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

NCT00415857 | Terminated Phase 2 Results DMC

• 1 other identifier: 2006-0360
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leukemia

Keywords

Chronic Myelogenous Leukemia; Leukemia; Peptide Vaccine; PR1 Peptide; Imatinib; Gleevec; GM-CSF; Sargramostim; Leukine; Peginterferon alfa-2b; Peg-Intron

Outcome Measures

Primary Outcomes (1)

• Molecular Response Rate

  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.

  Baseline to 18 weeks, up to 6 months post final vaccination for overall study participation period.

Secondary Outcomes (1)

• Number of Participants With Immunologic Response

  Period of 18 weeks (i.e., one vaccination each on weeks 0, 3, 6, and 18).

Study Arms (2)

PR1 + Imatinib

EXPERIMENTAL

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); Drug: Imatinib; Drug: GM-CSF

PR1 + Imatinib + Interferon

EXPERIMENTAL

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); Drug: Peginterferon alfa-2b; Drug: Imatinib; Drug: GM-CSF

Interventions

Peptide Vaccine (PR1 Peptide) BIOLOGICAL

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.

Also known as: PR1 Vaccine

PR1 + Imatinib; PR1 + Imatinib + Interferon

Peginterferon alfa-2b DRUG

Subcutaneous injection of interferon 0.5 microg/kg with each PR1 vaccination.

Also known as: Peg-Intron

PR1 + Imatinib + Interferon

Imatinib DRUG

Continue receiving imatinib by mouth at the same dose received during the last 6 months.

Also known as: Gleevec

PR1 + Imatinib; PR1 + Imatinib + Interferon

GM-CSF DRUG

75 micrograms subcutaneously in the same area as the vaccine with every vaccination.

Also known as: Sargramostim, LeukineTM

PR1 + Imatinib; PR1 + Imatinib + Interferon

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients \>/= 18 years with Philadelphia chromosome (Ph)- or BCR/ABLpositive CML (as determined by cytogenetics, FISH, or PCR).
• Patients must have received imatinib therapy for at least 18 months and not have increased their dose of imatinib in the last 6 months.
• Patients must be in complete cytogenetic remission.
• 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
• 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.
• 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.
• Patients must be HLA-A2 positive at one allele
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status \</= 2.
• 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.
• Women of childbearing potential should practice effective methods of contraception.

You may not qualify if:

• Patients with a history or clinical evidence of autoimmune disorders
• Patients receiving immunosuppressive therapy including cyclosporine, or FK506 within 3 months of study entry
• 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)
• GM-CSF or interferon administration within 1 month of first PR1 injection
• Patients receiving any other investigational agents currently or within the past 4 weeks. Patients must have recovered from any adverse effects of investigational therapy.
• Patients who are pregnant or breast-feeding
• Patients with clinically significant heart disease (New York Heart Association (NYHA) Class III or IV)
• Patients with positive cANCA
• History of HIV positivity or AIDS
• Chloroma at time of study screening
• Prior vaccine therapy for Chronic myelogenous leukemia (CML)
• Known allergy to Montanide ISA-51 VG adjuvant

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• The Vaccine Company: collaborator

Study Sites (1)

UT MD . Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center website

MeSH Terms

Conditions

Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Protein Subunit Vaccines; peginterferon alfa-2b; Imatinib Mesylate; Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vaccines, Acellular; Vaccines, Subunit; Vaccines; Biological Products; Complex Mixtures; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Jorge Cortes M.D./Professor
• Organization: The University of Texas M. D. Anderson Cancer Center

eharrison@mdanderson.org

713/792-7305

Study Officials

• Jorge E. Cortes, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2006
• First Posted: December 25, 2006
• Study Start: December 1, 2006
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: August 21, 2018
• Results First Posted: April 30, 2014

Record last verified: 2018-07

Locations

US (1)