Vaccine Therapy and GM-CSF in Treating Patients With Myeloid Cancer

Condition(s) targeted: Leukemia; Myelodysplastic Syndromes

Intervention: PR1 leukemia peptide vaccine (Biological); WT1 126-134 peptide vaccine (Biological); incomplete Freund's adjuvant (Biological); sargramostim (Biological)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)

Official(s) and/or principal investigator(s):
Quan Le, PhD, Principal Investigator, Affiliation: National Heart, Lung, and Blood Institute (NHLBI)

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, may increase the number of immune cells 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 the side effects and how well giving vaccine therapy together with GM-CSF works in treating patients with myeloid cancer.

Official title: Efficacy of WT1 and PR1 Peptide Vaccination for Patients With Low Risk Myeloid Malignancies

Study design: Treatment, Non-Randomized, Active Control

Primary outcome: Immune response as assessed by tetramer and intracellular staining for interferon-gamma production at baseline, during vaccination, and after completion of study therapy

Secondary outcome:

Reduction in bone marrow blast cells

Changes in blood counts

Transfusion dependence

Time to disease progression

Survival

Detailed description: OBJECTIVES:

Primary

- Evaluate the efficacy and toxicity associated with 6 doses of a combination of

WT1: 126-134 and PR1: 169-177 peptide vaccines in incomplete Freund's adjuvant administered concurrently with sargramostim (GM-CSF) in selected patients with myeloid malignancies (i. e., MDS, AML, or CML).

Secondary

- Clinically evaluate disease response using hematological measurements (i. e., reduction

in marrow blast cells, changes in blood counts), transfusion dependence, time to disease progression, and survival.

OUTLINE: Patients receive WT1: 126-134 and PR1: 169-177 peptide vaccines emulsified in incomplete Freund's adjuvant subcutaneously (SC) administered concurrently with sargramostim (GM-CSF) SC once every 2 weeks. In order to monitor the local effects of each vaccine, injections are administered to separate sites that are rotated every 2 weeks. Treatment continues for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with immunological response to one or both peptide vaccines will have the option of receiving an additional 6 boosters of the peptide vaccines at 3 monthly intervals.

After completion of study therapy, patients are followed at weeks 12 and 16.

Minimum age: 18 Years. Maximum age: 85 Years. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Diagnosis of 1 of the following:

- Myelodysplastic syndromes (MDS), including 1 of the following FAB histologic

subtypes:

- Refractory anemia

- Refractory anemia with ringed sideroblasts (low-risk disease)

- AND meets the following criteria:

- No hypoplastic MDS

- No relapsed MDS after hematopoietic stem cell transplantation

- Acute myeloid leukemia (AML) meeting the following criteria:

- In complete remission within 5 years of prior treatment

- Less than 5% marrow blasts

- No relapsed AML

- Chronic myelogenous leukemia (CML) meeting the following criteria:

- In chronic phase

- No relapsed CML following hematopoietic stem cell transplantation

- No CML in accelerated phase or blast crisis

- Meets 1 of the following criteria:

- Not suitable for stem cell transplantation due to age over 60 years OR a

fully-matched donor is not available

- Made an informed decision not to undergo the transplantation procedure

- At least 6 months-3 years since prior allogeneic stem cell transplantation AND

demonstrates the following clinical features:

- 100% donor engraftment

- Less than 5% blasts in marrow

- Normal marrow cellularity

- No hypocellular bone marrow (i. e., < 20%)

- HLA-A0201 positive at one allele

- No history of Wegener's granulomatosis or vasculitis

PATIENT CHARACTERISTICS:

- See Disease Characteristics

- Predicted survival ≥ 28 days

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Hemoglobin ≥ 9 g/dL

- Absolute neutrophil count ≥ 1,000/mm³

- Platelet count ≥ 75,000/mm³

- No serologic antibody against proteinase-3 (i. e., ANCA positive)

- No prior allergic reaction to incomplete Freund's adjuvant

- HIV-negative

- No comorbidity of such severity that it would preclude the patient's ability to

tolerate protocol therapy

PRIOR CONCURRENT THERAPY:

- More than 14 days since prior systemic corticosteroids

- No concurrent enrollment in another drug or vaccine clinical study

- Concurrent nonlymphoablative chemotherapeutic agents (e. g., tyrosine kinase inhibitors

or hydroxyurea) allowed for control of disease burden at the discretion of the principal investigator

NIH - Warren Grant Magnuson Clinical Center, Bethesda, Maryland 20892-1182, United States; Recruiting
Clinical Trials Office - NIH - Warren Grant Magnuson Clinical, Phone: 800-411-1222

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: June 2007
Last updated: February 6, 2009