Vaccine Therapy and GM-CSF in Treating Patients With Low-Risk or Intermediate-Risk Myelodysplastic Syndrome

January 3, 2014 updated by: The Vaccine Company

Phase 2 Study of Proteinase 3 PR1 Peptide Mixed With Montanide ISA 51 VG Adjuvant and Administered With GM-CSF in Low Risk and Intermediate-1 MDS

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill cancer cells. Colony-stimulating factors, such as GM-CSF, increase the number of white blood cells and platelets found in bone marrow or peripheral blood. Giving vaccine therapy together with GM-CSF may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving vaccine therapy together with GM-CSF works in treating patients with low-risk or intermediate-risk myelodysplastic syndrome.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To determine the immunologic response, using a PR1-HLA-A2 tetramer assay, to 4 subcutaneous injections of PR1 leukemia peptide vaccine formulated in incomplete Freund's adjuvant (IFA) followed by sargramostim (GM-CSF) in patients with low- and intermediate-1-risk myelodysplastic syndromes.

Secondary

  • To determine if non-immunologic responders to 4 subcutaneous injections of PR1 leukemia peptide vaccine formulated in IFA followed by GM-CSF can be converted to immunologic responders by administering 4 additional doses of this treatment.
  • To determine the clinical response to 4 or 8 subcutaneous injections of this vaccine.

OUTLINE: This is a multicenter study.

Patients will receive proteinase PR1 leukemia peptide vaccine (TVC-PR1) conjugated with incomplete Freund's adjuvant administered subcutaneously with sargramostim (GM-CSF). Patients will receive a series of four vaccinations at 3-week intervals. Non-immunologic responders after 4 doses of vaccine are eligible to receive 4 additional doses of TVC-PR1 vaccine with the same dose and same dosing intervals. Patients who mount an immunologic response after 4 doses will not receive additional doses of TVC-PR1 vaccine.

After completion of study therapy, patients are followed monthly for up to 6 months.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

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, 77030-4009
        • M. D. Anderson Cancer Center at University of Texas

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

Inclusion criteria:

  • Diagnosis of myelodysplastic syndromes (MDS) and must meet all of the following criteria:

    • FAB class refractory anemia (RA), RA with excess blasts (RAEB), or RA with ringed sideroblasts (RARS)
    • WHO Classification RA, RARS, refractory cytopenia with multilineage dysplasia (RCMD), RCMD with ringed sideroblasts, or RAEB-1
    • Less than 20% blasts on marrow aspirate
    • IPSS risks groups intermediate-1- OR transfusion dependent low-risk
    • Patients with de novo or therapy-related MDS eligible
  • HLA-A2 positive at one allele

Exclusion criteria:

  • RAEB in transformation or RAEB-2
  • Chloroma
  • Marrow blasts on aspirate ≥ 20%
  • Blood blasts > 1%
  • Inaspirable bone marrow
  • History or current myelosclerosis occupying > 30% of marrow space
  • History of acute myeloid leukemia
  • Other causes of cytopenia not related to MDS (i.e., gastrointestinal blood loss)

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • ECOG performance status 0 or 1
  • Women of childbearing potential must have a negative serum pregnancy test within 30 days of starting study drug
  • Male or female of child-bearing potential must agree to use adequate contraceptive methods
  • Serum bilirubin < 2 mg/mL
  • Creatinine ≤ 1.5 mg/mL
  • ALT < 2 times upper normal limit
  • Antineutrophil cytoplasmic antibody (cANCA) negative

Exclusion criteria:

  • Pregnant or lactating
  • Iron absence on marrow examination or transferrin saturation < 20% and serum ferritin < 50ng/mL
  • B12 deficiency
  • Folate deficiency
  • History of immune-related hematological disorder (i.e., idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia)
  • Life expectancy severely limited by diseases other than MDS
  • Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for ≥ 5 years
  • Known allergy to incomplete Freund's adjuvant
  • Hypercalcemia

  • Progressive viral or bacterial infection

    • All infections must be resolved and the patient has remained afebrile for seven days without antibiotics
  • Cardiac disease of symptomatic nature or cardiac ejection fraction < 40%
  • History of Wegener granulomatosis or vasculitis
  • Symptomatic pulmonary disease or FEV_1, FVC, and DLCO ≤ 50% predicted
  • History of HIV positivity or AIDS
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form or that will place the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret the data

PRIOR CONCURRENT THERAPY:

Exclusion criteria:

  • Has received specific therapy for MDS within the past 4 weeks
  • Prior allogeneic or syngeneic transplant
  • Prior solid organ transplant

  • Chronic use (> 2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to > 10 mg/day of prednisone) within 30 days of the first day of study drug treatment

    • Topical and inhaled corticosteroids are permitted
  • Experimental therapy, cyclosporine, antithymocyte globulin, or tacrolimus within 3 months of study entry
  • Treatment with androgenic hormones, danazol, colony-stimulating factors, erythropoietin, thalidomide, arsenic trioxide or other agents used to treat MDS within four weeks of the first day of study treatment
  • Prior vaccine therapy for MDS

  • Prohibited medications during study, including any of the following:

    • Systemic steroids except as required for transfusion reactions
    • Chemotherapy or other investigational drugs
    • Sargramostim (GM-CSF) (except as part of study regimen)
    • Filgrastim (G-CSF)
    • Interleukin-11

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
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Immunologic response after four injections of vaccine formulation as determined by an increase in the absolute PR1-HLA-A2 tetramer count by at least 0.5/μl

Secondary Outcome Measures

Outcome Measure
Conversion of non-immunologic responders to immunologic responders by administering 4 additional doses of vaccine
Clinical response as determined by modified IWG criteria

Collaborators and Investigators

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

Sponsor

The Vaccine Company

Investigators

  • Study Chair: Craig S. Rosenfeld, MD, The Vaccine Company

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

January 1, 2007

Primary Completion (Anticipated)

January 1, 2009

Study Registration Dates

First Submitted

August 6, 2007

First Submitted That Met QC Criteria

August 6, 2007

First Posted (Estimate)

August 8, 2007

Study Record Updates

Last Update Posted (Estimate)

January 6, 2014

Last Update Submitted That Met QC Criteria

January 3, 2014

Last Verified

February 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000558127
  • VACCINE-PR1-204

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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