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

Sponsor

The Vaccine Company (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00454168

Collaborator

(none)

244

Enrollment

Locations

Arms

16.3

Patients Per Site

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: PR1 leukemia peptide vaccine Biological: sargramostim Other: placebo	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

244 participants

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2005

Anticipated Primary Completion Date :

Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive PR1 leukemia peptide vaccine and sargramostim (GM-CSF) subcutaneously.	Biological: PR1 leukemia peptide vaccine Given subcutaneously Biological: sargramostim Given subcutaneously
Active Comparator: Arm II Patients receive placebo vaccine and GM-CSF subcutaneously.	Biological: sargramostim Given subcutaneously Other: placebo Given subcutaneously

Arm

Intervention/Treatment

Experimental: Arm I

Patients receive PR1 leukemia peptide vaccine and sargramostim (GM-CSF) subcutaneously.

Biological: PR1 leukemia peptide vaccine

Given subcutaneously

Biological: sargramostim

Given subcutaneously

Active Comparator: Arm II

Patients receive placebo vaccine and GM-CSF subcutaneously.

Biological: sargramostim

Given subcutaneously

Other: placebo

Given subcutaneously

Outcome Measures

Primary Outcome Measures

Overall survival []

Secondary Outcome Measures

Relapse-free survival []
Remission duration []
Immune response as measured by PR1-HLA-A2 tetramer assay []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781
3	Vaccine Company	South San Francisco	California	United States	94080
4	Rush Cancer Institute at Rush University Medical Center	Chicago	Illinois	United States	60612
5	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
6	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202-5289
7	St. Francis Hospital Cancer Care Services	Indianapolis	Indiana	United States	46237
8	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
9	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
10	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
11	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
12	UPMC Cancer Centers	Pittsburgh	Pennsylvania	United States	15232
13	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
14	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390
15	Cancer Care Centers of South Texas - Southeast	San Antonio	Texas	United States	78222