Home
Search
Study Topics
Glossary
|
|
|
|
|
Sponsored by: |
National Heart, Lung, and Blood Institute (NHLBI) |
---|---|
Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00433745 |
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:
Condition | Intervention | Phase |
---|---|---|
Myelodysplastic Syndrome Acute Myeloid Leukemia (AML) Chronic Myeloid Leukemia (CML) |
Drug: WR 1 and PR 1 Peptide Vaccine |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study |
Official Title: | WTI Peptide Vaccination for Patients With High Risk Hematological Malignancies |
Estimated Enrollment: | 24 |
Study Start Date: | February 2007 |
Estimated Study Completion Date: | April 2013 |
Estimated Primary Completion Date: | April 2013 (Final data collection date for primary outcome measure) |
Leukemias and the related disorders myelodysplastic syndrome and myeloproliferative diseases represent a wide group of bone marrow stem cell malignancies. Some patients can be cured with chemotherapy or by allogeneic stem cell transplantation. However, standard treatment approaches are not effective for patients who become refractory to chemotherapy, those who relapse after transplantation and those with progressive disease. The management of such patients remains unsatisfactory and requires new treatment approaches other than chemotherapy.
The immunological graft-versus-leukemia (GVL) effect seen after allogeneic stem cell transplantation suggests that stimulating the patient's own T cell responses to hematological malignancies might also retard disease progression and even achieve disease remissions. WT1 was identified as a target vaccine antigen because this antigen is over-expressed by CD34 plus stem cells of most patients with myeloid and lymphoid malignancies but not by normal marrow cells. An HLA-A0201 restricted peptide derived from the WT protein is anticipated to induce T cell response against MDS and leukemic cells while sparing normal cells. Of note, about 40% of the population is HLA-A0201 positive.
Therefore we propose this Phase II trial, the second in a series of planned peptide vaccine research, which will evaluate the safety associated with an immunotherapy approach of lymphodepletion, lymphocyte infusion, and WT1 vaccination in select patients diagnosed with MDS, AML, ALL and CML. The WT1 vaccination will comprise of 9 doses of WT-1 peptide vaccines (in Montanide adjuvant) administered concomitantly with GM-CSF (Sargramostim).
The primary objectives will be to evaluate the efficacy and toxicity associated with the immunotherapy approach of lymphodepletion, lymphocyte infusion, and WT1 vaccination in selected patients with hematological malignancies.
Secondary objectives will include evaluation of disease response by following the numbers of WT1 expressing cells in blood, hematological measurements (reduction in marrow blast cells, changes in blood counts), transfusion dependence, and time to disease progression and survival.
The primary endpoint will be the side effects of treatment (toxicity and number of circulating WT1 specific T cells (efficacy ) measured through week 16 of the study (7 weeks after the last dose of vaccine).
Ages Eligible for Study: | 18 Years to 85 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
INCLUSION CRITERIA:
Diagnosed with
refractory anemia with excess of blasts (MDS-RAEB).
or
refractory anemia with excess of blasts in transformation (MDS-RAEBt).
or
secondary acute myelogenous leukemia (AML).
or
relapsed or refractory acute or chronic myelogenous leukemias (AML or CML).
or
relapsed or refractory acute lymphoblastic leukemia (high risk ALL).
or
acute lymphoblastic leukemia (ALL) in complete remission.
or
chronic myelomonocytic leukemia (CMML).
Unsuitable for stem cell transplantation (age over sixty or unavailability of a fully-matched donor).
or
made an informed decision not to undergo the transplant procedure.
or
relapsed AML, CML, MDS or ALL post stem cell transplantation (SCT).
Inclusion Criteria Donor (for post transplant subjects without available DLI cells):
EXCLUSION CRITERIA:
Exclusion Criteria-Donor (any of the following):
Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
Contact: TTY | 1-866-411-1010 |
United States, Maryland | |
National Cancer Institute (NCI), 9000 Rockville Pike | Recruiting |
Bethesda, Maryland, United States, 20892 |
Responsible Party: | National Institutes of Health ( A. John Barrett, M.D./National Heart, Lung, and Blood Institute ) |
Study ID Numbers: | 070091, 07-H-0091 |
Study First Received: | February 9, 2007 |
Last Updated: | August 24, 2009 |
ClinicalTrials.gov Identifier: | NCT00433745 History of Changes |
Health Authority: | United States: Federal Government |
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 |
Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Precancerous Conditions Hematologic Diseases Myelodysplastic Syndromes Myeloproliferative Disorders Leukemia, Myeloid Leukemia, Myeloid, Acute Leukemia |
Acute Myelocytic Leukemia Preleukemia Acute Myeloid Leukemia, Adult Wilms' Tumor Leukemia, Myelogenous, Chronic, BCR-ABL Positive Wilms Tumor Chronic Myelogenous Leukemia Bone Marrow Diseases Acute Lymphoblastic Leukemia |
Disease Neoplasms by Histologic Type Precancerous Conditions Hematologic Diseases Myelodysplastic Syndromes Myeloproliferative Disorders Leukemia, Myeloid Leukemia, Myeloid, Acute |
Leukemia Preleukemia Neoplasms Pathologic Processes Syndrome Leukemia, Myelogenous, Chronic, BCR-ABL Positive Bone Marrow Diseases |