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Leukemia, Myeloid, AcutePhase 1NCT01390311

Azacitidine After Chemotherapy and Donor Lymphocyte Infusion in Patients With Relapsed Acute Myeloid Leukemia or Myelodysplastic Syndrome Previously Treated With Donor Stem Cell Transplant

A Phase 1 study testing Azacitidine, Pre-DLI Salvage Chemotherapy and Donor Leukocyte Infusion (DLI) in people with Leukemia, Myeloid, Acute and Myelodysplastic Syndromes, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial studies the effects and safety of adding azacitidine (5-AzaC) to the standard of care (Soc) for patients with relapsed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after being treated with donor stem cell transplant. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Azacitidine, Pre-DLI Salvage Chemotherapy and Donor Leukocyte Infusion (DLI)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteUnited States
Study dates
Apr 2012to Apr 2015
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

PATIENT Inclusion Criteria:

  • Must have a diagnosis of AML/MDS based on 2008 World Health Organization (WHO) classification of myeloid malignancies
  • Must have laboratory, histologic, or cytogenetic evidence of disease relapse after allogeneic hematopoietic stem cell transplant (HSCT) and require salvage therapy followed by DLI
  • Must have original donor
  • Must have life expectancy >= 2 months
  • Must be ≥ 18 years old. Azacitidine is not approved by the FDA for use in children
  • Must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 3
  • Must have laboratory results indicating:
  • Total bilirubin < 2.0 mg/dL
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 X the upper limit of institutional normal
  • Serum creatinine =< 2.0 mg/dL
  • Patient must have ability to understand and willingness to provide written informed consent prior to participation in the study and any related procedures being performed
  • The effects of 5-AzaC on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because category D agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of childbearing age must have a negative serum pregnancy test (Beta [B]-human chorionic gonadotropin) within 72 hours prior to initiating therapy and be willing to not become pregnant by using effective contraception while undergoing treatment and for at least 3 months afterwards; azacitidine is a pregnancy category D drug and could be harmful to or cause loss of a fetus; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Men must be willing not to father a new child while receiving therapy; they must use an effective barrier method of contraception during the study and for 3 months following the last dose
  • Both men and women and members of all races and ethnic groups are eligible for this trial

DONOR Inclusion Criteria:

  • Must be the original donor for the allogeneic bone marrow transplant patient
  • Must have signed the standard informed consent form; if sufficient cryopreserved cells remain from a previous donation, no additional donation or consent is required
  • Must be eligible according to Washington University "Guidelines for Eligibility of Normal Donors" or per National Marrow Donor Program (NMDP) standards if unrelated donor
  • Both men and women and members of all races and ethnic groups are eligible for this trial

PATIENT Exclusion Criteria:

  • Must not have Grade III-IV GVHD
  • Must not have an advanced malignant hepatic tumor
  • Must not receive anti-thymocyte globulin, campath (alemtuzumab) or daclizumab within 4 weeks of DLI
  • Must not receive any other forms of chemotherapy after cell infusion during the treatment protocol
  • Must not be receiving any other investigational agents within 14 days of first dose of study drug
  • Must not have uncontrolled intercurrent illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
  • Must not be pregnant or breastfeeding; pregnant women are excluded from this study because azacitidine is a Category D agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with azacitidine, breastfeeding should be discontinued if the mother is treated with azacitidine; these potential risks may also apply to other agents used in this study
  • Must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to azacitidine or other agents used in the study
  • Must not have a known or suspected hypersensitivity to azacitidine or mannitol.
  • Must not be human immunodeficiency virus (HIV)-positive and on combination antiretroviral therapy; these patients are ineligible because of the potential for pharmacokinetic interactions with azacitidine; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated

DONOR Exclusion Criteria:

  • Must not have any underlying conditions which would contra-indicate apheresis
  • Must not be pregnant

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 Study of the Safety and Feasibility of Azacitidine After Donor Lymphocyte Infusion for Patients With Relapsed Acute Myeloid Leukemia or Myelodysplastic Syndrome After Allogeneic Stem Cell Transplantation

This phase I trial studies the effects and safety of adding azacitidine (5-AzaC) to the standard of care (Soc) for patients with relapsed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after being treated with donor stem cell transplant. SoC includes giving an infusion of the donor's white blood cells (donor lymphocyte infusion or DLI) to boost the anticancer effects of the transplant. Giving 5-AzaC after DLI may alter the function of T-cells resulting in reduced incidence of graft versus host disease (GVHD) while maintaining the anticancer effects.

