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Leukemia, Myeloid, AcutePhase 1NCT02057770

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

A Phase 1 study testing busulfan, fludarabine phosphate and total-body irradiation (TBI) in people with Leukemia, Myeloid, Acute, run by Washington University School of Medicine at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia, Myeloid, Acute
What is being tested?
busulfan, fludarabine phosphate and total-body irradiation (TBI)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
28 Feb 2014to 23 Mar 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 24Show fewer
  • 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)

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

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

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.

Being tested
busulfan, fludarabine phosphate, total-body irradiation (TBI), Stem cell transplant, cyclophosphamide
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • busulfanDrug

    Also called Myleran®

  • fludarabine phosphateDrug

    Also called Fludara®, 2-Fluoro-ara-A Monophosphate, 2-Fluoro-ara AMP, FAMP

  • total-body irradiation (TBI)Radiation

  • Stem cell transplantProcedure or surgery

  • cyclophosphamideDrug

    Also called Cytoxan®, CPM, CTX, CYT

  • tocilizumabDrug

    Also called anti-IL-6 monoclonal antibody, Actemra

Study groups in NCT02057770
Study groupRoleWhat they receive
Treatment (preparative regimen, transplant, cyclophosphamide)ExperimentalBUSULFAN 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.
Receives: Drug: busulfan; Drug: fludarabine phosphate; Radiation: total-body irradiation (TBI); Procedure: Stem cell transplant; Drug: cyclophosphamide
CRS preventive regimenExperimentalThe 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.
Receives: Drug: tocilizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Assessed at 100 days post-transplant

Secondary outcomes (8)

  1. 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.

    Measured: Assessed at 1 year post-transplant

  2. 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.

    Measured: Assessed at 100 days post-transplant

  3. 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.

    Measured: Assessed at 100 days post-transplant

  4. 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.

    Measured: Assessed up to day 30

  5. Incidence of acute GVHD

    The incidence and severity of acute GVHD will be determined. Rates will be calculated with exact 95% confidence intervals.

    Measured: Up to 100 days post-transplant

  6. Incidence of chronic GVHD

    The incidence and severity of chronic GVHD will be determined. Rates will be calculated with exact 95% confidence intervals.

    Measured: 1 year post-transplant starting at day +100

  7. 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.

    Measured: Assessed up to day 100

  8. 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

    Measured: Assessed up to day 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Feb 2014 (estimated)
  2. Study start28 Feb 2014
  3. Primary completion12 Jan 2018
  4. Study completion23 Mar 2018

Why it stopped: Low accrual rate

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02057770
Sponsor's protocol ID
201401080
Status last verified
Oct 2018
First submitted
5 Feb 2014
Last updated
12 Oct 2018
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing busulfan, fludarabine phosphate and total-body irradiation (TBI) in people with Leukemia, Myeloid, Acute, run by Washington University School of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Low accrual rate). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event Free Survival (EFS) rate (time frame: Assessed at 100 days post-transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02057770.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2018.

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