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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2009 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00513578
First received: August 6, 2007
Last updated: January 3, 2014
Last verified: February 2009
  Purpose

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.


Condition Intervention Phase
Myelodysplastic Syndromes
Biological: PR1 leukemia peptide vaccine
Biological: incomplete Freund's adjuvant
Biological: sargramostim
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Conversion of non-immunologic responders to immunologic responders by administering 4 additional doses of vaccine [ Designated as safety issue: No ]
  • Clinical response as determined by modified IWG criteria [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: January 2007
Estimated Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
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.

  Eligibility

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

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
  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: NCT00513578

Locations
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
The Vaccine Company
Investigators
Study Chair: Craig S. Rosenfeld, MD The Vaccine Company
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00513578     History of Changes
Other Study ID Numbers: CDR0000558127, VACCINE-PR1-204
Study First Received: August 6, 2007
Last Updated: January 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
refractory anemia with excess blasts
refractory anemia with ringed sideroblasts
refractory anemia
refractory cytopenia with multilineage dysplasia
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Freund's Adjuvant
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014