Title
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
Phase
Phase 3Lead Sponsor
The Vaccine CompanyStudy Type
InterventionalStatus
Unknown statusIndication/Condition
LeukemiaIntervention/Treatment
pr1 peptide sargramostim ...Study Participants
244RATIONALE: 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.
Given subcutaneously
Given subcutaneously
Given subcutaneously
Patients receive PR1 leukemia peptide vaccine and sargramostim (GM-CSF) subcutaneously.
Patients receive placebo vaccine and GM-CSF subcutaneously.
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
