NCT03602898

Comparing ATG or Post-Transplant Cyclophosphamide to Calcineurin Inhibitor-Methotrexate as GVHD Prophylaxis After Myeloablative Unrelated Donor Peripheral Blood Stem Cell Transplantation

A Randomized Phase II Study to Compare ATG or Post-Transplant Cyclophosphamide to Calcineurin Inhibitor-Methotrexate as GVHD Prophylaxis After Myeloablative Unrelated Donor Peripheral Blood Stem Cell Transplantation

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 65 Years
• Healthy volunteers: Accepted

Summary

This phase II trial studies how well 3 different drug combinations prevent graft versus host disease (GVHD) after donor stem cell transplant. Calcineurin inhibitors, such as cyclosporine and tacrolimus, may stop the activity of donor cells that can cause GVHD. Chemotherapy drugs, such as cyclophosphamide and methotrexate, may also stop the donor cells that can lead to GVHD while not affecting the cancer-fighting donor cells. Immunosuppressive therapy, such as anti-thymocyte globulin (ATG), is used to decrease the body's immune response and reduces the risk of GVHD. It is not yet known which combination of drugs: 1) ATG, methotrexate, and calcineurin inhibitor 2) cyclophosphamide and calcineurin inhibitor, or 3) methotrexate and calcineurin inhibitor may work best to prevent graft versus host disease and result in best overall outcome after donor stem cell transplant.

Detailed description

OUTLINE: CONDITIONING REGIMENS: Participants receive 1 of 3 regimens and are randomized to 1 of 3 arms for GVHD prophylaxis. REGIMEN A: Participants undergo total body irradiation (TBI) twice daily (BID) on days -6 to -4 (-7 to -4 for those \< 18 years), then receive cyclophosphamide IV over 1-2 hours on days -3 and -2. Participants randomized to Arm 2 only receive TBI on days -3 to -1 (-4 to -1 for those \< 18 years). REGIMEN B: Participants receive fludarabine phosphate IV and busulfan IV every 6 hours on days -5 to -2. REGIMEN C: Participants receive busulfan orally (PO) or IV every 6 hours on days -7 to -4 and cyclophosphamide IV over 1-2 hours on days -3 and -2. Myelofibrosis or other myeloproliferative neoplasms: Participants \>= 18 years receive cyclophosphamide IV over 1-2 hours on days -7 and -6 and busulfan IV on days -5 to -2. Participants \< 17 years receive busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2. All participants undergo peripheral blood stem cell transplantation on day 0. ARM 1: Participants receive anti-thymocyte globulin IV over 4-6 hours on days -3 to -1. Beginning day -1, participants also receive tacrolimus IV or cyclosporine IV twice daily (BID) tapered at day 50, and methotrexate IV on days 1, 3, 6 and 11 in the absence of disease progression or unacceptable toxicity. ARM 2: Participants receive cyclophosphamide IV over 1-2 hours on days 3 and 4. Beginning day 5, participants also receive tacrolimus IV or cyclosporine IV BID tapered at day 50 in the absence of disease progression or unacceptable toxicity. ARM 3: Beginning day -1, participants receive tacrolimus IV or cyclosporine IV BID tapered at day 50, and methotrexate IV on days 1, 3, 6 and 11 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up at 6 months, then annually up to 5 years.

Conditions

• Acute Lymphoblastic Leukemia in Remission
• Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
• Chronic Myelomonocytic Leukemia
• Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Hematopoietic and Lymphoid System Neoplasm
• Myelodysplastic Syndrome
• Myelofibrosis
• Myeloproliferative Neoplasm
• Recurrent Acute Myeloid Leukemia
• Recurrent Hodgkin Lymphoma
• Recurrent Non-Hodgkin Lymphoma
• Refractory Acute Myeloid Leukemia
• Therapy-Related Acute Myeloid Leukemia

Interventions

Type	Name	Description
BIOLOGICAL	Anti-Thymocyte Globulin	Given IV
DRUG	Busulfan	Given IV or PO
DRUG	Cyclophosphamide	Given IV
DRUG	Cyclosporine	Given IV or PO
DRUG	Fludarabine Phosphate	Given IV
DRUG	Methotrexate	Given IV
PROCEDURE	Peripheral Blood Stem Cell Transplantation	Undergo peripheral blood stem cell transplantation
OTHER	Quality-of-Life Assessment	Ancillary studies
OTHER	Questionnaire Administration	Ancillary studies
DRUG	Tacrolimus	Given IV or PO
RADIATION	Total-Body Irradiation	Undergo TBI

Timeline

• Start date: 2021-06-01
• Primary completion: 2023-09-17
• Completion: 2023-09-17
• First posted: 2018-07-27
• Last updated: 2021-06-30

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study