Spots Global Cancer Trial Database for Clofarabine and Low-Dose Total-Body Irradiation in Treating Patients With Acute Myeloid Leukemia Undergoing Donor Peripheral Blood Stem Cell Transplant

Study Description

Brief Summary: This phase II trial studies the side effects and how well clofarabine works when given together with low-dose total-body irradiation (TBI) in treating patients with acute myeloid leukemia (AML) undergoing donor peripheral blood stem cell transplant (PBSCT). Giving chemotherapy and TBI before a donor PBSCT helps stop the growth of 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.

Detailed Description: PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose of clofarabine in combination with 2, 3, or 4 Gy TBI in preparation for hematopoietic cell transplantation (HCT) from human leukocyte antigen (HLA)-identical related and HLA-matched unrelated donors in patients with AML. (Part 1) II. To determine the efficacy of the maximum tolerated dose of clofarabine combined with 2, 3, or 4 Gy TBI in reducing the 6 month relapse rate in patients with AML compared to our historical experience with fludarabine and 2 Gy TBI. A satisfactory improvement will be considered 6 month relapse rate declines from 35% to 20% among high-risk (objective for low risk group terminated August 2014). (Part 2) SECONDARY OBJECTIVES: I. Leukemia-free and overall survivals. II. Non-relapse mortality (NRM) of \< 5% at 100 days. III. Engraftment rate of \>= 95%. IV. Prognostic significance of cytogenetics and genetic markers not detected by traditional karyotype analysis, with special respect to tyrosine kinase receptor mutations (such as fms-like tyrosine kinase 3 \[FLT3\]), retrovirus-associated deoxyribonucleic acid (DNA) sequences (RAS)- and nucleophosmin gene mutations along with CCAAT/enhancer binding protein, alpha (C/EBP) mutations. V. Rigorous monitoring for minimal residual/recurring disease by standard morphologic, flow cytometric, and molecular techniques in order to facilitate early intervention. VI. To evaluate the pharmacokinetics of clofarabine (pharmacokinetic samples discontinued January 2017). OUTLINE: This is a dose-escalation study of clofarabine. CONDITIONING REGIMEN: Patients receive clofarabine intravenously (IV) over 2 hours on days -6 to -2. Patients also undergo TBI on day 0. IMMUNOSUPPRESSION: Patients with related donors receive cyclosporine orally (PO) every 12 hours on days -3 to 56 with taper to day 180 and mycophenolate mofetil PO every 12 hours on days 0 to 28. Patients with unrelated donors receive cyclosporine PO every 12 hours on days -3 to 100 with taper to day 180 and mycophenolate mofetil PO every 8 hours on days 0 to 40 with taper to day 96. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. After completion of study treatment, patients are followed up at 4 months and then every year thereafter.

Keywords

Eligibility

Minimum Age: 2 Years

Eligible Ages: CHILD, ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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