Safety of Peptide Vaccination for Patients With Myelodysplastic Syndrome

NCT00270452 | Completed Phase 1

• 2 other identifiers: 06006206-H-0062
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test whether certain patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) can safely be vaccinated with two peptide vaccines derived from proteins called proteinase 3 (PR1) and Wilm's tumor-1 (WT1). These proteins are produced in large amounts by cells of MDS, AML and CML patients. The peptides are combined with an "adjuvant" called Montanide to make the vaccines, and the vaccines are given with GM-CSF (sargramostim). Both Montanide and sargramostim help the immune system respond to the vaccines. The vaccines then activate the immune system to make specialized cells that search out and kill the MDS, AML and CML cells containing the two proteins. Patients with MDS, AML or CML who are 18 years of age or older may be eligible for this study. Candidates are screened with a medical history and physical examination, blood tests, chest x-ray, and bone marrow aspirate and biopsy. For the bone marrow biopsy, the area of the hip is anesthetized and a special needle is used to draw marrow from the hipbone. Participants receive an injection (shot) of each peptide vaccine into deep tissue of the upper arm, upper leg, or the abdomen and two separate shots of sargramostim in the same area as the vaccine shots. Patients' vital signs (heart rate, breathing rate, temperature, blood pressure) are measured before and after they receive the vaccines and they are watched for 2 hours after the shots for possible side effects, such as chills, pain at the injection site, stomach upset, allergic reaction, low blood counts, and infection. Patients return to the clinic 1, 2, 3 and 4 weeks after receiving the vaccines for a brief physical evaluation and blood tests. A chest x-ray is also done at the 4-week visit. Patients may receive whole blood or platelet transfusions if needed to treat the MDS, growth factors (filgrastim, erythropoietin, or others) if needed, and medications to treat any infections that may develop.

Conditions

Myelodysplastic Syndrome (MDS)

Keywords

Myelodyplastic Syndrome (MDS); Wilm's tumor-1; Proteinase-3; Vaccine Therapy; Acute Myeloid Leukemia; Chronic Myeloid Leukemias; Myelodysplastic Syndrome; MDS

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety of and toxicity assoc. with a single dose of a comb. of PR1:169-177 and WT-1:126-134 peptide (in Montanide adjuvant) vaccination admin. concomitantly with GM-CSF (Sargramostim) in selected patients with myeloid malignancie...

Interventions

WT1 and PR1 Peptide Vaccine DRUG

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with FAB subtypes RA, RARS MDS (Low Risk)
• Diagnosed with AML and in complete remission within 5 years of treatment with less than 5 percent marrow blasts
• Diagnosed with CML In chronic phase
• Diagnosed with MDS, AML or CML and are between 6 months-3 years following allogeneic SCT who fulfill the following criteria:
• percent donor engraftment,
• less than 5 percent blasts in marrow
• normal marrow cellularity
• HLA-A0201 positive at one allele
• Ages 18 - 85 years old

You may not qualify if:

• Hypoplastic MDS
• Relapsed AML
• CML in accelerated phase or blast crisis
• Relapsed MDS, AML or CML following hematopoietic stem cell transplantation
• Hb less than 9 g/dl, neutrophil count less than 1 times 10(9)/1, and/ or platelet count less than 75 times 10(9)/1
• Hypocellular bone marrow
• History of Wegener's granulomatosis
• Serologic antibody against proteinase-3 (ANCA positive)
• Previous allergic reaction to montanide adjuvant
• Positive test for HIV
• Treatment with systemic corticosteroids within 14 days prior to study entry
• Co-morbidity of such severity that it would preclude the subject's ability to tolerate protocol therapy
• Predicted survival less than 28 days
• Pregnant or breast feeding (All female subjects must have a urine pregnancy test within 1 week prior to vaccine administration)
• Enrolled in another drug or vaccine clinical trial during the study period

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Estey EH. Prognosis and therapy of secondary myelodysplastic syndromes. Haematologica. 1998 Jun;83(6):543-9.

  PMID: 9676028 BACKGROUND

• Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982 Jun;51(2):189-99.

  PMID: 6952920 BACKGROUND

• Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002 Oct 1;100(7):2292-302. doi: 10.1182/blood-2002-04-1199.

  PMID: 12239137 BACKGROUND

• Rezvani K, Yong AS, Mielke S, Savani BN, Musse L, Superata J, Jafarpour B, Boss C, Barrett AJ. Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies. Blood. 2008 Jan 1;111(1):236-42. doi: 10.1182/blood-2007-08-108241. Epub 2007 Sep 17.

  PMID: 17875804 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

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

Study Officials

• Gregory J Kato, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: December 24, 2005
• First Posted: December 26, 2005
• Study Start: December 22, 2005
• Primary Completion: October 26, 2007
• Study Completion: October 26, 2007
• Last Updated: July 2, 2017

Record last verified: 2012-02-09

Locations

US (1)