Allogeneic or Haploidentical Stem Cell Transplant Followed By High-Dose Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
Leukemia, Myeloid, Acute
About this trial
This is an interventional treatment trial for Leukemia, Myeloid, Acute
Eligibility Criteria
Inclusion Criteria:
- AML without complete remission (CR/CRc/CRi) after at least 2 induction therapies OR
- AML that has relapsed within 6 months after obtaining a CR OR
- AML that has relapsed more than 6 months after obtaining a CR, and has treatment failure (TF) or progressive disease (PD) following at least 1 re-induction regimen OR
- AML that has relapsed post Allogeneic transplantation
- Active AML (bone marrow blasts ≥ 5% by morphology, staining, or flow) and/or presence of estramedullary disease
Available HLA-haploidentical donor that meets the following criteria:
- Blood-related family member (sibling (full or half), offspring, or parent, cousin, niece or nephew, aunt or uncle, or grandparent)
- At least 18 years of age
- HLA-haploidentical donor/recipient match by at least low-resolution typing per institutional standards
- In the investigator's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting HSC
- No active hepatitis
- Negative for HTLV and HIV
- Not pregnant
NOTE: there were HLA-matched sibling and HLA-matched unrelated donor cohorts, but those closed without completion of accrual with Amendment 11
- Karnofsky performance status ≥ 50 %
Adequate organ function as defined below:
- Total bilirubin ≤ 2.5 mg/dl (unless the patient has a history of Gilbert's syndrome)
- AST(SGOT) and ALT(SGPT) ≤ 3.0 x IULN
- Creatinine ≤ 2.0 x IULN OR estimated creatinine clearance ≥ 30 mL/min/1.73 m2 by Cockcroft-Gault Formula
- Oxygen saturation ≥ 90% on room air
- LVEF ≥ 40%
- FEV1 and FVC ≥ 40% predicted, DLCOc ≥ 40% predicted. If DLCO is < 40%, patients will still be considered eligible if deemed safe after a pulmonary evaluation.
- At least 18 years of age at the time of study registration
- Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable)
Exclusion Criteria:
- Circulating blast count ≥ 10,000/uL by morphology or flow cytometry (cytoreductive therapies including leukapheresis or hydroxyurea are allowed)
- Known HIV or Active hepatitis B or C infection
- Known hypersensitivity to one or more of the study agents
- Currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug (Day -7)
- Currently receiving or has received any intensive chemotherapy within the 14 days prior to the first dose of study drug (Day -7) (hydrea or other non-intensive regimens such as decitabine may be used but must stop at least one day prior to the first dose of study drug)
- Pregnant and/or breastfeeding
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements.
Sites / Locations
- Washington University School of Medicine
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Treatment (preparative regimen, transplant, cyclophosphamide)
CRS preventive regimen
BUSULFAN AND FLUDARABINE BASED PREPARATIVE REGIMEN: Patients receive busulfan IV over 3 hours on days -7 to -4, fludarabine phosphate IV over 30-60 minutes on days -6 to -2, and cyclophosphamide IV over 60 minutes on days -3 and -2. OR FLUDARABINE AND TBI BASED PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -4 and undergo TBI twice daily on days -3 to 0. AND DONOR CELL INFUSION: Patients undergo HLA-matched sibling stem cell transplant, HLA-matched unrelated, or HLA-haploidentical transplant on day 0. AND POST-TRANSPLANT CYCLOPHOSPHAMIDE: Patients receive cyclophosphamide IV over 90 minutes on days 3 and 4.
The final ~15 people enrolled who will be recipients of haploidentical transplants will receive tocilizumab IV over 60 minutes 6-12 hours prior to the start of the donor cell infusion.