Azacitidine in Treating Patients With Relapsed Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia Who Have Undergone Stem Cell Transplant

Treatment of Post-Transplant Relapse and Persistent Disease in Patients With MDS, CMML and AML With Azacitidine

This phase II trial studies how well azacitidine works in treating patients with relapsed myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML) who have undergone stem cell transplant. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Study Overview

• Status: Completed
• Conditions: Chronic Myelomonocytic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: azacitidine

Detailed Description

PRIMARY OBJECTIVES:

I. To improve overall survival in patients with post-transplant relapse of myeloid malignancies.

OUTLINE:

Patients receive azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• MDS, CMML or AML patients (as diagnosed by World Health Organization [WHO] criteria) with evidence of relapse or progression at >= day 28 and < day 100 post-transplant
• Recurrent or increased cytogenetic abnormalities by standard karyotype or fluorescence in situ hybridization (FISH) (the cytogenetic abnormalities must have been previously documented at some time point between diagnosis and date of stem cell transplant)
• Morphologic evidence of recurrence or increased abnormal myeloblasts in peripheral blood or marrow
• Flow Cytometric evidence of disease as determined by recurrent or increased abnormal myeloblasts in peripheral blood or marrow
• Extramedullary relapse (local radiotherapy will be allowed)
• MDS, CMML, or AML patients with persistent stable disease or persistent disease with regression at >= day 28 and < day 100 post-transplant; the inclusion of patients with persistent stable or persistent regressing disease in this protocol is not meant to advocate treatment; however, if the attending physician is inclined to offer treatment then these patients would be eligible for this study
• Persistence of cytogenetic abnormalities by standard karyotype or FISH
• Persistent morphologic evidence of abnormal myeloblasts (in patients with CMML the monoblastoid population is included) in peripheral blood or marrow
• Persistent flow cytometric evidence of abnormal myeloblasts (in patients with CMML the monoblastoid population is included) in peripheral blood or marrow
• Extramedullary persistence or regression

Exclusion Criteria:

• Refractory disease at time of stem cell transplant; patients who received chemotherapy prior to transplant with no evidence of response by International Working Group (IWG) criteria
• >= 10% bone marrow myeloblasts as measured by morphology
• Evidence of central nervous system (CNS) disease at time of relapse by morphology or flow (a diagnostic lumbar puncture [LP] is not required at time of relapse)
• Serum creatinine > 2 x ULN (upper limit of normal)
• Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) > 2x ULN
• Performance status > 2 (Eastern Cooperative Oncology Group [ECOG] Scale)
• Patients with severe disease other than MDS, CMML or AML which would be expected to prevent compliance with treatment
• Patients with severe infections (pneumonia, sepsis, etc) within the 2 weeks prior to the anticipated start of protocol treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (chemotherapy); Patients receive azacitidine SC or IV on days 1-7. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Drug: azacitidine; Given SC or IV; Other Names: 5-AC; Vidaza; 5-azacytidine; azacytidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Count of surviving participants at 6 months.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Response by IWG Criteria	Count of participants achieving a complete or partial remission at 6 months.	6 months
Incidence of Grades II-IV Graft-versus-host Disease (GVHD)		6 months

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI); Celgene Corporation
• Investigators: Principal Investigator: Bart Scott, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: March 8, 2010
• First Submitted That Met QC Criteria: March 8, 2010
• First Posted (Estimate): March 10, 2010

Study Record Updates

• Last Update Posted (Actual): May 24, 2017
• Last Update Submitted That Met QC Criteria: April 17, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic-Myeloproliferative Diseases; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Recurrence; Preleukemia; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: 2240.00 (Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium); P30CA015704 (U.S. NIH Grant/Contract); P01CA078902 (U.S. NIH Grant/Contract); NCI-2010-00281 (Registry Identifier: CTRP (Clinical Trial Reporting Program))