Study Using Vaccination With Heat Shock Protein 70 (HSP70) for the Treatment of CML in Chronic Phase - Full Text View

Sponsor:	University of Connecticut
Information provided by:	University of Connecticut Health Center
ClinicalTrials.gov Identifier:	NCT00027144

Purpose

Description: The trial is designed to determine the response of the immune system of patients with CML to a vaccine made from their own tumor. Researchers believe that this particular vaccine, which is made from purified heat shock proteins taken from each patient's tumor, alerts the body's immune system to recognize and attack invading cancer. To be considered potentially eligible for this study you must have CML in the chronic phase.

Length/Duration: Vaccinations will be administered weekly for eight weeks. One clinic follow up visit will be scheduled two weeks after the final vaccination.

Condition	Intervention	Phase
Leukemia,Myeloid, Chronic Leukemia,Myeloid,Philadelphia-Positive	Biological: Heat Shock Protein 70 HSP70	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Feasibility and Toxicity Study of Vaccination With HSP70 for the Treatment of Chronic Myelogenous Leukemia in the Chronic Phase

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

U.S. FDA Resources

Further study details as provided by University of Connecticut Health Center:

Estimated Enrollment:	10
Study Start Date:	December 2000
Estimated Study Completion Date:	October 2002

Detailed Description:

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,

an increase in peripheral blood of IFN-gamma producing CD8+ T-lymphocytes which are reactive to the autologous bcr/abl positive peripheral mononuclear cells
an increase of PR-1 specific CTLs by PR1-HLA-A2 tetramer techniques in patients who are HLA-A2 positive
the change of immunophenotype of peripheral lymphocytes
the cytogenetic remission of Philadelphia chromosome from the bone marrow

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00027144

Locations

United States, Connecticut
University of Connecticut Health Center
Farmington, Connecticut, United States, 06030

Sponsors and Collaborators

University of Connecticut

Investigators

Principal Investigator:

Zihai Li, MD,Ph.D.

Assistant Professor Medicine and Tumor Immunology

More Information

Additional Information:

UConn Web Page This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	01-117
Study First Received:	November 27, 2001
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00027144 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Connecticut Health Center:

Leukemia
Vaccine

Additional relevant MeSH terms:

Leukemia
Neoplasms
Neoplasms by Histologic Type
Hematologic Diseases

Myeloproliferative Disorders
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Bone Marrow Diseases

ClinicalTrials.gov processed this record on November 05, 2009