NCT01252667

Clofarabine and Low-Dose Total-Body Irradiation in Treating Patients With Acute Myeloid Leukemia Undergoing Donor Peripheral Blood Stem Cell Transplant

A Phase II Study of Optimally Dosed Clofarabine in Combination With Low-Dose TBI to Decrease Relapse Rates After Related or Unrelated Donor Hematopoietic Cell Transplantation in Patients With AML

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 44 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 2 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
PROCEDURE	Allogeneic Hematopoietic Stem Cell Transplantation	Undergo allogeneic hematopoietic PBSCT
DRUG	Clofarabine	Given IV
DRUG	Cyclosporine	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Mycophenolate Mofetil	Given PO
PROCEDURE	Peripheral Blood Stem Cell Transplantation	Undergo allogeneic hematopoietic PBSCT
OTHER	Pharmacological Study	Optional correlative studies
RADIATION	Total-Body Irradiation	Undergo TBI

Timeline

• Start date: 2011-01-25
• Primary completion: 2019-01-25
• Completion: 2019-03-01
• First posted: 2010-12-03
• Last updated: 2020-04-16
• Results posted: 2020-04-16

Locations

4 sites across 1 country: United States