Wilm's Tumor 1 (WT1) Peptide Vaccine for High Risk Hematologic Malignancy

NCT00433745 | Completed Phase 2 Results DMC

• 2 other identifiers: 07009107-H-0091
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine the safety and effectiveness of an experimental vaccine in controlling the abnormal growth of cells in patients with myelodysplastic syndrome (MDS, also known as myelodysplasia), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML). It will test whether the vaccine can increase the number of immune cells responding to the cancer and thereby slow progression of the illness, improve blood counts, reduce the need for transfusions of blood and platelets, or even achieve a disease remission. The vaccine contains part of a protein that is produced in large amounts by cells of patients with these cancers and an added substance called Montanide that helps the immune system respond to the vaccine. Sargramostim, another substances that boosts the immune response, is also given. Patients 18 to 85 years of age with MDS, AML, ALL or CML may be eligible for this study. Candidates are screened with a medical history, physical examination, blood tests, chest x-ray and bone marrow biopsy. Women of childbearing age also have a pregnancy test. Participants undergo the following:

• Chemotherapy entering the study.
• Leukapheresis to collect large amounts of white blood cells for infusion before vaccine administration.
• Participants may need placement of a central line (plastic tube, or catheter) in the upper part of the chest to be used for giving chemotherapy, blood or platelet transfusions, antibiotics and white blood cells, and for collecting blood samples.
• Weekly vaccine injections for nine weeks, given in the upper arm, upper leg or abdomen.
• Sargramostim injections following each vaccination.
• Standard of care treatment for MDS, AML, ALL or CML, which may include blood or platelet transfusions, growth factors, and drugs to control underlying disease and potential side effects of the vaccine.
• Weekly safety monitoring, including vital signs check, brief health assessment, blood tests and observation after the vaccination, on the day of each vaccination.
• Follow-up evaluations with blood tests and chest x-ray 3 weeks after the last vaccine dose and with blood tests and bone marrow biopsy 7 weeks after the last vaccine dose.

Conditions

Myelodysplastic Syndrome; Acute Myeloid Leukemia (AML); Chronic Myeloid Leukemia (CML)

Keywords

Myelodysplastic Syndrome (MDS); Acute Myelogenous Leukemia (AML); Chronic Myelogenous Leukemia (CML); Acute Lymphoblastic Leukemia (ALL); Wilm's Tumor-1 Peptide; Leukemia; Myelodysplastic Syndrome; MDS; Acute Myelogenous Leukemia; AML; Chronic Myelogenous Leukemia; CML; Acute Lymphoblastic Leukemia; ALL

Outcome Measures

Primary Outcomes (1)

• Cellular Immune Response

  Minimum criterion for a cellular immune response was defined as the emergence of detectable T cell frequency against Willm's tumor 1 (WT1) when the pre-study analysis found no response, or a twofold increase in T cell frequency at any post vaccination time point

  7 weeks after last dose of vaccine

Secondary Outcomes (1)

• Disease Response

  7 weeks after last dose of vaccine

Study Arms (1)

WT1 Peptide Vaccine

EXPERIMENTAL

WT1 vaccination (9 doses of WT-1:126-134 peptide (in Montanide adjuvant) administered concomitantly with GM-CSF (Sargramostim)

Drug: WT1 Peptide Vaccine

Interventions

WT1 Peptide Vaccine DRUG

WT1 vaccination (9 doses of WT-1:126-134 peptide (in Montanide adjuvant) administered concomitantly with GM-CSF (Sargramostim)

Also known as: Wilm's tumor 1 vaccine

WT1 Peptide Vaccine

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
• refractory anemia with excess of blasts (MDS-RAEB).
• refractory anemia with excess of blasts in transformation (MDS-RAEBt).
• secondary acute myelogenous leukemia (AML).
• relapsed or refractory acute or chronic myelogenous leukemias (AML).
• relapsed or refractory chronic myelogenous leukemias (CML) with accelerated phase or blast crisis
• relapsed or refractory acute lymphoblastic leukemia (high risk ALL).
• acute lymphoblastic leukemia (ALL) in complete remission.
• chronic myelomonocytic leukemia (CMML).
• Unsuitable for stem cell transplantation (age over sixty or unavailability of a fully-matched donor).
• made an informed decision not to undergo the transplant procedure.
• relapsed AML, CML, MDS or ALL post stem cell transplantation (SCT).
• HLA-A0201 positive.
• Ages 18 - 85 years.
• Off all lympho-ablative chemotherapeutic agents.

You may not qualify if:

• HIV positive (HIV-infected patients are immune-compromised and it is unlikely that these patients will be capable of mounting an immune response to the vaccine).
• Treatment with systemic corticosteroids within 7 days prior to study entry.
• Low bone marrow reserves (less than 20 percent cellularity).
• Serum creatinine greater than 2.5mg/dl or serum bilirubin greater than 4mg/dl (patients receiving fludarabine).
• Co-morbidity of such severity that it would preclude the patient's ability to tolerate protocol therapy.
• Predicted survival less than 3 months.
• Previous allergic reaction to Montanide Adjuvant.
• Pregnant or breast feeding (Pregnant and breast-feeding women are excluded from study because the effects of vaccination are not known and may pose a risk to the developing fetus. All female patients will have a urine pregnancy test, and only those that test negative will be allowed on study).
• Enrolled in another vaccine clinical trial during the study period.
• Inability to comprehend the investigational nature of the study and provide informed consent.
• Pregnant or lactating.
• Unfit to receive filgrastim (G-CSF) and undergo apheresis (abnormal blood counts, history of stroke, uncontrolled hypertension).
• HIV positive.
• Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the bone marrow transplant (BMT) treatment unlikely and making informed consent impossible.

Sponsors & Collaborators

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

Study Sites (1)

National Cancer Institute (NCI), 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• 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 BACKGROUND

• Rezvani K, Yong AS, Mielke S, Savani BN, Jafarpour B, Eniafe R, Le RQ, Musse L, Boss C, Childs R, John Barrett A. Lymphodepletion is permissive to the development of spontaneous T-cell responses to the self-antigen PR1 early after allogeneic stem cell transplantation and in patients with acute myeloid leukemia undergoing WT1 peptide vaccination following chemotherapy. Cancer Immunol Immunother. 2012 Jul;61(7):1125-36. doi: 10.1007/s00262-011-1187-z. Epub 2011 Dec 24.

  PMID: 22198310 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Although there was one partial response at 7 weeks, this patient went on to relapse as well. Consequently, all 4 patients had rapid relapses despite vaccination. Accrual was stopped at 4.

Results Point of Contact

• Title: Minoo Battiwalla, MD
• Organization: Hematology Branch, NHLBI

battiwam@nhlbi.nih.gov

301 827 0939

Study Officials

• John Barrett, MD

  National Institutes of Health- NHLBI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 9, 2007
• First Posted: February 12, 2007
• Study Start: February 1, 2007
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: July 8, 2014
• Results First Posted: July 8, 2014

Record last verified: 2014-06

Locations

US (1)