Graft Versus Host Disease-Reduction Strategies for Donor Blood Stem Cell Transplant Patients With Acute Leukemia or Myelodysplastic Syndrome (MDS)
A Phase II Randomized Controlled Trial Comparing GVHD-Reduction Strategies for Allogeneic Peripheral Blood Transplantation (PBSCT) for Patients With Acute Leukemia or Myelodysplastic Syndrome: Selective Depletion of CD45RA+ Naïve T Cells (TND) vs. Post-Transplantation Cyclophosphamide (PTCy)
5 other identifiers
interventional
120
1 country
3
Brief Summary
This phase II trial investigates two strategies and how well they work for the reduction of graft versus host disease in patients with acute leukemia or MDS in remission. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and 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. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Nov 2019
Longer than P75 for phase_2
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 29, 2019
CompletedFirst Posted
Study publicly available on registry
May 31, 2019
CompletedStudy Start
First participant enrolled
November 19, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2029
March 12, 2026
March 1, 2026
8.1 years
May 29, 2019
March 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Graft versus host disease (GVHD)-free relapse-free survival (RFS)
Will be defined as survival-free of a history of: a) relapse after hematopoietic cell transplantation (HCT), b) grade III-IV acute GVHD after HCT, moderate or severe chronic GVHD meeting National Institutes of Health (NIH) criteria and requiring systemic pharmacologic immunosuppression for treatment of GVHD. RFS distribution will be estimated for each arm by the Kaplan-Meier curve, starting from the time of HCT. A 90% confidence interval (CI) will be constructed at 1 and 2-year post-HCT timepoints.
At 2 years
Secondary Outcomes (5)
Overall survival (OS)
At 2 years
Relapse
At 2 years
Proportion of patients alive and off prednisone (or equivalent systemic corticosteroid) for treatment of GVHD
At 3, 6, 9, 12, 15, 18, 21, 24 months post HCT
Graft rejection or irreversible graft failure (> 14 days duration)
At 2 years
Incidence of chronic GVHD
Up to 2 years
Study Arms (6)
Arm A1 (TBI, TnD)
EXPERIMENTALPatients undergo TBI BID on days -10 to -7, and receive thiotepa IV over 3 hours on days -6 and -5, fludarabine IV over 30 to 60 minutes on days -6 to -2, tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day -1, CD34+ enriched CD45RA-depleted donor T-lymphocytes IV on day 0, and methotrexate IV on days 1, 3, 6, and 11. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.
Arm A2 (busulfan, TnD)
EXPERIMENTALPatients receive fludarabine IV over 30 to 60 minutes on days -6 to -2, busulfan IV over 180 minutes on days -5 to -2, and undergo TBI BID on day -1. Patients also receive tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day -1, CD34+ enriched CD45RA-depleted donor T-lymphocytes IV on day 0, and methotrexate IV on days 1, 3, 6, and 11. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.
Arm C1 (TBI, PTCy, tacrolimus)
EXPERIMENTALPatients undergo TBI BID on days -4 to -2 or -3 to -1, and receive PBSC IV on day 0. Patients also receive cyclophosphamide IV over 1 to 2 hours on days 3 and 4, and tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day 5. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.
Arm C2 (busulfan, PTCy, tacrolimus)
EXPERIMENTALPatients receive fludarabine IV over 30 to 60 minutes on days -5 to -2, busulfan IV over 180 minutes on days -5 to -2, PBSC IV on day 0, cyclophosphamide IV over 1 to 2 hours on days 3 and 4, and tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day 5. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.
Arm D1 (TBI, tacrolimus, methotrexate) [DISCONTINUED NOVEMBER 2021]
EXPERIMENTALPatients undergo TBI BID on days -6 to -4, and receive cyclophosphamide IV over 1 hour on days -3 to -2, tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day -1, PBSC IV on day 0, and methotrexate IV on days 1, 3, 6, and 11. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.
Arm D2 (busulfan, tacrolimus, methotrexate) [DISCONTINUED NOVEMBER 2021]
EXPERIMENTALPatients receive busulfan IV over 180 minutes on days -8 to -5, cyclophosphamide IV over 1 hour on days -3 to -2, tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day -1, PBSC IV on day 0, and methotrexate IV on days 1, 3, 6, and 11. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.
Interventions
Given IV
Given IV
Given IV
Given IV
Given IV
Given IV
Given IV
Given IV
Given IV
Undergo bone marrow aspiration/biopsy
Undergo ECHO
Undergo MUGA
Undergo blood sample collection
Undergo TBI
Given IV
Eligibility Criteria
You may qualify if:
- Patients who are considered appropriate candidates for myeloablative, TBI-containing allogeneic hematopoietic stem cell transplantation and have one of the following diagnoses:
- Acute lymphocytic leukemia (ALL) in first or subsequent morphological remission (\< 5% marrow blasts by morphology).
