Graft Versus Host Disease-Reduction Strategies for Donor Blood Stem Cell Transplant Patients With Acute Leukemia or Myelodysplastic Syndrome (MDS)

Conditions

• Acute Leukemia
• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Myelodysplastic Syndrome
• Myeloproliferative Neoplasm

Eligibility Criteria

Sex

ALL

Age

1 Year - 60 Years

Healthy Volunteers

Not accepted

Interventions

• Total-Body Irradiation — RADIATION
  Undergo TBI
• Thiotepa — DRUG
  Given IV
• Fludarabine — DRUG
  Given IV
• Tacrolimus — DRUG
  Given IV
• Allogeneic CD34+-enriched and CD45RA-depleted PBSCs — BIOLOGICAL
  Given IV
• Methotrexate — DRUG
  Given IV
• Cyclophosphamide — DRUG
  Given IV
• Peripheral Blood Stem Cell — BIOLOGICAL
  Given IV
• Cyclosporine — DRUG
  Given IV
• Sirolimus — DRUG
  Given IV
• Busulfan — DRUG
  Given IV
• Bone Marrow Aspiration and Biopsy — PROCEDURE
  Undergo bone marrow aspiration/biopsy
• Echocardiography — PROCEDURE
  Undergo ECHO
• Multigated Acquisition Scan — PROCEDURE
  Undergo MUGA
• Biospecimen Collection — PROCEDURE
  Undergo blood sample collection

Study Details

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.

Key Dates

Start date

Nov 19, 2019

Status verified

Mar 2026

Primary completion

Dec 31, 2027

Completion

Dec 31, 2029

Study Design

Enrollment

120 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Arm A1 (TBI, 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 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.
• Experimental: Arm A2 (busulfan, TnD)
  Patients 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.
• Experimental: Arm C1 (TBI, 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 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.
• Experimental: Arm C2 (busulfan, PTCy, tacrolimus)
  Patients 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.
• Experimental: Arm D1 (TBI, tacrolimus, methotrexate) [DISCONTINUED NOVEMBER 2021]
  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). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.
• Experimental: Arm D2 (busulfan, tacrolimus, methotrexate) [DISCONTINUED NOVEMBER 2021]
  Patients 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.

Primary Outcome Measure

Graft versus host disease (GVHD)-free relapse-free survival (RFS) [ Time Frame: At 2 years ]

Central Contacts

• Marie Bleakley
  206-667-6572
  [email protected]

Locations (3)

Find similar trials in Tampa, FL

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