Proteinase 3 PR1 Peptide Mixed With Montanide ISA-51 VG Adjuvant and Administered With GM-CSF and PEG-INTRON(R)

This study has been terminated.
(Vaccine sponsor ceased operations.)
Sponsor:
Collaborator:
The Vaccine Company
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00415857
First received: December 22, 2006
Last updated: March 28, 2014
Last verified: March 2014
  Purpose

The goal of this clinical research study is to find out if using the PR1 peptide vaccine (PR1) without PEG-Intron® (interferon) or in combination with interferon can reduce or eliminate disease in patients who have CML that is in cytogenetic remission after treatment with imatinib mesylate, but who still have small amounts of disease able to be noticed (detected). Researchers want to see if giving low doses of interferon together with PR1 may make the vaccine more effective. The safety of treatment in this study will also be studied.


Condition Intervention Phase
Leukemia
Biological: Peptide Vaccine (PR1 Peptide)
Drug: Peginterferon alfa-2b
Drug: Imatinib
Drug: GM-CSF
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: Potential of Immunotherapy to Convert a Complete Cytogenetic Remission in Chronic Myelogenous Leukemia to a Molecular Complete Remission: Randomized Phase II Study of Proteinase 3 PR1 Peptide Mixed With Montanide ISA-51 VG Adjuvant and Administered With GM-CSF and Peginterferon Alfa-2b [PEG-INTRON(R), Schering Corporation]

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Molecular Response Rate [ Time Frame: Baseline to 18 weeks, up to 6 months post final vaccination for overall study participation period. ] [ Designated as safety issue: No ]
    Molecular response rate is number of respondents compared to total participants. Molecular Response is defined as a greater than a one-log reduction of Breakpoint Cluster Region-Abelson Murine Leukemia (BCR-ABL) transcript levels by quantitative polymerase chain reaction (PCR) from the baseline level at the time vaccination was initiated, or a disappearance of BCR-ABL transcripts, as measured by reverse transcription polymerase chain reaction (RT-PCR), occurring within 6 months from the last vaccination. Participants receive a series of 4 vaccinations administered at 3-week intervals and the fourth (final) vaccination administered 3 months after the third vaccination with blood draw to test PCR following every 3 months to test the level of leukemia in the blood and to see if disease is responding to the vaccine.


Secondary Outcome Measures:
  • Number of Participants With Immunologic Response [ Time Frame: Period of 18 weeks (i.e., one vaccination each on weeks 0, 3, 6, and 18). ] [ Designated as safety issue: No ]
    Immunologic Response (immune response) is defined as an increase of ≥ 0.5 PR1-HLA-A2 [human leukocyte antigen-A2 (HLA-A2)] tetramer cells / μl at the time of either the 3rd or 4th vaccination compared to the pre study absolute PR1-HLA-A2 tetramer cells / μl. Participants receive a total of 4 vaccinations over a period of 18 weeks (i.e., one vaccination each on weeks 0, 3, 6, and 18). Participants assessed after 3rd and 4th vaccination for immunologic response.


Enrollment: 5
Study Start Date: December 2006
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PR1 + Imatinib
PR1 peptide will be administered at a dose of 0.5 mg of PR1 on weeks 0, 3, 6 and 18 for a total of 4 doses. Continue receiving imatinib by mouth at the same dose received during the last 6 months. GM-CSF 75 micrograms subcutaneously in the same area as the vaccine with every vaccination.
Biological: Peptide Vaccine (PR1 Peptide)
PR1 peptide will be administered at a dose of 0.5 mg of PR1 on weeks 0, 3, 6 and 18 for a total of 4 doses.
Other Name: PR1 Vaccine
Drug: Imatinib
Continue receiving imatinib by mouth at the same dose received during the last 6 months.
Other Name: Gleevec
Drug: GM-CSF
75 micrograms subcutaneously in the same area as the vaccine with every vaccination.
Other Names:
  • Sargramostim
  • LeukineTM
Experimental: PR1 + Imatinib + Interferon
PR1 peptide will be administered at a dose of 0.5 mg of PR1 on weeks 0, 3, 6 and 18 for a total of 4 doses. Subcutaneous injection of interferon 0.5 microg/kg with each PR1 vaccination. GM-CSF 75 micrograms subcutaneously in the same area as the vaccine with every vaccination.
Biological: Peptide Vaccine (PR1 Peptide)
PR1 peptide will be administered at a dose of 0.5 mg of PR1 on weeks 0, 3, 6 and 18 for a total of 4 doses.
Other Name: PR1 Vaccine
Drug: Peginterferon alfa-2b
Subcutaneous injection of interferon 0.5 microg/kg with each PR1 vaccination.
Other Name: Peg-Intron
Drug: Imatinib
Continue receiving imatinib by mouth at the same dose received during the last 6 months.
Other Name: Gleevec
Drug: GM-CSF
75 micrograms subcutaneously in the same area as the vaccine with every vaccination.
Other Names:
  • Sargramostim
  • LeukineTM

