Trial record 1 of 1 for:    NCT01747499
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Azacitidine in Patients Undergoing Matched Unrelated Stem Cell Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01747499
First received: December 7, 2012
Last updated: October 1, 2014
Last verified: October 2014
  Purpose

The purpose of this phase I/II study is to define the maximum tolerated dose of 5-AzaC and the effect on grade II-IV GvHD when given after matched unrelated donor transplant (MUD).


Condition Intervention Phase
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Drug: Azacitidine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Intravenous Azacitidine in Patients Undergoing Matched Unrelated Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Phase I: to determine the maximum tolerated dose (MTD) of azacitidine in patients undergoing matched (8 out of 8) unrelated donor transplant for any hematological malignancy in remission or with stable disease. [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Tolerability of azacitidine will be assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  • Phase II: to determine the effect of azacitidine on grade II-IV GvHD in patients undergoing matched (8 out of 8) unrelated donor transplant for AML in remission 1 or 2 or MDS. [ Time Frame: Day +100 ] [ Designated as safety issue: Yes ]
    GVHD rate and severity will be assessed based on modified Glucksberg criteria. Grade II-IV and III-IV aGVHD in first 100 days after transplant will be assessed.


Secondary Outcome Measures:
  • Rate of Grades III-IV aGVHD at Day +180. [ Time Frame: Day 180 ] [ Designated as safety issue: Yes ]
    GVHD rate and severity will be assessed based on modified Glucksberg criteria.

  • Overall survival [ Time Frame: One year after transplant ] [ Designated as safety issue: No ]
    Date of transplant to the date of death from any cause.

  • Treatment-related mortality [ Time Frame: Day +100 ] [ Designated as safety issue: No ]
    Death that results from a transplant procedure-related complication (e.g. infection, organ failure, hemorrhage, GVHD) rather than from relapse of the underlying disease or an unrelated cause.

  • Rate of relapse-free survival [ Time Frame: One year after transplant ] [ Designated as safety issue: No ]
    Recurrence of the original malignant disease after transplantation. The time to relapse is the time to the first observation of hematologic, radiographic, or cytogenetic changes, which result in characterization as relapse.


Estimated Enrollment: 64
Study Start Date: April 2013
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1

Conditioning treatment

Transplant on Day 0

15 mg/m2 azacitidine Days 7-11

15 mg/m2 azacitidine Days 35-39

15 mg/m2 azacitidine Days 63-67

15 mg/m2 azacitidine Days 91-95

Drug: Azacitidine
Other Names:
  • Vidaza®
  • Ladakamycin
  • 5-AzaC
Experimental: Cohort 2

Conditioning treatment

Transplant on Day 0

30 mg/m2 azacitidine Days 7-11

30 mg/m2 azacitidine Days 35-39

30 mg/m2 azacitidine Days 63-67

30 mg/m2 azacitidine Days 91-95

Drug: Azacitidine
Other Names:
  • Vidaza®
  • Ladakamycin
  • 5-AzaC
Experimental: Cohort 3

Conditioning treatment

Transplant on Day 0

37.5 mg/m2 azacitidine Days 7-11

37.5 mg/m2 azacitidine Days 35-39

37.5 mg/m2 azacitidine Days 63-67

37.5 mg/m2 azacitidine Days 91-95

Drug: Azacitidine
Other Names:
  • Vidaza®
  • Ladakamycin
  • 5-AzaC
Experimental: Cohort 4

Conditioning treatment

Transplant on Day 0

45 mg/m2 azacitidine Days 7-11

45 mg/m2 azacitidine Days 35-39

45 mg/m2 azacitidine Days 63-67

45 mg/m2 azacitidine Days 91-95

Drug: Azacitidine
Other Names:
  • Vidaza®
  • Ladakamycin
  • 5-AzaC
Experimental: MTD Cohort

Conditioning treatment

Transplant on Day 0

Dose determined in Phase I - azacitidine Days 7-11

Dose determined in Phase I - azacitidine Days 35-39

Dose determined in Phase I - azacitidine Days 63-67

Dose determined in Phase I - azacitidine Days 91-95

Drug: Azacitidine
Other Names:
  • Vidaza®
  • Ladakamycin
  • 5-AzaC

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients must meet the following criteria within 30 days prior to Day 0 unless otherwise noted.

