Vaccine Therapy in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from a peptide may help the body build an effective immune response to kill cancer cells. PURPOSE: This phase II trial is studying how well vaccine therapy works in treating patients with chronic phase chronic myelogenous leukemia.

Detailed Description
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OBJECTIVES: Determine the antileukemic effects of tumor-specific Breakpoint Cluster Region-Abelson Murine Leukemia(BCR-ABL) junction specific peptide vaccine, as measured by a decrease in circulating BCR-ABL transcripts by reverse-transcriptase polymerase chain reaction (RT-PCR), that persist for at least 3 months, in patients with chronic phase chronic myelogenous leukemia. Determine the percentage of patients treated with this vaccine who become RT-PCR-negative for BCR-ABL transcripts. Compare response in patients with B3A2 junctions vs B2A2 junctions when treated with this vaccine. Determine the immunologic response over 1 year in patients treated with this vaccine. Correlate response with specific HLA types in these patients. Determine the safety of this vaccine in these patients. OUTLINE: This is a pilot, multicenter study. Patients receive BCR-ABL junction-specific peptide vaccine subcutaneously in weeks 2, 4, 6, 8, and 11 and then once monthly for 10 months. BCR-ABL transcript levels are assessed by quantitative reverse-transcriptase polymerase chain reaction at baseline, weeks 2, 4, and 6, every 3 months during treatment, and then 2 weeks after completion of study treatment. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Official Title
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A Multi-Center Pilot Phase II Trial of a Synthetic Tumor-Specific Breakpoint Peptide Vaccine in Patients With Chronic Myeloid Leukemia (CML) and Minimal Residual Disease

Conditions
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Leukemia

Intervention / Treatment
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* Biological: bcr-abl peptide vaccine
* Genetic: reverse transcriptase-polymerase chain reaction


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of Philadelphia chromosome-positive or BCR-ABL-positive chronic phase chronic myelogenous leukemia (CML) In complete cytogenetic remission confirmed by 2 bone marrows ≥ 1 month apart Minimal residual disease Detectable BCR-ABL transcript levels obtained < 6 months apart AND ≤ 0.5-log lower than the lowest value obtained within the past 6 months PATIENT CHARACTERISTICS: Karnofsky performance status 80-100% Bilirubin < 2 times upper limit of normal (ULN) Creatinine < 1.5 times ULN ALT and AST < 2.5 times ULN PRIOR CONCURRENT THERAPY: Recovered from prior therapy No major surgery within the past 4 weeks No prior chemotherapy No prior immunosuppressive therapy No prior corticosteroids No prior stem cell transplantation No radiotherapy within the past 4 weeks No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bcr-abl peptide vaccine|Patients will be vaccinated 15 times over 12 months with a vaccine comprised of native and synthetic break-point cluster region-Abelson murine leukemia(BCR-ABL) specific peptides and the immunologic adjuvants, Montanide ISA 51-VG.|
|Genetic: reverse transcriptase-polymerase chain reaction|A baseline reverse transcriptase-polymerase chain reaction(RT-PCR) transcript level of BCR-ABL will be determined after enrollment on study. This baseline will be used to measure response to the vaccine. Patients will have 3 quantitative RT-PCR tests for BCR-ABL transcript levels performed on their peripheral blood in the first month after enrolling on study. Peripheral blood samples will be drawn at approximately 1-month prior (about day -30), 2 weeks prior (about day -14), and the day of the first vaccination (day 0). Samples will be analyzed at a central lab and the three values will be averaged to determine a baseline circulating transcript level. During this one-month period, a peripheral blood sample will be analyzed to determine whether patients have a B3A2 or B2A2 junction.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With One-log Decrease in Circulation Breakpoint Cluster Region-Abelson Murine Leukemia(BCR-ABL) Transcripts That Persists for at Least Three Months During the 1-year Treatment Period. | One-log decrease in circulating BCR-ABL transcripts (RT-PCR) that persists for at least three months during the 1-year treatment period. | Every 3 months for the duration of the 1-year treatment period. . | 
| Percentage of Patients Who Become RT-PCR-negative for BCR-ABL Transcripts |  | 12-24 Months | 
| Comparison of Response in Patients With B3A2 Junctions vs B2A2 Junctions |  | 12-24 Months | 
| Immunologic Response Over 1 Year |  | 12 months | 
| Correlation of Response With Specific HLA Types |  | 12-24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of a Vaccine Containing Native and Synthetic Chronic Myeloid Leukemia (CML) Peptides Over 1 Year Treatment. |  | Weeks 2, 4, 6, 9, and monthly thereafter up to 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia