Vaccine Therapy Plus Immune Adjuvant in Treating Patients With Chronic Myeloid Leukemia, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00004918
First received: March 7, 2000
Last updated: January 4, 2013
Last verified: January 2013

March 7, 2000
January 4, 2013
December 1999
December 2007   (final data collection date for primary outcome measure)
  • Adverse event DTOX (death or autoimmune toxicity or vascular toxicity at any time) assessed using Common Toxicity Criteria (CTC) version 2.0 [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
  • Ability of dose [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    Regression analyses will be performed.
  • T cell receptor (TCR) activity [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    Regression analyses will be performed.
  • Clinical response [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    Regression analyses will be performed.
  • Duration of first immune response (IR) [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    Will be assessed using logistic regression.
  • Survival time [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    Will be assessed using a Cox model or similar event time model
Not Provided
Complete list of historical versions of study NCT00004918 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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Vaccine Therapy Plus Immune Adjuvant in Treating Patients With Chronic Myeloid Leukemia, Acute Myeloid Leukemia, or Myelodysplastic Syndrome
A Phase I/II Study of PR1 (NSC 698102) Human Leukemia Peptide Vaccine With Montanide ISA 51 (NSC 675756) or Montanide ISA 51 VG (NSC 737063) Adjuvant

Vaccines made from peptides that are found on leukemia cells may make the body build an immune response and kill cancer cells. Combining vaccine therapy with the immune adjuvant Montanide ISA-51 may be a more effective treatment for chronic myeloid leukemia, acute myeloid leukemia, or myelodysplastic syndrome. This phase I/II trial is studying the side effects and best dose of vaccine therapy when given with Montanide ISA-51 and to see how well they work in treating patients with chronic myeloid leukemia, acute myeloid leukemia, or myelodysplastic syndrome

PRIMARY OBJECTIVES:

I. To evaluate both toxicity and immune response efficacy of PR1 peptide (PR1 leukemia peptide vaccine) administered subcutaneously.

SECONDARY OBJECTIVES:

I. To evaluate possible clinical efficacy of PR1 peptide vaccine preparation with Montanide ISA 51 or Montanide ISA 51 VG adjuvant, in high-risk HLA-A2 positive patients with myeloid leukemias.

OUTLINE: This is a phase I dose-escalation study of PR1 leukemia peptide vaccine, followed by a phase II randomized study.

Patients receive PR1 leukemia peptide vaccine with Montanide ISA-51 (ISA-51) subcutaneously (SC) once every 3 weeks for 18 weeks, for a total of 6 vaccinations. Patients also receive sargramostim (GM-CSF) SC with each vaccination.

Cohorts of 3 patients receive escalating doses of PR1 leukemia peptide vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 patients experience dose-limiting toxicity.

Additional patients are accrued to the phase II portion of the study and are randomized to receive one of three dose levels of PR1 leukemia peptide vaccine with ISA-51. Patients in each of the 3 arms receive treatment as in the phase I portion of the study.

Patients achieving a clinical response and/or clinical response to the vaccine whose disease progresses within 6-12 months after the first set of vaccinations may receive additional vaccine as before.

Patients achieving a clinical response or immune reaction to the vaccine are followed at least monthly until death or until the clinical response and/or immune reaction is lost.

PROJECTED ACCRUAL: A total of 3-9 patients will be accrued for the phase I dose escalation portion of this study. A maximum of 60 patients (20 per arm) will be accrued for the phase II randomized portion of this study.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Accelerated Phase Chronic Myelogenous Leukemia
  • Adult Acute Myeloid Leukemia in Remission
  • Chronic Phase Chronic Myelogenous Leukemia
  • Previously Treated Myelodysplastic Syndromes
  • Refractory Anemia With Excess Blasts
  • Refractory Anemia With Excess Blasts in Transformation
  • Relapsing Chronic Myelogenous Leukemia
  • Biological: PR1 leukemia peptide vaccine
    Given SC
    Other Names:
    • PR1 vac
    • proteinase 3 PR1 peptide
  • Drug: Montanide ISA 51 VG
    Given SC
  • Biological: sargramostim
    Given SC
    Other Names:
    • GM-CSF
    • Leukine
    • Prokine
  • Other: laboratory biomarker analysis
    Correlative studies
  • Experimental: Arm I (dose level 1 PR1 leukemia peptide vaccine)
    Patients receive dose level 1 of PR1 leukemia peptide vaccine with Montanide ISA-51 SC once every 3 weeks for 18 weeks, for a total of 6 vaccinations. Patients also receive GM-CSF SC with each vaccination.
    Interventions:
    • Biological: PR1 leukemia peptide vaccine
    • Drug: Montanide ISA 51 VG
    • Biological: sargramostim
    • Other: laboratory biomarker analysis
  • Experimental: Arm II (dose level 2 PR1 leukemia peptide vaccine)
    Patients receive dose level 2 of PR1 leukemia peptide vaccine with Montanide ISA-51 SC once every 3 weeks for 18 weeks, for a total of 6 vaccinations. Patients also receive GM-CSF SC with each vaccination.
    Interventions:
    • Biological: PR1 leukemia peptide vaccine
    • Drug: Montanide ISA 51 VG
    • Biological: sargramostim
    • Other: laboratory biomarker analysis
  • Experimental: Arm III (dose level 3 PR1 leukemia peptide vaccine)
    Patients receive dose level 3 of PR1 leukemia peptide vaccine with Montanide ISA-51 SC once every 3 weeks for 18 weeks, for a total of 6 vaccinations. Patients also receive GM-CSF SC with each vaccination.
    Interventions:
    • Biological: PR1 leukemia peptide vaccine
    • Drug: Montanide ISA 51 VG
    • Biological: sargramostim
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
69
Not Provided
December 2007   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must be HLA-A2 positive at one allele
  • Patients with CML in chronic phase or early accelerated phase, who are not eligible for BMT or interferon, or have failed standard therapy, or have relapsed after BMT
  • Patients with MDS (FAB subtypes RAEB, and RAEBt) or AML in second or subsequent remission, or AML with a smoldering presentation and who are not candidates for chemotherapy, and who are believed to have a life expectancy of at least 9 weeks
  • ECOG performance status < 3
  • Life expectancy is not severely limited by concomitant illness
  • Serum bilirubin < 3 mg/dl
  • Serum creatinine < 2 mg/dl
  • ALT < 3 x the upper limit of normal
  • No serologic antibody against proteinase 3
  • No known history of Wegener's granulomatosis or other vasculitis
  • FEV, FVC, and DLCO > 50% of predicted, and no symptomatic pulmonary disease
  • Not pregnant; all female patients will have a serum pregnancy test, and only those that test negative will be allowed on study
  • HIV negative
  • No known allergic reaction to Montanide ISA 51 or Montanide ISA 51 VG adjuvant
  • No active uncontrolled infection
  • Patient or representative able to understand the study and consent
  • Patient is not receiving steroids, cyclosporine, or FK-506 for at least 1 month prior to study entry and during study period
  • No concomitant use of interferon or chemotherapy during study period other than hydroxyurea to control cell counts
  • Patients who relapsed within one year of completing the initial vaccination could be retreated with up to 6 additional vaccinations if they remain eligible for treatment according to the original criteria
Both
19 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00004918
NCI-2012-03086, DM 97-325
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Muzaffar Qazilbash M.D. Anderson Cancer Center
National Cancer Institute (NCI)
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP