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
  Purpose

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


Condition Intervention Phase
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
Drug: Montanide ISA 51 VG
Biological: sargramostim
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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


Estimated Enrollment: 69
Study Start Date: December 1999
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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 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.
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 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.
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004918

Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Muzaffar Qazilbash M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00004918     History of Changes
Other Study ID Numbers: NCI-2012-03086, DM 97-325
Study First Received: March 7, 2000
Last Updated: January 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Anemia
Anemia, Refractory
Anemia, Refractory, with Excess of Blasts
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Myelodysplastic Syndromes
Preleukemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Precancerous Conditions
Freund's Adjuvant
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014