Vaccine Therapy in Treating Patients With Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia (CML0206)

Gruppo Italiano Malattie EMatologiche dell'Adulto

Status and phase: Completed; Phase 2

Conditions: Leukemia

Treatments: Biological: sargramostim; Biological: bcr-abl p210-b3a2 breakpoint-derived multipeptide vaccine

Study type: Interventional

Funder types: Other

Identifiers

NCT00466726

2006-006189-40 (EudraCT Number)

CML 0206

Details and patient eligibility

About

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill cancer cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving booster vaccinations may make a stronger immune response and prevent or delay the recurrence of cancer.

PURPOSE: This phase II trial is studying how well vaccine therapy works in treating patients with Philadelphia chromosome-positive chronic myelogenous leukemia.

Full description

OBJECTIVES:

Primary

• Determine the activity of bcr-abl p210-b3a2 breakpoint-derived pentapeptide vaccine (CMLVAX100), in terms of peripheral blood bcr-abl/abl ratio reduction, in patients with Philadelphia chromosome-positive chronic myelogenous leukemia.

Secondary

• Determine the reduction of molecular residual disease at 3 months in patients treated with this vaccine.
• Determine the reduction of molecular residual disease at 12 months in patients treated with maintenance boosts of this vaccine.
• Determine the rate of complete molecular response at any time after vaccination.
• Determine in vivo and in vitro peptide-specific immune response induced by the vaccine.

OUTLINE: This is a prospective, nonrandomized, open-label, multicenter study.

Patients receive sargramostim (GM-CSF) subcutaneously (SC) on days 1 and 2 and bcr-abl p210-b3a2 breakpoint-derived pentapeptide vaccine (CMLVAX100) SC on day 2. Treatment repeats every 2 weeks for 6 courses. Patients then receive CMLVAX100 SC once monthly for 3 months and then once every 3 months for 6 months (for a total of 1 year). Patients may receive additional CMLVAX100 SC every 6 months for at least 3 years. Treatment continues in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 69 patients will be accrued for this study.

Enrollment: 57 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of chronic myelogenous leukemia (CML) meeting the following criteria:

  • Philadelphia chromosome positive disease
  • b3a2 breakpoint mutation

• Prior treatment with conventional imatinib mesylate for ≥ 18 months required

  • Complete cytogenetic response documented on ≥ 2 different examinations

    • Persistence of molecularly detectable residual disease (any level of bcr-abl transcript)

  • Patients continue to receive imatinib mesylate at the same dose (conventional treatment) during study treatment

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Creatinine ≤ 1.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No severe active infection or other serious medical illness that would preclude study completion
• No known immunodeficiency
• No autoimmune disorders

PRIOR CONCURRENT THERAPY:

• No concurrent immunosuppression or systemic immunosuppressive medication
• No concurrent dose escalation of imatinib mesylate
• No other concurrent investigational products

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)