Read the detailed description

PRIMARY OBJECTIVES:

-To determine the Maximum Tolerated Dose (MTD) of 5-AzaC (azacitidine) when given after chemotherapy and DLI in patients with AML/MDS who relapse after allogeneic stem cell transplant.

SECONDARY OBJECTIVES:

  • To determine the rate of Grades II-IV and III-IV acute GVHD (aGVHD) in first 100 days after DLI.
  • To determine the rates of complete remission (CR), partial remission, (PR) and complete remission with incomplete count recovery (CRi), and overall response rate (CR+ CRi + PR).
  • To determine overall survival 100 days after DLI.
  • To determine the effects of increasing dose of 5-AzaC on frequency and absolute number of resting regulatory T-cells (rTregs) and activated Tregs (aTregs) at baseline, 7 days, 14 days, 21 days, and ~60 days after first dose of 5-AzaC.
Being tested
Azacitidine, Pre-DLI Salvage Chemotherapy, Donor Leukocyte Infusion (DLI)
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

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

  • AzacitidineDrug

    Also called 5-AC, 5-azacytidine, azacytidine, Vidaza

  • Pre-DLI Salvage ChemotherapyDrug

    At the discretion of the treating physician

  • Donor Leukocyte Infusion (DLI)Biological

Study groups in NCT01390311
Study groupRoleWhat they receive
Control CohortActive comparator1. Pre-DLI Salvage Chemotherapy (at the discretion of the treating physician) 2. DLI will be administered 2 +/- 1 weeks after pre-DLI chemotherapy. The minimum CD3+ cell counts in DLI product should be 1 x 107 cells/kg for sibling and ~1 x 106/kg for match unrelated donors based on recipient weight 3. No Azacitidine will be given
Receives: Drug: Pre-DLI Salvage Chemotherapy; Biological: Donor Leukocyte Infusion (DLI)
Cohort 1 (Starting Dose)Experimental1. Pre-DLI Salvage Chemotherapy (at the discretion of the treating physician) 2. DLI will be administered 2 +/- 1 weeks after pre-DLI chemotherapy. The minimum CD3+ cell counts in DLI product should be 1 x 107 cells/kg for sibling and ~1 x 106/kg for match unrelated donors based on recipient weight 3. Azacitidine 45 mg/m2 IV on Days 4, 6, 8, and 10 post-DLI.
Receives: Drug: Azacitidine; Drug: Pre-DLI Salvage Chemotherapy; Biological: Donor Leukocyte Infusion (DLI)
Cohort 2Experimental1. Pre-DLI Salvage Chemotherapy (at the discretion of the treating physician) 2. DLI will be administered 2 +/- 1 weeks after pre-DLI chemotherapy. The minimum CD3+ cell counts in DLI product should be 1 x 107 cells/kg for sibling and ~1 x 106/kg for match unrelated donors based on recipient weight 3. Azacitidine 75 mg/m2 IV on Days 4, 6, 8, and 10 post-DLI.
Receives: Drug: Azacitidine; Drug: Pre-DLI Salvage Chemotherapy; Biological: Donor Leukocyte Infusion (DLI)

What is being measured

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

  1. MTD and DLT of azacitidine when given after DLI

    MTD is defined as the maximum dose level immediately below the dose level at which 2 patients of a cohort (3 to 6 patients) experience dose-limiting toxicity during the first cycle.

    Measured: 40 days (after DLI)

Secondary outcomes (4)
  1. Rate of Grade II-IV and III-IV acute GVHD based on Glucksberg criteria

    Measured: 100 days (after DLI)

  2. Rates of CR, CRi, PR, and overall response (CR+CRi+PR = overall response)

    Measured: 1 year (after DLI)

  3. Overall survival

    Measured: 100 days (after DLI)

  4. Effects of increasing dose of azacitidine on frequency and absolute number of (resting T-cells) rTregs and (T-cells)Tregs

    Measured: 64 days (Baseline, 7 days, 14 days, 21 days, and ~60 days after first dose of azacitidine

Timeline

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

  1. First posted11 Jul 2011 (estimated)
  2. Study startApr 2012
  3. Primary completionMar 2014
  4. Study completionApr 2015

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01390311
Sponsor's protocol ID
201108380
Other IDs
NCI-2011-01077
Status last verified
Apr 2015
First submitted
23 Jun 2011
Last updated
27 Apr 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Azacitidine, Pre-DLI Salvage Chemotherapy and Donor Leukocyte Infusion (DLI) in people with Leukemia, Myeloid, Acute and Myelodysplastic Syndromes, 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?

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: finished, as of the sponsor's last update on 27 Apr 2015. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

MTD and DLT of azacitidine when given after DLI (time frame: 40 days (after DLI)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 27 Apr 2015.

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