A Feasibility and Toxicity Study of Vaccination With HSP70 for the Treatment of Chronic Myelogenous Leukemia in the Chronic Phase
18 Years
N/A
Both
Leukemia,Myeloid, Chronic, Leukemia,Myeloid,Philadelphia-Positive
Trial Information
A Feasibility and Toxicity Study of Vaccination With HSP70 for the Treatment of Chronic Myelogenous Leukemia in the Chronic Phase
Rational for immunotherapy of CML
Conceptually,CML in chronic phase is the best model for immunological intervention. It is a
disease as a result of chromosomal translocation, which generates a true tumor-specific
antigen. Patients in chronic phase have relatively preserved immune function for a prolonged
period of time. Studies have indeed shown that peptides spanning the junctional region of
both the bcr/abl and abl/bcr fusion proteins can bind to major histocompatibility complex
(MHC) class I molecules (Berke et al. 2000). Vaccination of patients with bcr/abl breakpoint
fusion peptides generates specific immune responses (Pinilla-Ibarz et al. 2000). In
addition, for patients relapsed after bone marrow or stem cell transplant, donor lymphocyte
infusion is effective in inducing a majority of them into remission. The role of donor
lymphocyte infusion has proven the original concept of graft versus leukemia effect and the
effectiveness of immunotherapy, in practice, towards CML (Dazzi et al. 1999). More recently,
it was found that the presence of cytotoxic T lymphocytes (CTL) against HLA-A2-restricted
myeloid-specific antigen proteinase 3 correlates significantly with cytogenetic remission of
CML treated either with IFN or stem cell transplant (Molldrem et al. 2000), which provides
strong evidence for a role of T cell immunity in clearing malignant cells.
Current proposal and hypothesis:
Based on the established roles of HSPs in T cell immunity and a large body of preclinical
and clinical safety data, we propose to initiate a pilot study to test the feasibility of
immunization with autologous tumor-derived HSP70 in the treatment of CML in chronic phase.
This study will facilitate more clinical trials in the future, testing the ultimate
hypothesis that the combination of the cytostatic therapy such as IFN and STI571, with
specific immunomodulator such as HSP70 offers the best chance of eradication of CML. A total
of 10 eligible patients will be enrolled in the study. All eligible patients will undergo
aphaeresis to collect peripheral blood mononuclear cells. The autologous HSP70 is then
purified using the standard protocol. After passing the established sterility testing, the
patients are immunized intradermally with 50 micrograms HSP70 for a total of 8 injections in
2 months. They may receive their standard therapy during this time. In addition to
collecting the feasibility and toxicity data, the development of anti-tumor immunity will be
measured by,
1. an increase in peripheral blood of IFN-gamma producing CD8+ T-lymphocytes which are
reactive to the autologous bcr/abl positive peripheral mononuclear cells
2. an increase of PR-1 specific CTLs by PR1-HLA-A2 tetramer techniques in patients who are
HLA-A2 positive
3. the change of immunophenotype of peripheral lymphocytes
4. the cytogenetic remission of Philadelphia chromosome from the bone marrow
Inclusion Criteria
ELIGIBILITY
Inclusion:
- ECOG Performance Score(PS) less than 2.
- Must be at least 18 years of age and capable of giving informed consent.
- Must be less than three years from the original diagnosis of Philadelphia chromosome
positive CML in chronic phase.
- Patient is not in cytogenetic remission.
- No anticipation of bone marrow or stem cell transplant for six months unless these
therapies are deemed necessary by a treatment physician due to the evolution of the
disease;
- Concurrent treatment with hydroxyurea or Gleevec is allowed.PAST treatment with IFN
alpha, Ara-C or other cytoxic agents is allowed
- Must not have any serious illness such that their medical condition might be
compromised by participation in the study.
- Must have adequate renal function (serum creatinine < 2.0), hepatic function
(bilirubin and transaminase less than 2.0 x of the upper normal limit).
- Must not be on corticosteroid therapy, or other immunosuppressive medications.
Exclusion
- Patients with an ECOG Performance Score greater than or equal to 2.
- Patient is greater than or equal to 3 years out from the original diagnosis.
- Significant anemia (Hemoglobin < 10 g/dl) and thrombocytopenia (platelet < 20,000/ml)
requiring transfusion.
- Peripheral blast count is over 10%.
- Positive urine or blood pregnancy test.
- Impaired renal function (serum creatinine > 2.0), hepatic function (bilirubin and
transaminase more than 2.0 x of the upper normal limit).
- Patient with significant active infection requiring hospitalization at the time of
enrollment.
- Patient with significant behavioral or psychological problems that prevent adequate
follow-up.
- Concurrent treatment with IFN alpha Ara-C or other cytotoxic agents (Gleevec and
hydroxyurea are allowed.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Zihai Li, MD,Ph.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
Assistant Professor Medicine and Tumor Immunology
Authority:
United States: Food and Drug Administration
Study ID:
01-117
NCT ID:
NCT00027144
Start Date:
December 2000
Completion Date:
October 2002
Related Keywords:
- Leukemia,Myeloid, Chronic
- Leukemia,Myeloid,Philadelphia-Positive
- Leukemia
- Vaccine
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Name | Location |
|---|---|
| University of Connecticut Health Center | Farmington, Connecticut 06360-7106 |
