Trial record 1 of 1 for:    NCT02057770
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Allogeneic or Haploidentical Stem Cell Transplant Followed By High-Dose Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT02057770
First received: February 5, 2014
Last updated: September 15, 2014
Last verified: September 2014
  Purpose

This pilot clinical trial studies how overall health status and how disease responds to a type of transplant called a haploidentical stem cell transplant when followed with a couple of doses of a drug called cyclophosphamide in patients with acute myeloid leukemia that has relapsed after a complete remission or that has never fully responded to therapy. When a patient cannot find a donor who exactly matches their tissue type, half-matched related (haploidentical) donors, who are first degree relatives such as siblings, children, or parents, may be used. In the past, people who have undergone haploidentical stem cell transplant have been more likely to experience complications such as rejection of the stem cell transplant or severe graft-versus host disease (GVHD). Giving cyclophosphamide after haploidentical stem cell transplant may improve the outcomes of the transplant.


Condition Intervention
Leukemia, Myeloid, Acute
Drug: busulfan
Drug: fludarabine phosphate
Radiation: total-body irradiation (TBI)
Procedure: allogeneic hematopoietic stem cell transplantation
Drug: cyclophosphamide

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Myeloablative Allogeneic or Haploidentical Stem Cell Transplantation With High Dose PT-Cy in Relapsed/Refractory AML

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Event Free Survival (EFS) rate [ Time Frame: Assessed at 100 days post-transplant ] [ Designated as safety issue: No ]
    The time from date of first dose of the preparative regimen until failure to engraft, treatment failure, disease progression/relapse, or death from any cause (whichever occurs first). Rates will be calculated with exact 95% confidence intervals.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Assessed at 1 year post-transplant ] [ Designated as safety issue: No ]
    The time from the date of day 0 until death from any cause. Rates will be calculated with exact 95% confidence intervals.

  • Rate of Leukemia Free Survival (LFS) [ Time Frame: Assessed at 100 days post-transplant ] [ Designated as safety issue: No ]
    The time from date of day 0 until disease progression or death from any cause (whichever occurs first). Rates will be calculated with exact 95% confidence intervals. For patients who achieve CR, CRc, or CRi only.

  • Transplant Related Mortality (TRM) Rate [ Time Frame: Assessed at 100 days post-transplant ] [ Designated as safety issue: No ]
    Death from causes other than disease relapse or progression prior to Day +100 visit. Rates will be calculated with exact 95% confidence intervals.

  • Time to neutrophil engraftment [ Time Frame: Assessed up to day 30 ] [ Designated as safety issue: No ]
    Defined as an untransfused platelet measurement > 20,000/ x10^9/L x 3 consecutive days. Kaplan-Meier models will be used to estimate median time to platelet engraftment and plot a time to event curve. Cox proportional hazards models may be used to explore the effect of covariates on time to platelet engraftment.

  • Incidence of acute GVHD [ Time Frame: Up to 100 days post-transplant ] [ Designated as safety issue: No ]
    The incidence and severity of acute GVHD will be determined. Rates will be calculated with exact 95% confidence intervals.

  • Incidence of chronic GVHD [ Time Frame: 1 year post-transplant starting at day +100 ] [ Designated as safety issue: No ]
    The incidence and severity of chronic GVHD will be determined. Rates will be calculated with exact 95% confidence intervals.

  • Time to platelet engraftment [ Time Frame: Assessed up to day 100 ] [ Designated as safety issue: No ]
    Defined as an untransfused platelet measurement > 20,000/ x10^9/L x 3 consecutive days. Kaplan-Meier models will be used to estimate median time to platelet engraftment and plot a time to event curve. Cox proportional hazards models may be used to explore the effect of covariates on time to platelet engraftment.

  • Impact of donor type on patient outcome [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
    To determine the impact of donor type (HLA-matched sibling v. HLA-matched unrelated v. HLA-haploidentical) in the outcomes of patients with active AML who undergo transplantation


Estimated Enrollment: 60
Study Start Date: February 2014
Estimated Study Completion Date: May 2020
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (preparative regimen, transplant, cyclophosphamide)

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 -7 to -5 and undergo TBI twice daily on days -4 to -1.

AND

DONOR CELL INFUSION: Patients undergo haploidentical donor stem cell transplant on day 0.

AND

POST-TRANSPLANT CYCLOPHOSPHAMIDE: Patients receive cyclophosphamide IV over 90 minutes on days 3 and 4.

Drug: busulfan
Other Name: Myleran®
Drug: fludarabine phosphate
Other Names:
  • Fludara®
  • 2-Fluoro-ara-A Monophosphate
  • 2-Fluoro-ara AMP, FAMP
Radiation: total-body irradiation (TBI) Procedure: allogeneic hematopoietic stem cell transplantation Drug: cyclophosphamide
Other Names:
  • Cytoxan®
  • CPM
  • CTX
  • CYT

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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, etc)
  • Available HLA-matched sibling donor that meets the following criteria:

    • At least 18 years of age
    • HLA donor/recipient match based on 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
    • Negative for hepatitis, HTLV, and HIV
    • Not pregnant OR
  • Available HLA-matched unrelated donor that meets the following criteria:

    • At least 18 years of age
    • HLA donor/recipient match by high-resolution typing at the A, B, C, and DRB1 locus
    • In the investigator's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting HSC
    • Negative for hepatitis, HTLV, and HIV
    • Not pregnant OR
  • 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
    • Negative for hepatitis, HTLV, and HIV
    • Not pregnant
  • 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
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02057770

Contacts
Contact: Rizwan Romee, M.D. 314-747-1385 rromee@dom.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Rizwan Romee, M.D.    314-747-1385    rromee@dom.wustl.edu   
Sub-Investigator: Jesse Keller, M.D.         
Sub-Investigator: John DiPersio, M.D., Ph.D.         
Sub-Investigator: Peter Westervelt, M.D., Ph.D.         
Sub-Investigator: Todd Fehniger, M.D., Ph.D.         
Sub-Investigator: Camille Abboud, M.D., Ph.D.         
Sub-Investigator: Amanda Cashen, M.D.         
Sub-Investigator: Meagan Jacoby, M.D., Ph.D.         
Sub-Investigator: Iskra Pusic, M.D.         
Sub-Investigator: Mark Schroeder, M.D.         
Sub-Investigator: Keith Stockerl-Goldstein, M.D.         
Sub-Investigator: Geoffrey Uy, M.D.         
Sub-Investigator: Ravi Vij, M.D.         
Sub-Investigator: Kristan Augustin, PharmD         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Rizwan Romee, M.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02057770     History of Changes
Other Study ID Numbers: 201401080
Study First Received: February 5, 2014
Last Updated: September 15, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Fludarabine phosphate
Busulfan
Fludarabine
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 18, 2014