Vaccine Therapy and GM-CSF in Treating Patients With Acute Myeloid Leukemia in Remission

A Phase 3, Randomized, Double-Blind, Multicenter Study of Proteinase 3 PR1 Peptide Mixed With Montanide ISA-51 VG Adjuvant and Administered With GM-CSF in Elderly Patients With AML in First Complete Remission or Adults in Second Complete Remission: A Pivotal Study

RATIONALE: Vaccines made from a peptide may help the body build an effective immune response to kill cancer cells. Colony-stimulating factors, such as GM-CSF, increase the number of white blood cells and platelets found in bone marrow or peripheral blood. Giving vaccine therapy together with GM-CSF may be an effective treatment for acute myeloid leukemia. It is not yet known whether giving vaccine therapy together with GM-CSF is more effective than giving placebo together with GM-CSF in treating acute myeloid leukemia.

PURPOSE: This randomized phase III trial is studying vaccine therapy and GM-CSF to see how well they work compared with a placebo and GM-CSF in treating patients with acute myeloid leukemia in remission.

OBJECTIVES:

Primary

• Compare improvement of overall survival of patients with acute myeloid leukemia treated with PR1 leukemia peptide vaccine and sargramostim (GM-CSF) vs placebo vaccine and GM-CSF.

Secondary

• Compare improvement of relapse-free survival of patients treated with these regimens.
• Compare remission duration in patients treated with these regimens.
• Compare immune response, as measured by PR1-HLA-A2 tetramer assay, in patients treated with these regimens.

OUTLINE: This is a randomized, placebo-controlled, multicenter study. Patients are stratified according to age and complete remission (CR) (≥ 18 years of age and in second CR vs ≥ 55 years of age and in first CR), type of acute myeloid leukemia (de novo vs secondary), and cytogenetics (unfavorable vs favorable and intermediate). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive PR1 leukemia peptide vaccine and sargramostim (GM-CSF) subcutaneously (SC).
• Arm II: Patients receive placebo vaccine and GM-CSF SC.

PROJECTED ACCRUAL: A total of 244 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of acute myeloid leukemia (AML), defined by the presence of > 20% blasts in marrow or blood, including the following subtypes:

  • De novo AML, defined as AML with no clinical history of prior myelodysplastic syndromes (MDS) or myeloproliferative disorder (MPD) or exposure to potentially leukemogenic therapies or agents

  • Secondary AML, defined as the following:

    • AML secondary to prior existing MDS or MPD or development of AML secondary to proven leukemogenic exposure
    • History of fatigue, bleeding, or recurrent infections preceding diagnosis of AML by ≥ 1 month with confirmation of existing peripheral blood film that demonstrates morphologic dysplasia

• In first complete remission (CR) (patients ≥ 55 years of age) OR second CR (patients ≥ 18 years of age) within the past month

  • FAB stages M0-M2 and M4-M7 allowed if in first CR

    • No acute promyelocytic leukemia in first CR

  • FAB stages M0-M7 allowed if in second CR

  • Marrow blast count < 5% (≤ 200 nucleated cell count)

    • No blasts in blood

• HLA-A2 positive at 1 allele

• No extramedullary disease

• No Auer rods

• No active meningeal or CNS leukemia

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• Life expectancy must not be severely limited by other diseases

• Absolute neutrophil count > 1,000/mm^3

• Platelet count > 100,000/mm^3

• Bilirubin < 2 mg/mL

• ALT < 2 times upper limit of normal

• Creatinine ≤ 1.6 mg/mL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Antineutrophil cytoplasmic antibody negative

• No serious medical condition, laboratory abnormality, or psychiatric illness that would preclude study compliance or increase risk to patient

• No other malignancy within the past 5 years except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast

• No known allergy to incomplete Freund's adjuvant

• No hypercalcemia

• No progressive viral or bacterial infection

  • Must be afebrile for 7 days without antibiotics

• No symptomatic cardiac disease

• LVEF ≥ 40%

• No symptomatic pulmonary disease

• FEV_1, FVC, and DLCO ≥ 50% of predicated (without bronchodilator)

• No history of HIV positivity or AIDS

• No known hypersensitivity to sargramostim (GM-CSF), yeast-derived products, or any component of this product

• No history of Wegener's granulomatosis or vasculitis

PRIOR CONCURRENT THERAPY:

• Recovered from prior surgery and/or radiotherapy

• No prior allogeneic or syngeneic stem cell transplantation

• No prior solid organ transplantation

• No prior vaccine therapy for AML

• More than 28 days since prior chronic use (> 2 weeks) of corticosteroids > 10 mg/day (prednisone [or equivalent])

  • Concurrent topical or inhaled corticosteroids allowed

• More than 3 months since prior experimental therapy, cyclosporine, or tacrolimus

• No concurrent radiotherapy