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

January 4, 2013 updated by: National Cancer Institute (NCI)

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

69

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Other: laboratory biomarker analysis
Correlative studies
Drug: Montanide ISA 51 VG
Given SC
Biological: sargramostim
Given SC
Other Names:
  • Leukine
  • Prokine
  • GM-CSF
Biological: PR1 leukemia peptide vaccine
Given SC
Other Names:
  • PR1 vac
  • proteinase 3 PR1 peptide
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.
Other: laboratory biomarker analysis
Correlative studies
Drug: Montanide ISA 51 VG
Given SC
Biological: sargramostim
Given SC
Other Names:
  • Leukine
  • Prokine
  • GM-CSF
Biological: PR1 leukemia peptide vaccine
Given SC
Other Names:
  • PR1 vac
  • proteinase 3 PR1 peptide
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.
Other: laboratory biomarker analysis
Correlative studies
Drug: Montanide ISA 51 VG
Given SC
Biological: sargramostim
Given SC
Other Names:
  • Leukine
  • Prokine
  • GM-CSF
Biological: PR1 leukemia peptide vaccine
Given SC
Other Names:
  • PR1 vac
  • proteinase 3 PR1 peptide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Up to 8 years
Ability of dose
Time Frame: Up to 8 years
Regression analyses will be performed.
Up to 8 years
T cell receptor (TCR) activity
Time Frame: Up to 8 years
Regression analyses will be performed.
Up to 8 years
Clinical response
Time Frame: Up to 8 years
Regression analyses will be performed.
Up to 8 years
Duration of first immune response (IR)
Time Frame: Up to 8 years
Will be assessed using logistic regression.
Up to 8 years
Survival time
Time Frame: Up to 8 years
Will be assessed using a Cox model or similar event time model
Up to 8 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Muzaffar Qazilbash, M.D. Anderson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 1999

Primary Completion (Actual)

December 1, 2007

Study Registration Dates

First Submitted

March 7, 2000

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

January 7, 2013

Last Update Submitted That Met QC Criteria

January 4, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-03086
  • DM 97-325

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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