Clinical trial NCT00454168: Vaccine Therapy and GM-CSF in Treating Patients With Acute Myeloid Leukemia in Remission
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Leukemia
Keywords: 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)
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-03-30
Enrollment: 244
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Overall survival
Secondary outcomes:
measure: Relapse-free survival
measure: Remission duration
measure: Immune response as measured by PR1-HLA-A2 tetramer assay
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center at UCLA
state: California
city: South San Francisco
country: United States
facility: Vaccine Company
state: California
city: Chicago
country: United States
facility: Rush Cancer Institute at Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: St. Francis Hospital Cancer Care Services
state: Indiana
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas - Southeast
state: Texas
Study officials:
affiliation: The Vaccine Company
name: Craig S. Rosenfeld, MD
role: STUDY_CHAIR
References: