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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.

Fludarabine will be administered once a day for 4 days as part of the transplant conditioning regimen.

Busulfan will be administered once a day for 2 days as part of the transplant conditioning regimen.

TBI will be administered at a dose of 200cGys on Day -1 prior to transplant

Total Body Irradiation (TBI)

Cyclophosphamide will be given once a day for 2 days after the transplant infusion.

G-CSF will be administered to subjects starting on Day +5 and will continue as clinically indicated

Granulocyte Colony-Stimulating Factor

Tacrolimus will be administered to subjects starting on Day +5 and will continue as clinically indicated

Mycophenolate Mofetil will be administered to subjects starting on Day +5 and will continue as clinically indicated

Cellcept

Seema Naik, MD

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.

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.

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.

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

At this time there is no plan to share IPD with other researchers outside of Penn State University

The CR rate at 30 days (Day +30) post stem cell transplant infusion

Determine the rate of non-relapse related mortality at 100 days post transplant (Day +100)

Rates of engraftment, defined as the first day of Absolute Neutrophil Count (ANC) greater than 500 for the first of three consecutive days

The rate of any grade (1-4) of acute GvHD as measured from day of transplantation to Day +100 using the Glucksberg criteria.

The highest grade (1-4) of acute GvHD experienced by participants as measured from day of transplantation to Day +100 using the Glucksberg criteria

The rate of any grade (1-4) of Chronic GvHD as measured from Day +100 to Year 1 post-transplantation using the Glucksberg criteria.

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

Milton S. Hershey Medical Center

Associate Professor of the Penn State Cancer Institute

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 24 mg/m\^2 IV and Cyclophosphamide 14.5 mg/kg IV for Regimen B, Day - 5, Fludarabine 24 mg/m\^2 IV and Cyclophosphamide 14.5 mg/kg IV for Regimen B, Day - 4 Fludarabine 24 mg/m\^2 IV for Regimen B, Day - 3 Fludarabine 24 mg/m\^2 IV for Regimen B, Day - 2 Fludarabine 24 mg/m\^2 IV for Regimen, 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 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 24 mg/m\^2 IV and Cyclophosphamide 14.5 mg/kg IV for Regimen B, Day - 5 Fludarabine 24 mg/m\^2 IV and Cyclophosphamide 14.5 mg/kg IV for Regimen B, Day - 4 Fludarabine 24 mg/m\^2 IV for Regimen B, Day - 3 Fludarabine 24 mg/m\^2 IV for Regimen B, Day - 2 Fludarabine 24 mg/m\^2 IV for Regimen B, 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.

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Due to slow accrual, the study was terminated.

Dr. Seema Naik

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 24 mg/m\^2 IV and Cyclophosphamide 14.5 mg/kg IV for Regimen B, Day - 5 Fludarabine 24 mg/m\^2 IV and Cyclophosphamide 14.5 mg/kg IV for Regimen B, Day - 4 Fludarabine 24 mg/m\^2 IV for Regimen B, Day - 3 Fludarabine 24 mg/m\^2 IV for Regimen B, Day - 2 Fludarabine 24 mg/m\^2 IV for Regimen B, 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.

The CR rate at 30 days (Day +30) post stem cell transplant infusion was 2/2.

Complete Remission (CR) Rate at Day 30 Post HSCT

The rate of non-relapse related mortality at 100 days post transplant (Day +100) is 0/2.

Non-relapse Related Mortality

Neutrophil Engraftment

The rate of any grade (1-4) of acute GvHD as measured from day of transplantation to Day +100 was 0/2.

Rate of Acute Graft-versus-host Disease (GVHD)

The highest grade (1-4) of acute GvHD experienced by participants as measured from day of transplantation to Day +100 was 0/2.

Severity of Acute Graft-versus-host Disease (GVHD)

The incidence of any grade (1-4) of Chronic GvHD as measured from Day +100 to Year 1 post-transplantation was 0/2.

Rate of Chronic GVHD

The highest overall grade (1-4) of chronic GvHD experienced by participants as measured from Day +100 to Year 1 post-transplantation was 0/2.

Severity of Chronic GVHD

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 24 mg/m\^2 IV and Cyclophosphamide 14.5 mg/kg IV for Regimen B, Day - 5 Fludarabine 24 mg/m\^2 IV and Cyclophosphamide 14.5 mg/kg IV, Day - 4 Fludarabine 24 mg/m\^2 IV, Day - 3 Fludarabine 24 mg/m\^2 IV, Day - 2 Fludarabine 24 mg/m\^2 IV, 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: Clofarabine to be administered pre-stem cell transplant infusion ("Day 0") once a day for 5 days total.

Fludarabine: Fludarabine will be administered once a day for 5 days as part of the transplant conditioning regimen.

Total Body Irradiation (TBI): TBI will be administered at a dose of 200cGys on Day -1 prior to transplant

Cyclophosphamide: Cyclophosphamide will be given once a day for 2 days after the transplant infusion.

Granulocyte Colony-Stimulating Factor: G-CSF will be administered to subjects starting on Day +5 and will continue as clinically indicated

Tacrolimus: Tacrolimus will be administered to subjects starting on Day +5 and will continue as clinically indicated

Cellcept: Mycophenolate Mofetil will be administered to subjects starting on Day +5 and will continue as clinically indicated

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Clofarabine Pre-conditioning Followed by Stem Cell Transplant for Non-remission AML	NCT04002115	Acute Myeloid L...	Clofarabine Fludarabine Busulfan Total Body Irra... Cyclophosphamid... Granulocyte Col... Tacrolimus Cellcept	18 Years - 55 Years	Milton S. Hershey Medical Center
Clofarabine Pre-conditioning Followed by Stem Cell Transplant for Non-remission AML	NCT04002115	Acute Myeloid L...	Clofarabine Fludarabine Busulfan Total Body Irra... Cyclophosphamid... Granulocyte Col... Tacrolimus Cellcept	18 Years - 55 Years	Milton S. Hershey Medical Center

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