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Phase II Randomized Study of Azacitidine With Versus Without MS-275 in Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia With Multilineage Dysplasia
Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information
Alternate Title
Azacitidine With or Without MS-275 in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia
Basic Trial Information
| Phase | Type | Status | Age | Protocol IDs |
|---|
| Phase II | Treatment | Active | 18 and over | ECOG-E1905
E1905, NCT00313586 |
Objectives Primary - Compare the overall response rate (complete, partial, and hematologic improvement-major
by International Working Group [IWG] criteria) in patients with myelodysplastic syndromes, chronic myelomonocytic leukemia (dysplastic), or acute myeloid leukemia with multilineage dysplasia treated with azacitidine with vs without MS-275.
- Compare the major response rate (complete and partial responses by IWG criteria) in patients treated with these regimens.
Secondary - Evaluate the toxicity of azacitidine and MS-275 in these patients.
- Identify changes in gene promoter methylation and gene expression that may be
associated with response to azacitidine and MS-275.
- Identify other molecular mechanisms (such as DNA damage) that may be
associated with response to azacitidine and MS-275.
Entry Criteria Disease Characteristics:
- Bone marrow aspirate and/or biopsy-confirmed diagnosis of 1 of the following:
- Myelodysplastic syndromes (MDS)
- Any International Prognostic Score (IPSS) eligible
- Patients with low or intermediate-1 IPSS must have platelet count < 50,000/mm³ and/or absolute neutrophil count < 500/mm³
- Blast count < 20%
- Chronic myelomonocytic leukemia (dysplastic subtype)
- WBC < 12,000/mm³ (measured twice within the past 4 weeks, 2 weeks apart)
- Acute myeloid leukemia with multilineage dysplasia (AML-TLD)
- Formerly diagnosed refractory anemia with excess blasts in transformation by FAB
criteria allowed
- AML-TLD by WHO criteria allowed in patients with no history of antecedent hematologic
disorder
- WBC ≤ 30,000/mm³ (measured twice within the past 4 weeks, 2 weeks apart)
- WBC that has doubled over 4 weeks AND > 20,000/mm³ is not eligible
- Evidence of ≥ 20% blasts on review of the bone marrow aspirate and/or biopsy
- SWOG patients must be enrolled in research study trial SWOG-9007
- No therapy-induced MDS or AML-TLD
- No clinical evidence of CNS or pulmonary leukostasis or disseminated
intravascular coagulation
- No clinical evidence of CNS leukemia
Prior/Concurrent Therapy:
- Recovered from prior therapy
- No prior azacitidine, decitabine or MS-275
- No prior induction chemotherapy for AML or stem cell transplantation
- No hematopoietic growth factors within 3 weeks prior to study entry
- No other concurrent investigational or commercial agents or therapies for the malignancy
- No concurrent valproic acid, epoetin alfa, or darbepoetin alfa
- No filgrastim (G-CSF) or pegfilgrastim during days 1-10 of each treatment course
Patient Characteristics:
- See Disease Characteristics
- ECOG performance status 0-2
- Life expectancy ≥ 6 months
- Creatinine < 2.0 mg/dL
- Bilirubin normal (unless due to intramedullary or extramedullary hemolysis, or Gilbert's syndrome)
- AST and ALT ≤ 2.5 times upper limit of normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active infections
- No advanced malignant hepatic tumors
- No other serious or uncontrolled medical conditions
- No known hypersensitivity to azacitidine or mannitol
Expected Enrollment 152A total of 152 patients will be accrued for this study. Outcomes Primary Outcome(s)The complete response rate, partial response rate, and trilineage response rate
Secondary Outcome(s)Overall response rate (complete response and partial response)
Toxicity
Clinical mechanism of azacitidine with or without MS-275 as measured by methylation-specific real time PCR (MSP) assay
Outline This is a randomized, multicenter study. Patients are stratified according to disease (myelodysplastic syndromes [MDS] high/intermediate-2 vs MDS low/intermediate-1 vs chronic myelomonocytic leukemia vs acute myeloid leukemia with multilineage dysplasia). Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive azacitidine subcutaneously once daily on days 1-10.
- Arm II: Patients receive azacitidine as in arm I and oral MS-275 on days 3 and 10.
Treatment in both arms repeats every 28 days for at least 6 and up to 24 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 5 years.
