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

Leukemia, Myeloid, Acute Clinical Trial

Official title:

A Pilot Study of Myeloablative Allogeneic or Haploidentical Stem Cell Transplantation With High Dose PT-Cy in Relapsed/Refractory AML

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02057770
• Other study ID #: 201401080
• Status: Terminated
• Phase: Phase 1
• Start date: February 28, 2014
• Est. completion date: March 23, 2018

Study information

• Verified date: October 2018
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: March 23, 2018
• Est. primary completion date: January 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• busulfan

• fludarabine phosphate

Radiation:
• total-body irradiation (TBI)

Procedure:
• Stem cell transplant

Drug:
• cyclophosphamide

• tocilizumab

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)	The time from the date of day 0 until death from any cause. Rates will be calculated with exact 95% confidence intervals.	Assessed at 1 year post-transplant
Secondary	Rate of Leukemia Free Survival (LFS)	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.	Assessed at 100 days post-transplant
Secondary	Transplant Related Mortality (TRM) Rate	Death from causes other than disease relapse or progression prior to Day +100 visit. Rates will be calculated with exact 95% confidence intervals.	Assessed at 100 days post-transplant
Secondary	Time to neutrophil engraftment	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.	Assessed up to day 30
Secondary	Incidence of acute GVHD	The incidence and severity of acute GVHD will be determined. Rates will be calculated with exact 95% confidence intervals.	Up to 100 days post-transplant
Secondary	Incidence of chronic GVHD	The incidence and severity of chronic GVHD will be determined. Rates will be calculated with exact 95% confidence intervals.	1 year post-transplant starting at day +100
Secondary	Time to platelet engraftment	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.	Assessed up to day 100
Secondary	Rate of CRS with and without tocilizumab prophylaxis	To investigate the rate of cytokine release syndrome with and without tocilizumab prophylaxis in patients with active AML who undergo haploidentical transplantation	Assessed up to day 7

External Links

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