NCT04002115

Clofarabine Pre-conditioning Followed by Stem Cell Transplant for Non-remission AML

Clofarabine Pre-conditioning Followed by Hematopoietic Stem Cell Transplant With Post-Transplant Cyclophosphamide for Non-remission Acute Myeloid Leukemia

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Milton S. Hershey Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Not accepted

Summary

The Investigators would like to study the incidence of complete remission (CR) at day +30 after Clofarabine followed by haploidentical transplant. The conditioning regimen used is Fludarabine, Busulfan (2 doses) or cyclophosphamide (2 doses) and Total Body Irradiation (TBI) with post transplant cyclophosphamide for patients with Acute Myeloid Leukemia (AML) who are not in remission prior to considering allogeneic transplant with haploidentical donors.

Detailed description

Approximately 30-40% of patients with acute myeloid leukemia (AML) experience induction failures. In these patients who do not achieve remission with two cycles of standard induction therapies, the probability of achieving remission with subsequent inductions is limited. Hematopoietic stem cell transplantation (HSCT) is the only curative option for these patients, but high relapse rate and transplant-related mortality often preclude them to proceed to transplant. Thus, AML not in remission at time of HSCT remains a huge unmet need in current HSCT practice, particularly if the patient does not have a Human Leukocyte Antigen (HLA)-matched donor identified by the time of two induction failures. Salvage chemotherapy with clofarabine appears to be another promising option in relapsed and refractory AML. Clofarabine is a second-generation purine nucleoside analog with substantial single-agent activity in adult patients with AML. It is an effective immunosuppressive agent and several trials have shown the feasibility of conditioning with clofarabine-based regimen. In the past, a conditioning regimen of clofarabine with busulfan (4 doses) has been successfully used prior to allogeneic stem cell transplantation for non-remission AML with day +30 complete remission rates were 90-100%. However, these patients were transplanted with HLA matched donors. This study will examine those patients undergoing transplantation from haploidentical related donor or matched and mismatched unrelated donors. Achieving a long-term remission is clearly the goal of AML treatment. The investigators would like to propose a protocol for non-remission AML and expand the patient population to older than 55 years of age as well as those who relapsed after initial allogeneic transplant to improve enrolling patients in the near future. The investigators have many patients achieving remission but for those without remission, clofarabine preconditioning may be a reliable protocol to bring these patients into the early complete remission.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Clofarabine	Clofarabine to be administered pre-stem cell transplant infusion ("Day 0") once a day for 5 days total.
DRUG	Fludarabine	Fludarabine will be administered once a day for 4 days as part of the transplant conditioning regimen.
DRUG	Busulfan	Busulfan will be administered once a day for 2 days as part of the transplant conditioning regimen.
PROCEDURE	Total Body Irradiation (TBI)	TBI will be administered at a dose of 200cGys on Day -1 prior to transplant
DRUG	Cyclophosphamide	Cyclophosphamide will be given once a day for 2 days after the transplant infusion.
DRUG	Granulocyte Colony-Stimulating Factor	G-CSF will be administered to subjects starting on Day +5 and will continue as clinically indicated
DRUG	Tacrolimus	Tacrolimus will be administered to subjects starting on Day +5 and will continue as clinically indicated
DRUG	Cellcept	Mycophenolate Mofetil will be administered to subjects starting on Day +5 and will continue as clinically indicated

Timeline

• Start date: 2020-06-03
• Primary completion: 2022-08-30
• Completion: 2022-11-07
• First posted: 2019-06-28
• Last updated: 2023-09-14
• Results posted: 2023-09-14

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study