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

• ClinicalTrials.gov Identifier: NCT00454168
• Recruitment Status: Unknown
• First Posted: March 30, 2007
• Last Update Posted: January 6, 2014
• Sponsor: The Vaccine Company
• Information provided by: National Cancer Institute (NCI)

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 (Clinical Trial)
• Estimated 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 2005
• Estimated Primary Completion Date: April 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

Outcome Measures

Primary Outcome Measures :

1. Overall survival

Secondary Outcome Measures :

1. Relapse-free survival
2. Remission duration
3. Immune response as measured by PR1-HLA-A2 tetramer assay

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

United States, Arizona

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States, 85259-5499

United States, California

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, United States, 90095-1781

Vaccine Company

South San Francisco, California, United States, 94080

United States, Illinois

Rush Cancer Institute at Rush University Medical Center

Chicago, Illinois, United States, 60612

University of Chicago Cancer Research Center

Chicago, Illinois, United States, 60637-1470

United States, Indiana

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States, 46202-5289

St. Francis Hospital Cancer Care Services

Indianapolis, Indiana, United States, 46237

United States, Kansas

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Kansas City, Kansas, United States, 66160-7357

United States, Maryland

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States, 21201

United States, North Carolina

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States, 27599-7295

United States, Ohio

Case Comprehensive Cancer Center

Cleveland, Ohio, United States, 44106-5065

United States, Pennsylvania

UPMC Cancer Centers

Pittsburgh, Pennsylvania, United States, 15232

United States, South Carolina

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States, 29425

United States, Texas

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States, 75390

Cancer Care Centers of South Texas - Southeast

San Antonio, Texas, United States, 78222

Sponsors and Collaborators

The Vaccine Company

Investigators

• Study Chair: Craig S. Rosenfeld, MD; The Vaccine Company

More Information

• Responsible Party: Regulatory Protocol Associate, Vaccine Company
• ClinicalTrials.gov Identifier: NCT00454168
• Other Study ID Numbers: CDR0000510853; VACCINE-PR1-104; UCCRC-14613B
• First Posted: March 30, 2007
• Last Update Posted: January 6, 2014
• Last Verified: February 2009

Keywords provided by National Cancer Institute (NCI):

adult acute minimally differentiated myeloid leukemia (M0); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myeloid leukemia in remission; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myelomonocytic leukemia (M4); adult acute promyelocytic leukemia (M3); secondary acute myeloid leukemia; adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); adult acute megakaryoblastic leukemia (M7)

Additional relevant MeSH terms:

Leukemia; Neoplasms by Histologic Type; Neoplasms; Vaccines; Sargramostim; Immunologic Factors; Physiological Effects of Drugs