Leukemia,Myeloid, ChronicPhase 1NCT00027144
Study Using Vaccination With Heat Shock Protein 70 (HSP70) for the Treatment of CML in Chronic Phase
A Phase 1 study testing Heat Shock Protein 70 HSP70 in people with Leukemia,Myeloid, Chronic and Leukemia,Myeloid,Philadelphia-Positive, run by University of Connecticut at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia,Myeloid, Chronic, Leukemia,Myeloid,Philadelphia-Positive
- What is being tested?
- Heat Shock Protein 70 HSP70
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2000to Oct 2002
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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.
Who cannot join
- 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).
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Connecticut Health Center
Farmington, Connecticut, 06030
About this study
Official title: A Feasibility and Toxicity Study of Vaccination With HSP70 for the Treatment of Chronic Myelogenous Leukemia in the Chronic Phase
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.
Read the 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
- Being tested
- Heat Shock Protein 70 HSP70
- Keywords
- Leukemia, Vaccine
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Heat Shock Protein 70 HSP70Biological
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2001 (estimated)
- Study startDec 2000
- Study completionOct 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia,Myeloid, ChronicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants
Sponsor and investigators
- Lead sponsor
- University of Connecticut
- Sponsor type
- University, hospital or other
- Investigators
- Zihai Li, MD,Ph.D., Principal investigator, Assistant Professor Medicine and Tumor Immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00027144
- Sponsor's protocol ID
- 01-117
- Status last verified
- Nov 2001
- First submitted
- 27 Nov 2001
- Last updated
- 24 Jun 2005
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2005. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Feasibility and Toxicity Study of Vaccination With HSP70 for the Treatment of Chronic Myelogenous Leukemia in the Chronic Phase
- ClinicalTrials.gov ID
- NCT00027144
- Acronym / sponsor ID
- 01-117
- Keywords
- Leukemia, Vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants
- Lead sponsor
- University of ConnecticutUniversity, hospital or other
- Study start
- Dec 2000
- Study completion
- Oct 2002
- First posted
- 28 Nov 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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;
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Heat Shock Protein 70 HSP70 | Biological | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2005.
- UConn Web PageLink provided by the sponsor.
Related trials for Leukemia,Myeloid, Chronic
Not yet recruitingPhase 2
Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
Atypical Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia
Enrolling by invitationPhase 1
A Rollover Study for Continued Study Treatment and Ongoing Safety Monitoring
Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Chronic, B-Cell
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
RecruitingPhase 1
Phase 1 Study of 6MW5311 in Adults With Relapsed or Refractory Blood Cancers
AML, Multiple Myeloma
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zihai Li, MD,Ph.D. principal investigator
Assistant Professor Medicine and Tumor Immunology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Heat Shock Protein 70 HSP70 in people with Leukemia,Myeloid, Chronic and Leukemia,Myeloid,Philadelphia-Positive, run by University of Connecticut at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jun 2005. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2005.