Vaccine Therapy and Imatinib Mesylate in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Vaccines made from gene-modified cancer cells may help the body build an effective immune response to kill cancer cells. Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving vaccine therapy together with imatinib mesylate may be an effective treatment for chronic myelogenous leukemia. PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy when given together with imatinib mesylate in treating patients with chronic phase chronic myelogenous leukemia.

Detailed Description
-----------------
OBJECTIVES: Primary Determine the maximum tolerated dose of GM-K562 cell vaccine when administered with imatinib mesylate in patients with persistent chronic phase chronic myelogenous leukemia in first hematologic response. Determine the safety and toxic effects of GM-K562 cell vaccination in these patients. Secondary Determine the disease response by serial BCR-ABL quantitative polymerase chain reaction measurements in patients treated with this regimen. Determine the development of tumor immunity in patients treated with this regimen. OUTLINE: This is a dose-escalation study of GM-K562. Patients continue to receive oral imatinib mesylate at the same stable dose as before study entry. Patients receive GM-K562 subcutaneously on days 1, 8, 15, 29, 43, 57, 85, 113, and 141 in the absence of disease progression or unacceptable toxicity. Cohorts of 10 patients receive escalating doses of GM-K562 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 10 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed periodically for 20 years. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Official Title
-----------------
Vaccination for CML Patients With Persistent Disease on Imatinib Mesylate

Conditions
-----------------
Leukemia

Intervention / Treatment
-----------------
* Biological: GM-K562 cell vaccine
* Drug: imatinib mesylate


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Diagnosis of chronic myelogenous leukemia Chronic phase disease Philadelphia chromosome positive disease Disease in first complete hematologic response, defined by all of the following: Complete normalization of peripheral blood counts with WBC < 10,000/mm^3 Platelet count < 450,000/mm^3 No immature cells (e.g., myelocytes, metamyelocytes, or blasts) in the peripheral blood Persistent molecular evidence of disease Detectable BCR-ABL transcript by quantitative polymerase chain reaction Less than 2 log reduction in peripheral blood or bone marrow BCR-ABL transcripts levels compared to a standardized baseline Must have received imatinib mesylate for > 1 year of which the last 3 months were at stable dose ≥ 300 mg/day PATIENT CHARACTERISTICS: Not pregnant or nursing Fertile patients must use effective contraception Negative pregnancy test No known HIV ALT or AST ≤ 3 times upper limit of normal Oxygen saturation ≥ 93% at room air No history of recent acute myocardial infarction No history of unstable angina No pulmonary decomposition requiring hospitalization within the past 3 months No concurrent and/or uncontrolled psychiatric or medical condition that would preclude study compliance PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior allogeneic stem cell transplantation At least 2 months since other prior experimental therapy At least 6 months since prior participation in another vaccine study No concurrent systemic immunosuppressive medication

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: GM-K562 cell vaccine|Once weekly for 3 vaccination, then every other week for 3 vaccinations, and then every month for 3 vaccinations until the participant has received a total of 9 vaccinations|
|Drug: imatinib mesylate|Participants will continue on current dose|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Toxicity | To assess the safety and toxicity of GM-K462 vaccination in CP CML patients who have acheived a complete hematologic response to imatinib. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Response | To assess disease response after GM-K562 vaccination by serial BCR-ABL Q-PCR measurements | 3 years | 
| Tumor immunity | To characterize the development of tumor immunity in response to vaccination with GM-K562 cells | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
chronic phase chronic myelogenous leukemia, Philadelphia chromosome positive chronic myelogenous leukemia