Clinical trial NCT00433745
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
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Start date: 2007-02-01; Completion date: 2009-11-01
Enrollment: 4 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Detailed description:
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. Wilm's Tumor 1 (WT1) was identified as a target vaccine antigen because this antigen is over-expressed by cluster of differentiation 34 (CD34) plus stem cells of most patients with myeloid and lymphoid malignancies but not by normal marrow cells. A human leukocyte antigen (HLA-A0201) restricted peptide derived from the Wilm's Tumor (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 granulocyte macrophage- colony stimulating factor (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).

Arms: arm 1: WT1 vaccination (9 doses of WT-1:126-134 peptide (in Montanide adjuvant) administered concomitantly with GM-CSF (Sargramostim)
Interventions: intervention 1: WT1 Peptide Vaccine
Intervention descriptions: intervention 1: WT1 vaccination (9 doses of WT-1:126-134 peptide (in Montanide adjuvant) administered concomitantly with GM-CSF (Sargramostim)

Protocol documents: