AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 1NCT02750254

Azacitidine in Haploidentical Donor Hematopoietic Cell Transplantation

A Phase 1 study testing Fludarabine, Fractionated total body irradiation and Busulfan in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, 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
Search all trials

Trial summary

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for patients with hematologic malignancies including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and acute lymphoblastic leukemia (ALL); however, human leukocyte antigen (HLA)-matched donor availability… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Fludarabine, Fractionated total body irradiation and Busulfan
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
27 Jun 2016to 14 Oct 2020
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

  • Diagnosis of acute leukemia (AML/ALL) or advanced MDS (INT-2 or high risk) in complete remission (CR/CRc/CRi) documented by bone marrow biopsy done within 30 days prior to the initiation of conditioning regimen.
  • Available HLA-haploidentical donor that meets the following criteria:
  • Immediate family member (sibling, offspring, or parent)
  • At least 18 years of age
  • HLA-haploidentical donor/recipient match by class I serologic typing at the A\&B locus.
  • In the treating physician's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting HSC
Show all 18Show fewer
  • No active hepatitis (B, C), HTLV, and HIV infections
  • Not pregnant
  • Karnofsky performance status ≥ 70 %
  • 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 m^2 by Cockcroft-Gault Formula
  • Oxygen saturation ≥ 90% on room air
  • LVEF ≥ 40%
  • FEV1 and FVC ≥ 50% predicted, corrected DLCO ≥ 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)

Who cannot join

  • Recipients with donor sensitive antibodies (DSA), defined by 2000 or higher MFI against one or more class I or II antigens
  • Known HIV or active Hepatitis B or C infection
  • Underwent a previous related or unrelated allogeneic transplant
  • 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 the conditioning regimen.
  • Pregnant and/or breastfeeding
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or unstable cardiac arrhythmias.
  • Presence of a readily available 6/6 matched sibling donor who is a candidate for donation

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 Phase I/II Study of Azacitidine in Haploidentical Donor Hematopoietic Cell Transplantation

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for patients with hematologic malignancies including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and acute lymphoblastic leukemia (ALL); however, human leukocyte antigen (HLA)-matched donor availability continues to be a major hurdle. Historically, HLA haploidentical donor hematopoietic cell transplantation (haplo-HCT) was associated with high incidences of graft rejection and excessive non-relapse mortality (NRM), but recent advances utilizing post-transplant cyclophosphamide (PT-Cy) have revolutionized haplo-HCT and the outcomes are now comparable to allo-HCT using more traditional HLA matched related and unrelated donors. However, graft-versus-host disease (GvHD) continues to be a problem and is associated with significant morbidity and mortality in allo-HCT patients including those who receive haplo-HCT on PT-Cy platform. The aim of this early phase study is to investigate the safety and overall efficacy of azacitidine in reducing the incidence and severity of GvHD when added to PT-Cy based haplo-HCT platform for patients with AML, ALL, or advanced MDS.

Being tested
Fludarabine, Fractionated total body irradiation, Busulfan, Cyclophosphamide, Single dose total body irradiation
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

  • FludarabineDrug

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

  • Fractionated total body irradiationRadiation

  • BusulfanDrug

    Also called Myerlan, Busulphan

  • CyclophosphamideDrug

    Also called Cytoxan, CPM, CTX, CYT

  • Single dose total body irradiationRadiation

  • MelphalanDrug

    Also called Alkeran, Phenylalanine mustard

  • Granulocyte-colony stimulating factorDrug

    Also called G-CSF, Plerixafor, Mozobil, Neupogen

  • Stem cell transplantProcedure or surgery

  • AzacitidineDrug

    Also called Vidaza, Ladakamycin

Study groups in NCT02750254
Study groupRoleWhat they receive
Arm 1: AzacitidineExperimental* Treating physician must choose from one of these conditioning regimens (will be given per standard of care) * fludarabine and fractionated total body irradiation (Flu/FrTBI) * fludarabine and busulfan (Flu/Bu4) * fludarabine, cyclophosphamide, and single dose total body irradiation (Flu/Cy/sdTBI) * fludarabine and melphalan (Flu/Mel) * reduced-intensity fludarabine and busulfan (Flu/Bu2) * G-CSF from Day -5 through Day -1 per standard of care * On Day 0, the allograft will be infused per standard of care. * Azacitidine will be administered on Day +1 and +2 post-stem cell transfusion days * Cyclophosphamide on Days +3 and +4 post-transplant
Receives: Drug: Fludarabine; Radiation: Fractionated total body irradiation; Drug: Busulfan; Drug: Cyclophosphamide; Radiation: Single dose total body irradiation; Drug: Melphalan; Drug: Granulocyte-colony stimulating factor; Procedure: Stem cell transplant; Drug: Azacitidine

What is being measured

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

  1. Safety of azacitidine (Phase I only) as measured by frequency and grade of adverse events

    The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

    Measured: Up to Day 35

  2. Maximum tolerated dose of azacitidine (Phase I only)

    Measured: Estimated to be 3-4 months (completion of all Phase I patients through Day 35)

  3. Grade II-IV acute GvHD rate of azacitidine (Phase II only)

    Measured: Up to Day 100

Secondary outcomes (8)

  1. Event-free survival (EFS)

    EFS is defined as 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).

    Measured: Up to 48 months

  2. Overall survival (OS)

    OS is defined as the time from the date of Day 0 until death from any cause.

    Measured: Up to 48 months

  3. Disease-free survival (DFS)

    Measured: Up to 48 months

  4. Non-relapse mortality (NRM)

    NRM is defined as death that results from a transplant procedure-related complication (e.g. infection, organ failure, hemorrhage, GvHD) rather than from relapse of the underlying disease prior to Day +100 visit.

    Measured: Up to Day 100

  5. Time to neutrophil engraftment

    Time to neutrophil engraftment is measured by determining the first of 3 consecutive measurements of neutrophil count ≥ 500/ul following conditioning regimen-induced nadir.

    Measured: Up to 12 months

  6. Time to platelet engraftment

    Time to platelet engraftment is measured by determining the first of 3 consecutive measurements of platelet count ≥ 20,000/ul without platelet transfusion support for 7 days.

    Measured: Up to 12 months

  7. Rate of acute GvHD

    Incidence and severity of acute GvHD will be assessed based on the modified Glucksberg criteria and Seattle criteria. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s).

    Measured: Up to Day 100

  8. Rate of chronic GvHD

    Incidence and severity of chronic GvHD will be assessed based on the NIH consensus criteria and global severity scoring system. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s).

    Measured: Day 100 through Day 365

Timeline

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

  1. First posted25 Apr 2016 (estimated)
  2. Study start27 Jun 2016
  3. Primary completion24 May 2017
  4. Study completion14 Oct 2020

Why it stopped: Toxicity. Only enrolled patients in phase I portion of trial.

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02750254
Sponsor's protocol ID
201604081
Status last verified
Oct 2020
First submitted
18 Apr 2016
Last updated
20 Oct 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Fludarabine, Fractionated total body irradiation and Busulfan in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, 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 18 inclusion and 8 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 20 Oct 2020. 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: Toxicity. Only enrolled patients in phase I portion of trial.). 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?

Safety of azacitidine (Phase I only) as measured by frequency and grade of adverse events (time frame: Up to Day 35). The study lists 3 primary outcomes in all. 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 NCT02750254.

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 20 Oct 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in