Allogeneic Hematopoietic Stem Cell Transplantation as Initial Salvage Therapy for Patients with Primary Induction Failure Acute Myeloid Leukemia Refractory to High-Dose Cytarabine-Based Induction Chemotherapy
The goal of this research study is to learn if giving 1-2 courses of chemotherapy (decitabine, clofarabine, idarubicin, and cytarabine) followed by chemotherapy with busulfan, clofarabine, and fludarabine before an allogeneic stem cell transplant can help control AML that has not responded to treatment. The safety of this treatment will also be studied.
Disease Group: Blood And Marrow Transplantation,Leukemia
Treatment Agent: ATG,Busulfan,Clofarabine,Cyclophosphamide,Cytarabine,Decitabine,Fludarabine,Idarubicin,MESNA
Treatment Location: Only at MDACC
Primary Objectives: 1. To determine the safety and feasibility of allogeneic hematopoietic stem cell transplantation (AHSCT) as initial salvage treatment for patients with primary induction failure (PIF) acute myeloid leukemia (AML). 2. To determine efficacy of AHSCT following decitabine, clofarabine, idarubcine, and cytarabine (DCIA) salvage chemotherapy evaluated by overall response rate (RR), defined as complete response (CR) or CR without platelet recovery (CRp) or CR with insufficient hematological recovery (CRi). Secondary Objectives: 1. To determine the percentage of patients with PIF AML eligible for AHSCT after up to 2 courses of induction chemotherapy. 2. To determine the early treatment-related mortality (TRM) (within first 4 weeks of first salvage chemotherapy regimen with DCIA and day 100 TRM after AHSCT. 3. To determine the efficacy DCIA regimen as salvage chemotherapy for patients with PIF AML (% of patients who achieve
IRB Review and Approval Date: 09/14/2015
Recruitment Status: Open
Projected Accrual: N/A
1) Patients age 18-60 years.
2) Patients with diagnosis of AML, judged primary refractory after up to 2 courses of AML induction therapy (> 5% blasts on day 21 (+/-7 days) bone marrow aspirate and/or biopsy from the beginning of induction chemotherapy, up to 42 days).
3) Eastern Cooperative Oncology Group (ECOG) Performance Status </= 2.
4) Adequate major organ function:, defined as: a) Serum creatinine </= 3 mg/dL; b) Total bilirubin </= 2.5 mg/dL; c) ALT (SGPT) </= 3 x ULN or </= 5 x ULN if related to disease; d) Cardiac ejection fraction >/= 40% (by either ECHO or MUGA).
5) Willingness to have an allogeneic transplant.
6) Patient or patient’s legal representative able to provide written informed consent.
7) Patients are required to meet the following criteria to proceed to AHSCT:
8) Donor criteria: Availability of a donor either an HLA matched sibling donor (MSD) or a haploidentical (5-9/10 HLA matched); alternatively a 8/8 HLA matched unrelated donor (MUD) by high resolution typing is immediately available;
9) Disease criteria: Day 21 (+/-7 days) bone marrow aspiration or biopsy from the beginning of salvage DCIA: a. In complete morphologic remission with <5% bone marrow blasts, or b. Aplastic (<10% bone marrow cellularity), and cytopenic with an absolute neutrophil count (ANC) less than 1,000/µL, or c. Low disease burden with < 30% BM blasts, with recovery of peripheral blood (PB) WBC (ANC>1,000/µL) and <5% circulating blasts.
10) Adequate organ function criteria: a. Serum creatinine clearance >/= 50 ml/min (calculated by Cockroft-Gault formula); b. Total bilirubin </= 2 times upper limit of normal (x ULN) (3 x ULN if considered to be due to leukemic involvement or Gilbert’s syndrome); c. Alanine aminotransferase (ALT) </= 3 x ULN (5.0 x ULN if considered to be due to leukemic involvement); d. LVEF >/= 40% on ECHO or MUGA; e. DLCO >/= 50% predicted after correction for hemoglobin (must be performed in patients with history of smoking or lung disease;); DLCO may be omitted in patients without history of pulmonary disease if approved by the Study Chair.
11) No active infection: Patients should be afebrile. If present, pulmonary infiltrates or other sites of infection must be improving on antibiotics. Patients should not require oxygen. Study Chair will be the arbiter of this criterion.
1) HIV positive; active hepatitis B or C.
2) Uncontrolled active infections (viral, bacterial, and fungal); the Study Chair will be the final arbiter of this criterion.
3) Patients with active secondary malignancy unless approved by the Study Chair.
4) Liver cirrhosis.
5) Active CNS involvement within the previous 2 months.
6) Prior induction therapy with DAC + CIA.
7) Positive pregnancy test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
8) Breast feeding women.
9) Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.
10) Inability to comply with medical therapy or follow-up.
Information and next steps
Blood And Marrow Transplantation,Leukemia
Stem Cell Transplantation and Cellular Therapy
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