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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00454168
• Other study ID #: CDR0000510853
• Secondary ID: VACCINE-PR1-104U
• Status: Active, not recruiting
• Phase: Phase 3
• First received: March 27, 2007
• Last updated: January 3, 2014
• Start date: May 2005

Study information

• Verified date: February 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 244
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Biological:
• PR1 leukemia peptide vaccine
Given subcutaneously
• sargramostim
Given subcutaneously

Other:
• placebo
Given subcutaneously

Locations

Country	Name	City	State
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Rush Cancer Institute at Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	St. Francis Hospital Cancer Care Services	Indianapolis	Indiana
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California
United States	UPMC Cancer Centers	Pittsburgh	Pennsylvania
United States	Cancer Care Centers of South Texas - Southeast	San Antonio	Texas
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Vaccine Company	South San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
The Vaccine Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival			No
Secondary	Relapse-free survival			No
Secondary	Remission duration			No
Secondary	Immune response as measured by PR1-HLA-A2 tetramer assay			No