Condition or disease | Intervention/treatment | Phase |
---|---|---|
Acute Biphenotypic Leukemia Acute Leukemia of Ambiguous Lineage Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Acute Undifferentiated Leukemia Blastic Plasmacytoid Dendritic Cell Neoplasm Lymphoblastic Lymphoma Mixed Phenotype Acute Leukemia Acute Leukemia Hematopoietic and Lymphoid Cell Neoplasm | Radiation: Total-Body Irradiation Drug: Thiotepa Drug: Fludarabine Drug: Tacrolimus Biological: Allogeneic CD34+-enriched and CD45RA-depleted PBSCs Drug: Methotrexate Drug: Cyclophosphamide Biological: Peripheral Blood Stem Cell Drug: Cyclosporine Drug: Sirolimus | Phase 2 |
OUTLINE:
Patients are randomized to 1 of 3 arms.
ARM A: Patients undergo total-body irradiation (TBI) twice daily (BID) on days -10 to -7, and receive thiotepa intravenously (IV) over 3 hours on days -6 and -5, fludarabine IV over 30 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).
ARM C: Patients 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 hour 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).
ARM D: Patients 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).
After completion of study treatment, patients are followed up at days 7, 14, 21, 28, 56, 80, 180, and 270 and at 1, 1.5, and 2 years.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 120 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase II Randomized Controlled Trial Comparing GVHD-Reduction Strategies for Allogeneic Peripheral Blood Transplantation (PBSCT) for Patients With Acute Leukemia: Selective Depletion of CD45RA+ Naïve T Cells (TND) vs.Post-Transplantation Cyclophosphamide (PTCy) vs. Tacrolimus and Methotrexate (TacMTX) PBSCT |
Actual Study Start Date : | November 19, 2019 |
Estimated Primary Completion Date : | August 1, 2023 |
Estimated Study Completion Date : | August 1, 2024 |
Arm | Intervention/treatment |
---|---|
Experimental: Arm A (TnD)
Patients undergo TBI BID on days -10 to -7, and receive thiotepa IV over 3 hours on days -6 and -5, fludarabine IV over 30 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).
|
Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
Drug: Thiotepa Given IV
Other Names:
Drug: Fludarabine Given IV
Other Name: Fluradosa
Drug: Tacrolimus Given IV
Other Names:
Biological: Allogeneic CD34+-enriched and CD45RA-depleted PBSCs Given IV
Other Names:
Drug: Methotrexate Given IV
Other Names:
Drug: Cyclosporine Given IV
Other Names:
Drug: Sirolimus Given IV
Other Names:
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Experimental: Arm C (PTCy, tacrolimus)
Patients 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 hour 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).
|
Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
Drug: Tacrolimus Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Biological: Peripheral Blood Stem Cell Given IV
Other Names:
Drug: Cyclosporine Given IV
Other Names:
Drug: Sirolimus Given IV
Other Names:
|
Experimental: Arm D (tacrolimus, methotrexate)
Patients 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).
|
Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
Drug: Tacrolimus Given IV
Other Names:
Drug: Methotrexate Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Biological: Peripheral Blood Stem Cell Given IV
Other Names:
Drug: Cyclosporine Given IV
Other Names:
Drug: Sirolimus Given IV
Other Names:
|
Ages Eligible for Study: | 1 Year and older (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Patients who are considered appropriate candidates for myeloablative, TBI-containing allogeneic hematopoietic stem cell transplantation and have one of the following diagnoses:
DONOR: Matched related donors:
DONOR: Matched unrelated donors:
Exclusion Criteria:
Patient weight:
Patients with organ dysfunction, including:
Contact: Marie Bleakley | 206-667-6572 | mbleakle@fredhutch.org |
United States, Florida | |
Moffitt Cancer Center | Not yet recruiting |
Tampa, Florida, United States, 33612 | |
Contact: Taiga Nishihori 813-745-4673 taiga.nishihori@moffitt.org | |
Principal Investigator: Taiga Nishihori | |
United States, Pennsylvania | |
University of Pittsburgh Cancer Institute (UPCI) | Recruiting |
Pittsburgh, Pennsylvania, United States, 15232 | |
Contact: Alison Sehgal 412-623-2861 sehgalar@upmc.edu | |
Principal Investigator: Alison Sehgal | |
United States, Washington | |
Fred Hutch/University of Washington Cancer Consortium | Recruiting |
Seattle, Washington, United States, 98109 | |
Contact: Marie Bleakley 206-667-6572 mbleakle@fredhutch.org | |
Principal Investigator: Marie Bleakley |
Principal Investigator: | Marie Bleakley | Fred Hutch/University of Washington Cancer Consortium |
Tracking Information | |||||
---|---|---|---|---|---|
First Submitted Date ICMJE | May 29, 2019 | ||||
First Posted Date ICMJE | May 31, 2019 | ||||
Last Update Posted Date | April 29, 2021 | ||||
Actual Study Start Date ICMJE | November 19, 2019 | ||||
Estimated Primary Completion Date | August 1, 2023 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Graft versus host disease (GVHD)-free relapse-free survival (RFS) [ Time Frame: At 2 years ] 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.
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Graft Versus Host Disease-Reduction Strategies for Donor Blood Stem Cell Transplant Patients With Acute Leukemia | ||||
Official Title ICMJE | A Phase II Randomized Controlled Trial Comparing GVHD-Reduction Strategies for Allogeneic Peripheral Blood Transplantation (PBSCT) for Patients With Acute Leukemia: Selective Depletion of CD45RA+ Naïve T Cells (TND) vs.Post-Transplantation Cyclophosphamide (PTCy) vs. Tacrolimus and Methotrexate (TacMTX) PBSCT | ||||
Brief Summary | This phase II trial investigates three strategies and how well they work for the reduction of graft versus host disease in patients with acute leukemia 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. | ||||
Detailed Description |
OUTLINE: Patients are randomized to 1 of 3 arms. ARM A: Patients undergo total-body irradiation (TBI) twice daily (BID) on days -10 to -7, and receive thiotepa intravenously (IV) over 3 hours on days -6 and -5, fludarabine IV over 30 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). ARM C: Patients 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 hour 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). ARM D: Patients 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). After completion of study treatment, patients are followed up at days 7, 14, 21, 28, 56, 80, 180, and 270 and at 1, 1.5, and 2 years. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
120 | ||||
Original Estimated Enrollment ICMJE |
160 | ||||
Estimated Study Completion Date ICMJE | August 1, 2024 | ||||
Estimated Primary Completion Date | August 1, 2023 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 1 Year and older (Child, Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03970096 | ||||
Other Study ID Numbers ICMJE | RG1005364 9749 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ) NCI-2019-03188 ( Registry Identifier: CTRP ) P30CA015704 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Fred Hutchinson Cancer Research Center | ||||
Study Sponsor ICMJE | Fred Hutchinson Cancer Research Center | ||||
Collaborators ICMJE | National Cancer Institute (NCI) | ||||
Investigators ICMJE |
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PRS Account | Fred Hutchinson Cancer Research Center | ||||
Verification Date | April 2021 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |