Clofarabine Pre-conditioning Followed by Stem Cell Transplant for Non-remission AML
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|ClinicalTrials.gov Identifier: NCT04002115|
Recruitment Status : Recruiting
First Posted : June 28, 2019
Last Update Posted : October 11, 2021
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia||Drug: Clofarabine Drug: Fludarabine Drug: Busulfan Procedure: Total Body Irradiation (TBI) Drug: Cyclophosphamide Drug: Granulocyte Colony-Stimulating Factor Drug: Tacrolimus Drug: Cellcept||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Dose de-escalation: Enrollment will begin at 30 mg/m2 to analyze any grade 4-5 organ toxicities as defined in Section 12.2. If the trial is stopped due to excessive toxicities, then dose de-escalation to 20 mg/m2 will occur for the next cohort of participants. For each participant, the observation period is from start of treatment through post-transplant day +30. Adverse effects will be continuously monitored as patients are enrolled. The trial will be stopped when the toxicity rate exceeds 20% with a posterior probability of 80% and a margin of no more than 5%. This leads to the following stopping rule: the trial will be stopped if 2 of the first 3 subjects experience grade 4-5 organ toxicity, or 3 out of 6, 4 out 9, 5 out of 12, 6 out of 16, or 7 out 19.|
|Masking:||None (Open Label)|
|Official Title:||Clofarabine Pre-conditioning Followed by Hematopoietic Stem Cell Transplant With Post-Transplant Cyclophosphamide for Non-remission Acute Myeloid Leukemia|
|Actual Study Start Date :||June 3, 2020|
|Estimated Primary Completion Date :||June 3, 2022|
|Estimated Study Completion Date :||June 3, 2026|
Experimental: Clofarabine 30 mg/m^2
Day -14 through Day -10 Clofarabine 30 mg/m^2, Day - 9 Day of rest, Day - 8 Day of rest, Day - 7 Day of rest, Day - 6 Fludarabine 40 mg/m^2 IV and Busulfan 3.2 mg/kg IV (Regimen A, Fludarabine 24 mg/m^2 IV and Cyclophosphamide 14.5 mg/kg IV for Regimen B), Day - 5 Fludarabine 40 mg/m^2 IV and Busulfan 3.2 mg/kg IV (Regimen A, Fludarabine 24 mg/m^2 IV and Cyclophosphamide 14.5 mg/kg IV for Regimen B), Day - 4 Fludarabine 40 mg/m^2 IV(Regimen A, Fludarabine 24 mg/m^2 IV for Regimen B), Day - 3 Fludarabine 40 mg/m^2 IV(Regimen A, Fludarabine 24 mg/m^2 IV for Regimen B), Day - 2 Day of Rest, Day -1 Total Body Irradiation 200 cGys, Day 0 stem cell transplant infusion, Day +1 Day of rest, Day +2 Day of rest, Day +3 Cyclophosphamide 50 mg/kg IV, Day +4 Cyclophosphamide 50 mg/kg IV, Day +5 Start G-CSF, Tacrolimus, and MMF.
Clofarabine to be administered pre-stem cell transplant infusion ("Day 0") once a day for 5 days total.
Other Name: Clolar
Fludarabine will be administered once a day for 4 days as part of the transplant conditioning regimen.
Other Name: Fludara
Busulfan will be administered once a day for 2 days as part of the transplant conditioning regimen.
Other Name: Busulfex
Procedure: Total Body Irradiation (TBI)
TBI will be administered at a dose of 200cGys on Day -1 prior to transplant
Other Name: TBI
Cyclophosphamide will be given once a day for 2 days after the transplant infusion.
Other Name: Cytoxan
Drug: Granulocyte Colony-Stimulating Factor
G-CSF will be administered to subjects starting on Day +5 and will continue as clinically indicated
Other Name: Filgrastim G-CSF
Tacrolimus will be administered to subjects starting on Day +5 and will continue as clinically indicated
Other Name: Prograf
Mycophenolate Mofetil will be administered to subjects starting on Day +5 and will continue as clinically indicated
Other Name: Mycophenolate Mofetil (MMF)
- Incidence of complete remission (CR) [ Time Frame: 30 days ]Determine the incidence of CR at 30 days (Day +30) post stem cell transplant infusion
- Non-relapse related mortality [ Time Frame: 100 days ]Determine the rate of non-relapse related mortality at 100 days post transplant (Day +100)
- Neutrophil engraftment [ Time Frame: 1 year ]Rates of engraftment, defined as the first day of Absolute Neutrophil Count (ANC) greater than 500 for the first of three consecutive days
- Incidence of Acute graft-versus-host disease (GVHD) [ Time Frame: 100 days ]The incidence of any grade (1-4) of acute GvHD as measured from day of transplantation to Day +100 using the Glucksberg criteria.
- Severity of Acute graft-versus-host disease (GVHD) [ Time Frame: 100 days ]The highest grade (1-4) of acute GvHD experienced by participants as measured from day of transplantation to Day +100 using the Glucksberg criteria
- Incidence of Chronic GVHD [ Time Frame: 1 year ]The incidence of any grade (1-4) of acute GvHD as measured from Day +100 to Year 1 post-transplantation using the Glucksberg criteria.
- Severity of Chronic GVHD [ Time Frame: 1 year ]The highest overall grade (1-4) of chronic GvHD experienced by participants as measured from Day +100 to Year 1 post-transplantation using the Glucksberg criteria
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04002115
|Contact: Seema Naik, MDfirstname.lastname@example.org|
|Contact: Clinical Research Nurse - Leukemia||717-531-5471|
|United States, Pennsylvania|
|Penn State Cancer Institute||Recruiting|
|Hershey, Pennsylvania, United States, 17033|
|Contact: Seema Naik, MD 717-531-6585 email@example.com|
|Principal Investigator:||Seema Naik, MD||Penn State Cancer Institute|