfusion dependence, refractory anemia with excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia, atypical MDS/myeloproliferative syndromes.
Key exclusion criteria (19 listed)
- Malignant cells expressing a T cell phenotype (in particular T-ALL and T cell NHL).
- DLCO less than 65 percent predicted.
- Left ventricular ejection fraction less than 40 percent (evaluated by ECHO) or less than 30 percent (evaluated by MUGA).
- AST/SGOT greater than 10 times ULN (CTCAE grade IV v3.0).
- Bilirubin greater than 5 times ULN (CTCAE grade IV v3.0).
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 |
|---|---|---|
| Miltenyi systemSubjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation, followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been selectively depleted using the photodepletion approach. | Combination product | Miltenyi system transplant recipients |
Primary outcome
To Determine if Selective T Cell Depletion Using the Photodepletion Procedure Can Substantially Reduce the Rate of Severe Acute GVHD (Grade III/IV) After Matched Sibling Transplantation Followed by Low-dose or no Immunosuppression.
Time frame: Day 90
Patients will receive a selectively photodepleted lymphocyte product which will be delivered together with the T cell depleted stem cell product on the day of transplantation. Subjects will receive a conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34-selection and a lymphocyte product that has been selectively depleted using the photodepletion approach. Older subjects will receive a lower dose of irradiation to reduce the regimen intensity. To determine appropriate level of post transplant immunosuppression, a three sequential de-escalation stage design for timing of cyclosporine will be utilized. To determine if selective T cell depletion using the photodepletion procedure can substantially reduce the number of severe acute GVHD (grade III/IV) after transplantation followed by low-dose or no immunosuppression.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11357147Appelbaum FR. Haematopoietic cell transplantation as immunotherapy. Nature. 2001 May 17;411(6835):385-9. doi: 10.1038/35077251.
- Background: PubMed 12763937Amrolia PJ, Muccioli-Casadei G, Yvon E, Huls H, Sili U, Wieder ED, Bollard C, Michalek J, Ghetie V, Heslop HE, Molldrem JJ, Rooney CM, Schlinder J, Vitetta E, Brenner MK. Selective depletion of donor alloreactive T cells without loss of antiviral or antileukemic responses. Blood. 2003 Sep 15;102(6):2292-9. doi: 10.1182/blood-2002-11-3516. Epub 2003 May 22.
- Background: PubMed 12126823Andre-Schmutz I, Le Deist F, Hacein-Bey-Abina S, Vitetta E, Schindler J, Chedeville G, Vilmer E, Fischer A, Cavazzana-Calvo M. Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation: a phase 1/2 study. Lancet. 2002 Jul 13;360(9327):130-7. doi: 10.1016/S0140-6736(02)09413-8.
- Results publication: PubMed 21684344Mielke S, McIver ZA, Shenoy A, Fellowes V, Khuu H, Stroncek DF, Leitman SF, Childs R, Battiwalla M, Koklanaris E, Haggerty J, Savani BN, Rezvani K, Barrett AJ. Selectively T cell-depleted allografts from HLA-matched sibling donors followed by low-dose posttransplantation immunosuppression to improve transplantation outcome in patients with hematologic malignancies. Biol Blood Marrow Transplant. 2011 Dec;17(12):1855-61. doi: 10.1016/j.bbmt.2011.05.019. Epub 2011 May 31.
- Derived from this study: PubMed 23524640McIver ZA, Yin F, Hughes T, Battiwalla M, Ito S, Koklanaris E, Haggerty J, Hensel NF, Barrett AJ. Second hematopoietic SCT for leukemia relapsing after myeloablative T cell-depleted transplants does not prolong survival. Bone Marrow Transplant. 2013 Sep;48(9):1192-7. doi: 10.1038/bmt.2013.39. Epub 2013 Mar 25.
- Derived from this study: PubMed 22133778Melenhorst JJ, Tian X, Xu D, Sandler NG, Scheinberg P, Biancotto A, Scheinberg P, McCoy JP Jr, Hensel NF, McIver Z, Douek DC, Barrett AJ. Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation. Haematologica. 2012 Jun;97(6):867-73. doi: 10.3324/haematol.2011.053363. Epub 2011 Dec 1.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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High-risk Myeloid Malignancy, Allogenic Stem Cell Transplantation
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.
Minocher M Battiwalla, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Miltenyi system in people with CML (Chronic Myelogenous Leukemia) and CLL (Chronic Lymphocytic Leukemia), run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
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 18 inclusion and 19 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 13 Jul 2018. 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 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?
Yes. Results are posted in the registry (first posted 6 Jan 2015). 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?
To Determine if Selective T Cell Depletion Using the Photodepletion Procedure Can Substantially Reduce the Rate of Severe Acute GVHD (Grade III/IV) After Matched Sibling Transplantation Followed by Low-dose or no Immunosuppression. (time frame: Day 90). 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 NCT00467961, 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 13 Jul 2018.