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 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
2 other identifiers
interventional
14
1 country
1
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Apr 2012
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 23, 2011
CompletedFirst Posted
Study publicly available on registry
July 11, 2011
CompletedStudy Start
First participant enrolled
April 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2015
CompletedApril 27, 2015
April 1, 2015
1.9 years
June 23, 2011
April 24, 2015
Conditions
Outcome Measures
Primary Outcomes (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.
40 days (after DLI)
Secondary Outcomes (4)
Rate of Grade II-IV and III-IV acute GVHD based on Glucksberg criteria
100 days (after DLI)
Rates of CR, CRi, PR, and overall response (CR+CRi+PR = overall response)
1 year (after DLI)
Overall survival
100 days (after DLI)
Effects of increasing dose of azacitidine on frequency and absolute number of (resting T-cells) rTregs and (T-cells)Tregs
64 days (Baseline, 7 days, 14 days, 21 days, and ~60 days after first dose of azacitidine
Study Arms (3)
Control Cohort
ACTIVE 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
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.
Cohort 2
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 75 mg/m2 IV on Days 4, 6, 8, and 10 post-DLI.
Interventions
At the discretion of the treating physician
Eligibility Criteria
You may qualify if:
- 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
- Must be the original donor for the allogeneic bone marrow transplant patient
- +3 more criteria
You may not qualify if:
- 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
- Must not have any underlying conditions which would contra-indicate apheresis
- Must not be pregnant
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Peter Westervelt, M.D., Ph.D.
Washington University School of Medicine
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 23, 2011
First Posted
July 11, 2011
Study Start
April 1, 2012
Primary Completion
March 1, 2014
Study Completion
April 1, 2015
Last Updated
April 27, 2015
Record last verified: 2015-04