- Acute myeloid leukemia (AML) in first or subsequent morphological remission (\< 5% marrow blasts by morphology).
- Other acute leukemia or related neoplasm (including but not limited to 'mixed phenotype' 'biphenotypic', 'acute undifferentiated' or 'ambiguous lineage' acute leukemia, blastic plasmacytoid dendritic cell neoplasm, lymphoblastic lymphoma, Burkitt leukemia/lymphoma, mast cell leukemia, chronic myeloid leukemia \[CML\] with blast crisis or other chronic myeloproliferative neoplasm) in first or subsequent morphological remission (\<5% marrow blasts by morphology).
- Myelodysplastic syndrome (MDS) with a history of excess blasts (≥ approximately 5% in marrow blasts by morphology) and a history of receiving cytoreductive therapy (including but not limited to BCL-2 inhibitors or cytotoxic chemotherapy) within the past 3 months.
- Patient age 1-60 years old (inclusive) at the time of informed consent
- Patients aged 1-50 years old (inclusive) are eligible for TBI-based conditioning regimens.
- Patients aged 1-60 years old (inclusive) are eligible for busulfan-based conditioning regimens (with or without TBI 4 Gy).
- Patient with an HLA-matched (HLA-A, B, C, DRB1, and DQB1 matched) related or unrelated donor capable of donating PBSC.
- Recipient informed consent/assent and/or legal guardian permission must be obtained.
- DONOR: HLA-matched related and unrelated donors (HLA-A, B, C, DRB1 and DQB1 matched based on high-resolution typing).
- DONOR: \>= 18 years old.
- DONOR: Willing to donate PBSC.
- DONOR: Matched related donors:
- Must give informed consent using the related donor informed consent form.
- +4 more criteria
You may not qualify if:
- Patients with central nervous system (CNS) involvement refractory to intrathecal chemotherapy and/or standard cranial-spinal radiation. A patient may have a history of CNS disease. However, any CNS disease must be cleared by the end of the pre-conditioning evaluation time frame. If CNS disease is identified on cerebrospinal fluid (CSF) evaluation within 30 days of the start of the preparative regimen a repeat CSF evaluation must be performed and show no evidence of disease in order for the patient to be eligible for the protocol.
- Patients on other experimental protocols for prevention of GVHD.
- Patient weight:
- Patients with HLA-matched related donors will be excluded if they weigh \>= 110 kg.
- Patients with HLA-matched unrelated donors will be excluded if they weigh \>= 110 kg and must be discussed with the Fred Hutch protocol principal investigator (PI) if they weigh \>= 90 kg.
- Patients who are positive for human immunodeficiency virus (HIV)-1, HIV-2, human T-cell lymphotropic virus (HTLV)1 or HTLV2.
- Patients with uncontrolled infections for whom myeloablative HCT is considered contraindicated by the consulting infectious disease physician; i.e. patients with active infections require infectious disease consultation and documentation by the infectious disease team that myeloablative HCT is not considered to be contraindicated. Upper respiratory tract infection is not considered to represent an uncontrolled infection in this context.
- Patients with organ dysfunction, including:
- Renal insufficiency (creatinine \> 1.5 mg/dl) at the time of evaluation for the protocol. Patients with a known history of creatinine \> 1.5 mg/dl or a current serum creatinine above the normal range for age must have a current creatinine clearance of \> 60 ml/min/1.73 m\^2 (measured by 24-hr urine specimen or nuclear glomerular filtration rate \[GFR\]).
- Left ventricular ejection fraction \< 45%.
- Carbon monoxide diffusing capability (DLCO) corrected \< 60%. Patients who are unable to perform pulmonary function tests (for example, due to young age and/or developmental status) will be excluded if the oxygen (O2) saturation is \< 92% on room air.
- Liver function abnormality. Patients who have liver function test (LFT)s (specifically, total bilirubin, aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\]) \>= twice the upper limit of normal should be evaluated by a gastrointestinal (GI) physician unless there is a clear precipitating factor (such as an azole, MTX, trimethoprim-sulfamethoxazole, or another drug). If the GI physician considers that HCT on the protocol is contraindicated, that patient will be excluded from the protocol. Patients with Gilbert's syndrome require GI physician consultation but may be included on the protocol. Patients with no other known liver function abnormality or with reversible drug-related transaminitis do not necessarily require GI consultation and may be included on the protocol.
- Patients who have received previous myeloablative allogeneic or autologous transplantation.
- Patients with a life expectancy \< 12 months from co-existing disease other than the leukemia or MDS.
- Patients who are pregnant or breast-feeding.
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (3)
Moffitt Cancer Center
Tampa, Florida, 33612, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Marie Bleakley
Fred Hutch/University of Washington Cancer Consortium
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 29, 2019
First Posted
May 31, 2019
Study Start
November 19, 2019
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2029
Last Updated
March 12, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share