Clinical trial NCT02057770: Allogeneic or Haploidentical Stem Cell Transplant Followed By High-Dose Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
Official title: A Pilot Study of Myeloablative Allogeneic or Haploidentical Stem Cell Transplantation With High Dose PT-Cy in Relapsed/Refractory AML
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Leukemia, Myeloid, Acute
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2014-02-07
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to look at overall health status and how acute myeloid leukemia (AML) responds to a stem cell transplant when followed with cyclophosphamide. Some participants enrolling in this study may receive a transplant from a sibling, some may receive a transplant from a matched unrelated donor, and some may receive what is called a haploidentical transplant. A haploidentical stem cell transplant is a type of transplant that occurs when a person who needs a transplant cannot find a donor who exactly matches their tissue type (either among family members or through a matched unrelated donor). When no matched donor is available, half-matched related (haploidentical) donors may be used. Haploidentical donors are first degree relatives such as siblings, children, or parents.

People who undergo a stem cell transplant can experience complications such as rejection of the stem cell transplant or severe graft-versus-host disease (GVHD). GVHD occurs when some of the cells from the donor attack the recipient's tissues, resulting in mild, moderate, or even life-threatening side effects to the recipient's skin, stomach, intestines, and liver. However, recent research has shown that receiving cyclophosphamide after stem cell transplant can improve the outcomes of the transplant, and that is the purpose of this study.


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.

Primary outcomes:
measure: Event Free Survival (EFS) rate
timeFrame: Assessed at 100 days post-transplant
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Assessed at 1 year post-transplant
measure: Rate of Leukemia Free Survival (LFS)
timeFrame: Assessed at 100 days post-transplant
measure: Transplant Related Mortality (TRM) Rate
timeFrame: Assessed at 100 days post-transplant
measure: Time to neutrophil engraftment
timeFrame: Assessed up to day 30
measure: Incidence of acute GVHD
timeFrame: Up to 100 days post-transplant
measure: Incidence of chronic GVHD
timeFrame: 1 year post-transplant starting at day +100
measure: Time to platelet engraftment
timeFrame: Assessed up to day 100
measure: Rate of CRS with and without tocilizumab prophylaxis
timeFrame: Assessed up to day 7
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Todd Fehniger, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: