NCT02446964

Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Leukemia

Phase I Study of Escalating Doses of Total Marrow and Lymphoid Irradiation (TMLI) During Conditioning for HLA-Haploidentical Hematopoietic Cell Transplantation With Post-Transplant Cyclophosphamide in Patients With Myelodysplasia or Acute Leukemia

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 12 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of total bone marrow and lymphoid irradiation when given together with chemotherapy before donor stem cell transplant in treating patients with myelodysplastic syndrome or acute leukemia. Total marrow and lymphoid irradiation is a type of radiation therapy that targets bone marrow and blood, where the cancer is, instead of applying radiation to the whole body. Stem cell transplants use high doses of chemotherapy and radiation therapy, such as total marrow and lymphoid irradiation, to kill cancer cells, but these treatments kill normal cells as well. After chemotherapy, healthy cells from a donor are given to the patient to help the patient grow new blood cells.

Detailed description

PRIMARY OBJECTIVES: I. To establish safety and determine the maximum tolerated dose of total marrow and lymphoid irradiation when given in combination with fludarabine (fludarabine phosphate) and pre-post-transplant cyclophosphamide, as conditioning for haploidentical hematopoietic cell transplantation (HCT) in patients with high-risk acute lymphocytic or myelogenous leukemia or intermediate/high-risk myelodysplastic syndrome. II. To evaluate the safety of the regimen at each dose level by assessing adverse events: type, frequency, severity, attribution, time course, duration. III. To evaluate the safety of the regimen at each dose level by assessing complications: including acute/chronic graft-versus-host disease (GvHD), infection and delayed engraftment. SECONDARY OBJECTIVES: I. To estimate overall survival (OS), progression-free survival (PFS), cumulative incidence (CI) of relapse/progression, and non-relapse mortality (NRM) at +100 Days, 1 year and 2 years. II. To characterize minimal residual disease from bone marrow aspirates on Days +30, +100, +180 post-transplant and describe in relation to total marrow and lymphoid irradiation (TMLI) dose level and patient disease status. III. To describe the kinetics of immune cell recovery in the first year post-transplantation. OUTLINE: This is a dose-escalation study of TMLI. CONDITIONING: Patients undergo TMLI twice daily (BID) on days -7 to -4 or -3 (depending on the dose level). Patients also receive fludarabine phosphate intravenously (IV) on days -7 to -3 and cyclophosphamide IV on days -7, -6, 3, and 4. TRANSPLANT: Patients undergo bone marrow or peripheral blood stem cell transplant on day 0. GHVD PROPHYLAXIS: Patients receive tacrolimus\* IV once daily (QD) or orally (PO) BID on days 5-180. Patients also receive mycophenolate mofetil PO thrice daily (TID) or IV on days 5-35. Treatment with tacrolimus and mycophenolate mofetil may continue in the presence of active GVHD. \*NOTE: Patients intolerant of tacrolimus may receive cyclosporine. After completion of study treatment, patients are followed up twice weekly for 100 days, twice monthly until 6 months, monthly until the patient is off immunosuppressive therapy without evidence of GVHD, and then at least yearly for a total of 5 years.

Conditions

• Adult Acute Lymphoblastic Leukemia in Complete Remission
• Acute Myeloid Leukemia in Remission
• Previously Treated Myelodysplastic Syndrome
• Recurrent Adult Acute Lymphoblastic Leukemia
• Recurrent Adult Acute Myeloid Leukemia
• Recurrent Childhood Acute Lymphoblastic Leukemia
• Recurrent Childhood Acute Myeloid Leukemia
• Childhood Acute Lymphoblastic Leukemia in Complete Remission

Interventions

Type	Name	Description
PROCEDURE	Bone Marrow Transplantation	Undergo bone marrow transplant
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine Phosphate	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Mycophenolate Mofetil	Given PO or IV
PROCEDURE	Peripheral Blood Stem Cell Transplantation	Undergo peripheral blood stem cell transplant
DRUG	Tacrolimus	Given IV and PO
RADIATION	Total Marrow Irradiation	Undergo TMLI

Timeline

• Start date: 2015-06-25
• Primary completion: 2025-05-20
• Completion: 2025-05-20
• First posted: 2015-05-18
• Last updated: 2025-06-22

Locations

1 site across 1 country: United States