  • Phase I: Diagnosis of any hematological malignancy listed below (excluding myelofibrosis) in remission or with stable minimal residual disease

    • Acute myelogenous leukemia (AML) in 1st or subsequent remission or in relapse after any remission
    • Acute lymphoblastic leukemia (ALL) in 1st or subsequent remission or in relapse after any remission
    • Myelodysplastic syndrome either intermediate 1 or 2, or high risk by the International Prognostic Scoring System
    • Chronic myelogenous leukemia (CML) in accelerated or second chronic phase
    • Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete remission, partial remission, or refractory relapse
    • Chronic lymphocytic leukemia (CLL), Rai Stage 2-4, failing at least 2 prior regimens
    • Multiple myeloma (MM), Stage 2-3
    • Myeloproliferative disorder or neoplasm
  • Phase II: Diagnosis of AML in remission 1 or 2 or a diagnosis of myelodysplastic syndrome either intermediate 1 or 2, or high risk by the International Prognostic Scoring System.
  • Patients with MDS must be transplant candidates by current clinical standards.
  • Patients who have been treated with hypomethylating agents prior to entering the study are eligible.
  • Must have matched unrelated donor (8 of 8 HLA match at A, B, C, and DR loci) by high resolution DNA typing
  • Must have donor peripheral blood stem cells mobilized by NMDP standards. No bone marrow donors.
  • Must have 2-8 x 10^6 CD34+ cells/kg (recipient weight) infused on Day 0.
  • Must have at least one additional aliquot of >=1 x 10^6 CD34/kg cryopreserved cells stored at the time of transplant.
  • Must receive a myeloablative or reduced intensity conditioning regimen for SCT as defined by the CIBMTR

    • Cyclophosphamide and single dose total body irradiation
    • Fludarabine and busulfan
    • Fractionated TBI and cyclophosphamide
    • Busulfan and cyclophosphamide
  • Must be able to receive GVHD prophylaxis with tacrolimus and methotrexate.
  • Must be ≥ 18 yrs old and ≤ 70 yrs old. Azacitidine is not approved by the FDA for use in children.
  • Must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Must have laboratory results indicating:

    • Total bilirubin < 2.0 mg/dl, unless a diagnosis of Gilbert's disease
    • AST/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 azacitidine 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 (ß-human chorionic gonadotropin) within 72 hours prior to initiating the conditioning regimen and be willing to not become pregnant by using effective contraception while undergoing treatment and for at least 3 months after the last dose of azacitidine.
  • 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.

Exclusion Criteria:

  • Must not have myelofibrosis or other disease known to prolong neutrophil engraftment to > 28 days after transplant.
  • Must not be receiving any other investigational agents within 14 days of first dose of azacitidine (Day 7).
  • Must not have myeloablative conditioning as defined below:

    • TBI < or = Gy +/- purine analog
    • Flu + Cy +/- ATG
    • Flu + AraC + Ida
    • Cladribine + AraC
    • Total Lymphoid Irradiation + ATG
  • Must not receive antithymocyte globulin as part of pre-transplant conditioning regimens. Antithymocyte globulin is excluded due to its potential impact on modulating the incidence of GvHD or GvL.
  • 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 azacitidine. These potential risks may also apply to other agents used in this study.
  • Must not have a known or suspected hypersensitivity to azacitidine, mannitol, or compounds of similar composition to azacitidine..
  • Must not have an advanced malignant hepatic tumor.
  • Must not be HIV, HBV, or HCV positive.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01747499

Contacts
Contact: Mark A. Schroeder, M.D. 314-454-8304 mschroed@dom.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Mark A. Schroeder, M.D.    314-454-8304    mschroed@dom.wustl.edu   
Sub-Investigator: John DiPersio, M.D., Ph.D.         
Sub-Investigator: Peter Westervelt, M.D., Ph.D.         
Sub-Investigator: Linda Eissenberg, Ph.D.         
Sub-Investigator: Amanda Cashen, M.D.         
Sub-Investigator: Keith Stockerl-Goldstein, M.D.         
Sub-Investigator: Camille Abboud, M.D.         
Sub-Investigator: Ravi Vij, M.D.         
Sub-Investigator: Geoffrey Uy, M.D.         
Sub-Investigator: Michael Tomasson, M.D.         
Sub-Investigator: Matthew Walter, M.D.         
Sub-Investigator: Timothy Graubert, M.D.         
Sub-Investigator: A. Craig Lockhart, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Mark A. Schroeder, M.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01747499     History of Changes
Other Study ID Numbers: 201303012
Study First Received: December 7, 2012
Last Updated: October 1, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014