Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Vaccine Therapy in Treating Patients With Chronic Myeloid Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Treatment Completed 18 and over NCI MSKCC-06051 NCT00267085

Objectives

Primary

1. Determine the anti-leukemic effects of chronic myelogenous leukemia (CML) breakpoint peptide vaccine, as measured by a one-log decrease in circulating BCR-ABL transcripts using reverse transcription-polymerase chain reaction (RT-PCR), in patients with CML.

Secondary

1. Determine the percentage of patients who become RT-PCR-negative for BCR-ABL transcripts when treated with this regimen.
2. Compare the responses in patients with B3A2 vs B2A2 junctions treated with this regimen.
3. Evaluate the immunologic responses at 1 year in patients treated with a vaccine containing native and synthetic CML peptides.
4. Correlate responses to peptide vaccine with immunologic responses in these patients.
5. Correlate responses to peptide vaccine with specific human leukocyte antigen types.
6. Determine the safety of a vaccine containing native and synthetic CML peptides in these patients.

Entry Criteria

Disease Characteristics:

• Diagnosis of chronic myelogenous leukemia (CML)
  • Philadelphia (Ph) chromosome-positive or BCR-ABL positive (as determined by cytogenetics, fluorescent in situ hybridization [FISH], or reverse transcription-polymerase chain reaction [RT-PCR])



• Must be in complete cytogenetic remission confirmed by 2 marrows ≥ 1 month apart
  • Not in complete molecular remission (i.e., still RT-PCR-positive)



• Currently receiving imatinib mesylate therapy for ≥ 12 months AND no change in dose within the past 6 months
  • No continuous interruption of imatinib mesylate therapy for ≥ 14 days OR for a total of 6 weeks within the past 6 months



• BCR-ABL transcript levels ≤ 0.5-log lower than the lowest value obtained within the past 6 months, with ≥ 2 values obtained during this period



• No history of accelerated phase CML or CML in blast crisis
  • Accelerated phase CML defined as 15-30% blasts or > 30% blasts plus promyelocytes in the peripheral blood or marrow, > 20% basophils, or platelet count < 100,000/mm³, unrelated to therapy
  • Cytogenetic abnormalities in addition to the Ph chromosome not considered a defining feature of accelerated phase CML

Prior/Concurrent Therapy:

• See Disease Characteristics
• At least 28 days since prior major surgery and recovered
• No prior stem cell transplantation
• At least 4 weeks since prior radiotherapy
• No concurrent immunosuppressive therapy, corticosteroids, chemotherapy, or other therapy for CML
• No other concurrent investigational agents
• Concurrent radiotherapy allowed provided it is not given for more than 2 weeks

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
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No autoimmune disorders or known primary immunodeficiency disease (i.e., severe combined immunodeficiency disorder, adenosine deaminase deficiency, or X-linked lymphoproliferative disorder)
• No clinically significant heart disease (New York Heart Association class III-IV heart disease)
• No other serious intercurrent illnesses, active uncontrolled infections requiring antibiotics, or active bleeding

Expected Enrollment

A total of 60 patients will be accrued for this study.

Outcomes

Anti-leukemic effects of treatment as measured by a one-log decrease in circulating BCR-ABL transcripts using reverse transcription-polymerase chain reaction (RT-PCR)

Percentage of patients who become RT-PCR-negative for BCR-ABL transcripts
Differences in responses in patients with B3A2 vs B2A2 junctions
Immunologic responses at 1 year
Correlation of responses to peptide vaccine with immunologic responses
Correlation of responses to peptide vaccine with specific human leukocyte antigen types
Safety and toxicity

Outline

This is a multicenter, pilot study. Patients are stratified according to peptide junctions (B3A2 vs B2A2).

Patients receive tumor-specific peptide vaccine (B3A2 patients receive CML-VAX B3; B2A2 patients receive CML-VAX B2) emulsified in incomplete Freund's adjuvant subcutaneously (SC) once on day 0 in weeks 0, 2, 4, 6, 9 and then once monthly on day 0 for 10 months. Patients also receive sargramostim (GM-CSF) SC on days -2 and 0 of each vaccination. Treatment continues in the absence of disease progression or unacceptable toxicity.

Periodically throughout study, patients undergo peripheral blood and bone marrow collection for evaluation of clinical and immunological response. Bone marrow cells are analyzed for cytogenetics. Blood is analyzed for BCR-ABL transcripts by reverse transcription-polymerase chain reaction and for immune response by T-cell proliferation, delayed-type hypersensitivity, and ELISPOT assay.

After completion of study treatment, patients are followed at 2 weeks.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Peter Maslak, MD, Principal investigator		Ph: 212-639-5518; 800-525-2225 Email: maslakp@mskcc.org

Registry Information
Official Title		A Pilot Phase II Trial of a Synthetic Tumor-Specific Breakpoint Peptide Vaccine in Patients with Chronic Myeloid Leukemia (CML) and Minimal Residual Disease
Trial Start Date		2006-08-23
Registered in ClinicalTrials.gov		NCT00267085
Date Submitted to PDQ		2006-09-01
Information Last Verified		2007-09-16
NCI Grant/Contract Number		CA08748, CA23766