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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

Phase 2
18 Years
Open (Enrolling)
Myelodysplastic Syndromes

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Trial Information

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



- 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.


- 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.

Inclusion Criteria


Inclusion criteria:

- Diagnosis of myelodysplastic syndromes (MDS) and must meet all of the following

- 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)


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

- 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


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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

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

Safety Issue:


Principal Investigator

Craig S. Rosenfeld, MD

Investigator Role:

Study Chair

Investigator Affiliation:

The Vaccine Company


United States: Food and Drug Administration

Study ID:




Start Date:

January 2007

Completion Date:

Related Keywords:

  • Myelodysplastic Syndromes
  • refractory anemia with excess blasts
  • refractory anemia with ringed sideroblasts
  • refractory anemia
  • refractory cytopenia with multilineage dysplasia
  • de novo myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • Myelodysplastic Syndromes
  • Preleukemia



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