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients >/= 18 years with Philadelphia chromosome (Ph)- or BCR/ABLpositive CML (as determined by cytogenetics, FISH, or PCR).
  2. Patients must have received imatinib therapy for at least 18 months and not have increased their dose of imatinib in the last 6 months.
  3. Patients must be in complete cytogenetic remission.
  4. Patients must have detectable BCR-ABL transcript levels meeting at least one of the following criteria: 1) Patient has never achieved a major molecular response (i.e., never reached levels <0.05%), and transcript levels have shown in at least two consecutive measures separated by at least 1 month to have increased by any value, or
  5. continued from above: 2) Achieved a major molecular response that has been lost with an increase in transcript levels by at least 1-log over two consecutive analyses separated by at least 1 month, or 3) BCR-ABL transcript levels have reached a plateau defined as a ratio that is not more than 0.25-log (one fourth of a log) lower than the lowest value obtained in the last at least 6 months, with at least 2 values obtained during this period.
  6. Patients must not have had a continuous interruption of imatinib therapy of greater than 14 days or any interruptions totaling 6 weeks within the 6 months prior to enrollment.
  7. Patients must be HLA-A2 positive at one allele
  8. Patients must give informed consent and sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital.
  9. Eastern Cooperative Oncology Group (ECOG) performance status </= 2.
  10. Adequate organ function defined as: bilirubin <2 times upper limit of normal (ULN), creatinine <1.5 times ULN, and serum glutamate pyruvate transaminase (sGPT) <2.5 times ULN.
  11. Women of childbearing potential should practice effective methods of contraception.

Exclusion Criteria:

  1. Patients with a history or clinical evidence of autoimmune disorders
  2. Patients receiving immunosuppressive therapy including cyclosporine, or FK506 within 3 months of study entry
  3. Chronic use (> 2 weeks) of greater than physiologic doses of corticosteroid agent (dose equivalent to > 10 mg/day of prednisone) within 28 days of the first day of study drug treatment (topical and inhaled corticosteroids are permitted)
  4. GM-CSF or interferon administration within 1 month of first PR1 injection
  5. Patients receiving any other investigational agents currently or within the past 4 weeks. Patients must have recovered from any adverse effects of investigational therapy.
  6. Patients who are pregnant or breast-feeding
  7. Patients with clinically significant heart disease (New York Heart Association (NYHA) Class III or IV)
  8. Patients with positive cANCA
  9. History of HIV positivity or AIDS
  10. Chloroma at time of study screening
  11. Prior vaccine therapy for Chronic myelogenous leukemia (CML)
  12. Known allergy to Montanide ISA-51 VG adjuvant
  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: NCT00415857

Locations
United States, Texas
UT MD . Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
The Vaccine Company
Investigators
Principal Investigator: Jorge E. Cortes, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00415857     History of Changes
Other Study ID Numbers: 2006-0360
Study First Received: December 22, 2006
Results First Received: March 28, 2014
Last Updated: March 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Chronic Myelogenous Leukemia
Leukemia
Peptide Vaccine
PR1 Peptide
Imatinib
Gleevec
GM-CSF
Sargramostim
Leukine
Peginterferon alfa-2b
Peg-Intron

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib
Peginterferon alfa-2b
Interferon-alpha
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2014