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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 3
18 Years
N/A
Open (Enrolling)
Both
Leukemia

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Safety Issue:

No

Principal Investigator

Craig S. Rosenfeld, MD

Investigator Role:

Study Chair

Investigator Affiliation:

The Vaccine Company

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000510853

NCT ID:

NCT00454168

Start Date:

May 2005

Completion Date:

Related Keywords:

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

Name

Location

Mayo Clinic ScottsdaleScottsdale, Arizona  85259
University of Chicago Cancer Research CenterChicago, Illinois  60637
Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
Kansas Masonic Cancer Research Institute at the University of Kansas Medical CenterKansas City, Kansas  66160-7353
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390
Greenebaum Cancer Center at University of Maryland Medical CenterBaltimore, Maryland  21201
Jonsson Comprehensive Cancer Center at UCLALos Angeles, California  90095-1781
Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289
UPMC Cancer CentersPittsburgh, Pennsylvania  15232
Rush Cancer Institute at Rush University Medical CenterChicago, Illinois  60612
Vaccine CompanySouth San Francisco, California  94080
St. Francis Hospital Cancer Care ServicesIndianapolis, Indiana  46237
Cancer Care Centers of South Texas - SoutheastSan Antonio, Texas  78222