Trial Contact Information
Trial Lead Organizations Eastern Cooperative Oncology Group | | | | Steven Gore, MD, Protocol chair | | | | | Peter Greenberg, MD, Protocol co-chair | | | |
Trial Sites
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| U.S.A. |
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| Arizona |
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Scottsdale |
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| | | | | | | | | Mayo Clinic Scottsdale |
| | | Clinical Trials Office - All Mayo Clinic Locations | |
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| California |
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Stanford |
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| | | | Stanford Cancer Center |
| | | Clinical Trials Office - Stanford Cancer Center | |
| | Email:
cctoffice@stanford.edu |
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| Illinois |
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Alton |
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| | | | Saint Anthony's Hospital at Saint Anthony's Health Center |
| | | Bethany Sleckman, MD | |
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Berwyn |
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| | | Hematology Oncology Associates of Illinois - Berwyn |
| | | Martin Tallman, MD | |
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Chicago |
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| | | Hematology and Oncology Associates |
| | | Clinical Trails Office - Hematology and Oncology Associates | |
| | | Robert H. Lurie Comprehensive Cancer Center at Northwestern University |
| | | Clinical Trials Office - Robert H. Lurie Comprehensive Cancer Center at Northwestern University | |
| | Email:
cancer@northwestern.edu |
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Joliet |
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| | | Midwest Center for Hematology/Oncology |
| | | Martin Tallman, MD | |
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Libertyville |
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| | | North Shore Oncology and Hematology Associates, Limited - Libertyville |
| | | Martin Tallman, MD | |
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Mt. Vernon |
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| | | Good Samaritan Regional Health Center |
| | | Bethany Sleckman, MD | |
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Naperville |
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| | | La Grange Oncology Associates - Geneva |
| | | Martin Tallman, MD | |
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Niles |
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| | | Cancer Care and Hematology Specialists of Chicagoland - Niles |
| | | Martin Tallman, MD | |
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Rockford |
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| | | Swedish-American Regional Cancer Center |
| | | Clinical Trials Office - Swedish-American Regional Cancer Center | |
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Skokie |
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| | | Hematology Oncology Associates - Skokie |
| | | Martin Tallman, MD | |
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| Iowa |
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Ames |
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| | | | McFarland Clinic, PC |
| | | Clinical Trials Office - McFarland Clinic, PC | |
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Ottumwa |
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| | | McCreery Cancer Center at Ottumwa Regional |
| | | Robert Behrens | |
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| Kansas |
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Anthony |
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| | | | Hospital District Sixth of Harper County |
| | | Shaker Dakhil, MD, FACP | |
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Chanute |
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| | | Cancer Center of Kansas, PA - Chanute |
| | | Shaker Dakhil, MD, FACP | |
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Dodge City |
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| | | Cancer Center of Kansas, PA - Dodge City |
| | | Shaker Dakhil, MD, FACP | |
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El Dorado |
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| | | Cancer Center of Kansas, PA - El Dorado |
| | | Shaker Dakhil, MD, FACP | |
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Fort Scott |
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| | | Cancer Center of Kansas - Fort Scott |
| | | Shaker Dakhil, MD, FACP | |
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Independence |
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| | | Cancer Center of Kansas-Independence |
| | | Shaker Dakhil, MD, FACP | |
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Kingman |
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| | | Cancer Center of Kansas, PA - Kingman |
| | | Shaker Dakhil, MD, FACP | |
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Lawrence |
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| | | Lawrence Memorial Hospital |
| | | Shaker Dakhil, MD, FACP | |
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Liberal |
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| | | Southwest Medical Center |
| | | Shaker Dakhil, MD, FACP | |
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Newton |
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| | | Cancer Center of Kansas, PA - Newton |
| | | Shaker Dakhil, MD, FACP | |
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Parsons |
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| | | Cancer Center of Kansas, PA - Parsons |
| | | Shaker Dakhil, MD, FACP | |
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Pratt |
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| | | Cancer Center of Kansas, PA - Pratt |
| | | Shaker Dakhil, MD, FACP | |
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Salina |
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| | | Cancer Center of Kansas, PA - Salina |
| | | Shaker Dakhil, MD, FACP | |
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Wellington |
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| | | Cancer Center of Kansas, PA - Wellington |
| | | Shaker Dakhil, MD, FACP | |
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Wichita |
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| | | Associates in Womens Health, PA - North Review |
| | | Shaker Dakhil, MD, FACP | |
| | | Cancer Center of Kansas, PA - Wichita |
| | | Shaker Dakhil, MD, FACP | |
| | | Cancer Center of Kansas, PA - Medical Arts Tower |
| | | Shaker Dakhil, MD, FACP | |
| | | CCOP - Wichita |
| | | Shaker Dakhil, MD, FACP | |
| | | Via Christi Cancer Center at Via Christi Regional Medical Center |
| | | Shaker Dakhil, MD, FACP | |
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Winfield |
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| | | Cancer Center of Kansas, PA - Winfield |
| | | Shaker Dakhil, MD, FACP | |
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| Minnesota |
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Fridley |
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| | | | Mercy and Unity Cancer Center at Unity Hospital |
| | | Patrick Flynn, MD | |
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Maplewood |
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| | | Minnesota Oncology Hematology, PA - Maplewood |
| | | Patrick Flynn, MD | |
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Rochester |
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| | | Mayo Clinic Cancer Center |
| | | Clinical Trials Office - All Mayo Clinic Locations | |
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Shakopee |
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| | | St. Francis Cancer Center at St. Francis Medical Center |
| | | Patrick Flynn, MD | |
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Woodbury |
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| | | Minnesota Oncology Hematology, PA - Woodbury |
| | | Patrick Flynn, MD | |
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| Missouri |
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Cape Girardeau |
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| | | | Saint Francis Medical Center |
| | | Bethany Sleckman, MD | |
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Saint Louis |
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| | | CCOP - St. Louis-Cape Girardeau |
| | | Bethany Sleckman, MD | |
| | | David C. Pratt Cancer Center at St. John's Mercy |
| | | Clinical Trials Office - David C. Pratt Cancer Center at St. John's Mercy | |
| | | Midwest Hematology Oncology Group, Incorporated |
| | | Bethany Sleckman, MD | |
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| New York |
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Bronx |
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| | | | Our Lady of Mercy Medical Center Comprehensive Cancer Center |
| | | Peter Wiernik, MD | |
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Buffalo |
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| | | Roswell Park Cancer Institute |
| | | Clinical Trials Office - Roswell Park Cancer Institute | |
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| North Carolina |
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Charlotte |
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| | | | Blumenthal Cancer Center at Carolinas Medical Center |
| | | Clinical Trials Office - Blumenthal Cancer Center at Carolinas Medical Center | |
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Kinston |
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| | | Kinston Medical Specialists |
| | | Peter Watson, MD | |
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Winston-Salem |
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| | | Wake Forest University Comprehensive Cancer Center |
| | | Clinical Trials Office - Wake Forest University Comprehensive Cancer Center | |
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| Ohio |
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Cleveland |
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| | | | MetroHealth Cancer Care Center at MetroHealth Medical Center |
| | | Bruce Averbook, MD, FACS | |
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| Pennsylvania |
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Allentown |
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| | | | Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest |
| | | Eliot Friedman, MD | |
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Pittsburgh |
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| | | UPMC Cancer Centers |
| | | Clinical Trials Office - UPMC Cancer Centers | |
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Scranton |
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| | | Hematology and Oncology Associates of Northeastern Pennsylvania |
| | | Martin Hyzinski, MD | |
| | | Mercy Hospital Cancer Center - Scranton |
| | | Martin Hyzinski, MD | |
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| Wisconsin |
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La Crosse |
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| | | | Gundersen Lutheran Center for Cancer and Blood |
| | | Clinical Trials Office - Gundersen Lutheran Cancer Center | |
| | Email:
cancerctr@gundluth.org |
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Milwaukee |
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| | | Medical Consultants, Limited |
| | | Jonathan Treisman, MD | |
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| Registry Information | | | Official Title | | A Randomized Phase II Trial of Azacitidine with or without the Histone Deacetylase Inhibitor MS-275 for the Treatment of Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia (dysplastic type), and Acute Myeloid Leukemia with Multilineage Dysplasia | | | Trial Start Date | | 2006-08-18 | | | Trial Completion Date | | 2008-02-03 (estimated) | | | Registered in ClinicalTrials.gov | | NCT00313586 | | | Date Submitted to PDQ | | 2006-01-10 | | | Information Last Verified | | 2009-05-13 | | | NCI Grant/Contract Number | | CA21115 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. |
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