Azacitidine in Patients Undergoing Matched Unrelated Stem Cell Transplantation

NCT01747499 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2013030121P50CA171963-01A1
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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.

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

  28 days

• Phase II: Number of Participants With Grades II-IV Acute GvHD

  GVHD rate and severity will be assessed based on modified Glucksberg criteria. Grade II-IV and III-IV aGVHD in first 180 days after transplant will be assessed.

  Day +180

Secondary Outcomes (5)

• Rate of Grades III-IV aGVHD at Day +180.

  Day +180

• Overall Survival as Measured by Number of Participants Alive at 1 Year After Transplant

  One year after transplant

• Treatment-related Mortality

  Day +140

• Number of Participants Who Relapsed Within the First Year of Transplant

  Within the first year of transplant

• Rate of Chronic GvHD

  One year after transplant

Study Arms (5)

Cohort 1

EXPERIMENTAL

Conditioning treatment Transplant on Day 0 15 mg/m\^2 azacitidine Days 7-11 15 mg/m\^2 azacitidine Days 35-39 15 mg/m\^2 azacitidine Days 63-67 15 mg/m\^2 azacitidine Days 91-95

Drug: Azacitidine

Cohort 2

EXPERIMENTAL

Conditioning treatment Transplant on Day 0 30 mg/m\^2 azacitidine Days 7-11 30 mg/m\^2 azacitidine Days 35-39 30 mg/m\^2 azacitidine Days 63-67 30 mg/m\^2 azacitidine Days 91-95

Drug: Azacitidine

Cohort 3

EXPERIMENTAL

Conditioning treatment Transplant on Day 0 37.5 mg/m\^2 azacitidine Days 7-11 37.5 mg/m\^2 azacitidine Days 35-39 37.5 mg/m\^2 azacitidine Days 63-67 37.5 mg/m\^2 azacitidine Days 91-95

Drug: Azacitidine

Cohort 4

EXPERIMENTAL

Conditioning treatment Transplant on Day 0 45 mg/m\^2 azacitidine Days 7-11 45 mg/m\^2 azacitidine Days 35-39 45 mg/m\^2 azacitidine Days 63-67 45 mg/m\^2 azacitidine Days 91-95

Drug: Azacitidine

Phase II Cohort

EXPERIMENTAL

Conditioning treatment Transplant on Day 0 Dose determined in Phase I - 45 mg/m\^2 azacitidine Days 7-11 Dose determined in Phase I - 45 mg/m\^2 azacitidine Days 35-39 Dose determined in Phase I - 45 mg/m\^2 azacitidine Days 63-67 Dose determined in Phase I - 45 mg/m\^2 attitudinize Days 91-95

Drug: Azacitidine

Interventions

Azacitidine DRUG

Also known as: Vidaza®, Ladakamycin, 5-AzaC

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Phase II Cohort

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• The Foundation for Barnes-Jewish Hospital: collaborator
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

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

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Mark A. Schroeder, M.D.
• Organization: Washington University School of Medicine

markschroeder@wustl.edu

314-454-8304

Study Officials

• Mark A. Schroeder, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2012
• First Posted: December 11, 2012
• Study Start: April 15, 2013
• Primary Completion: August 31, 2018
• Study Completion: December 24, 2018
• Last Updated: October 16, 2019
• Results First Posted: October 16, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)