Allogeneic or Haploidentical Stem Cell Transplant Followed By High-Dose Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

NCT02057770 | Terminated Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 201401080
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (1)

• Event Free Survival (EFS) rate

  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.

  Assessed at 100 days post-transplant

Secondary Outcomes (8)

• Overall Survival (OS)

  Assessed at 1 year post-transplant

• Rate of Leukemia Free Survival (LFS)

  Assessed at 100 days post-transplant

• Transplant Related Mortality (TRM) Rate

  Assessed at 100 days post-transplant

• Time to neutrophil engraftment

  Assessed up to day 30

• Incidence of acute GVHD

  Up to 100 days post-transplant

Study Arms (2)

Treatment (preparative regimen, transplant, cyclophosphamide)

EXPERIMENTAL

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.

Drug: busulfan; Drug: fludarabine phosphate; Radiation: total-body irradiation (TBI); Procedure: Stem cell transplant; Drug: cyclophosphamide

CRS preventive regimen

EXPERIMENTAL

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.

Drug: tocilizumab

Interventions

busulfan DRUG

Also known as: Myleran®

Treatment (preparative regimen, transplant, cyclophosphamide)

fludarabine phosphate DRUG

Also known as: Fludara®, 2-Fluoro-ara-A Monophosphate, 2-Fluoro-ara AMP, FAMP

Treatment (preparative regimen, transplant, cyclophosphamide)

total-body irradiation (TBI) RADIATION

Treatment (preparative regimen, transplant, cyclophosphamide)

Stem cell transplant PROCEDURE

Treatment (preparative regimen, transplant, cyclophosphamide)

cyclophosphamide DRUG

Also known as: Cytoxan®, CPM, CTX, CYT

Treatment (preparative regimen, transplant, cyclophosphamide)

tocilizumab DRUG

Also known as: anti-IL-6 monoclonal antibody, Actemra

CRS preventive regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 %

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Busulfan; fludarabine phosphate; FAMP protocol; Whole-Body Irradiation; Stem Cell Transplantation; Cyclophosphamide; tocilizumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Todd Fehniger, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2014
• First Posted: February 7, 2014
• Study Start: February 28, 2014
• Primary Completion: January 12, 2018
• Study Completion: March 23, 2018
• Last Updated: October 12, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)