Chronic Lymphocytic B-LeukemiaPhase 1CLIMATNCT00058786
Treatment of Chronic Lymphocytic B-Leukemia With IL-2 and CD-40 Autologous Tumor Cells
A Phase 1 study testing Injection of IL-2-secreting CD40L-expressing autologous B-CLL cells in people with Chronic Lymphocytic B-Leukemia, run by Baylor College of Medicine at 1 site in United States.
Trial summary
This is a research study to determine the safety and dosage of special cells that may make the patients own immune system fight the cancer. To do this, we will put a special gene into cancer cells that have been taken from the patient. This will be done in the laboratory. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic B-Leukemia
- What is being tested?
- Injection of IL-2-secreting CD40L-expressing autologous B-CLL cells
- Type of treatment
- Vaccines, Injection or infusion
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2002to Mar 2010
- 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
- Patients are eligible for administration of their vaccine if they present with B-CLL (not in Richter's transformation) with (group A) or without (group B) measurable disease. Untreated or complete remission patients will be enrolled for vaccine administration in a therapeutic (i.e. no chemotherapy) window of three months. If during these three months (necessary to complete the vaccine study) the patient presents with rapid clinical progression, he or she will be excluded from our current study and will receive treatment according to the standard institutional guidelines. IMPORTANT NOTE: Vaccine production for complete remission patients can only be achieved if tumor cells have been collected BEFORE entering complete remission.
- Patients must have a life expectancy of at least 10 weeks.
- Patients must have ECOG performance status of 0-2.
- Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study, and must have an absolute neutrophil count of >/= 500/uL, absolute lymphocyte count >/= 200/uL, hemoglobin >/= 8g/dL and platelet count >/= 50,000/uL.
- Patients must not be infected at time of protocol entry, and should not be receiving antibiotics (other than prophylactic trimethoprim sulfamethoxazole).
- Patients must be HIV-negative.
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- Patients must be willing to practice appropriate birth control methods during the study and for 3 months after the study is concluded.
- Patients must not be suffering from an autoimmune disease (including active graft-versus-host disease-GvHD, refractory immune thrombocytopenia-ITP or refractory autoimmune hemolytic anemia-AIHA) and should not be receiving immunosuppressive drugs.
- Patients must have adequate liver function (total bilirubin </= 1.5mg/dl, SGOT </= 2 times normal, normal prothrombin time).
- Patients must have adequate renal function (creatinine < 3 times normal for age or creatinine clearance > 80mg/min/1.73m2).
- Patients must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side-effects. Patients will be given a copy of the consent form.
- Patient must not have received treatment with other investigational agents within the last 4 weeks.
Who cannot join
- Richter's transformation (aggressive non-Hodgkin's lymphoma)
- active infection
- significant autoimmune disease (including active GvHD, ITP and AIHA)
- requirement for immunosuppressive drugs
- inadequate liver and/or renal function
- pregnancy or lactation
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- refusal to practice birth control methods
- seropositive for HIV
- life expectancy less than 10 weeks
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment of Chronic Lymphocytic B-Leukemia (B-CLL) With Human IL-2 Gene Modified and Human CD40 Ligand-Expressing Autologous Tumor Cells
This is a research study to determine the safety and dosage of special cells that may make the patients own immune system fight the cancer. To do this, we will put a special gene into cancer cells that have been taken from the patient. This will be done in the laboratory. This gene will make the cells produce interleukin 2 (IL-2), which is a natural substance that may help the immune system kill cancer cells. Additionally, we will stimulate the cancer cells with another natural protein called CD40 ligand (CD40L), which preclinical human and animal studies suggest will help IL-2 perform better. Some of these cells will then be put back into the body. The cells are grown with normal embryonic fibroblasts. Studies of cancers in animals and in cancer cells that are grown in laboratories suggest that combining substances like IL-2 and CD40L helps the body kill cancer cells.
The purpose of this study is to learn the side effects and the safest effective dose of these special cells on the disease
Read the detailed description
Before starting treatment some of the cancer cells will be taken from the patient and separated in the laboratory. A specially produced human virus (adenovirus) that carries the IL-2 gene will be put into the cells. The rest of the cancer cells will be stimulated to express on their surface a substance called the human CD40 ligand. These substances (IL-2 and CD40L), already naturally present in the body, are meant to help the immune system fight the cancer.
In this study, the modified cancer cells will be injected under the skin. There will be up to six shots. We do not know the best amount of special cells to use, so different patients will get different numbers of cells.
After the first three shots (if more modified cancer cells are available), patients may be able to have three additional shots. After they have received six shots, they may be able to have additional shots if the cancer has gotten smaller and more of the cells are available.
A complete history and physical examination is necessary before a patient can be enrolled in the study. A physical examination will also be performed weekly for ten weeks after the injection, then on week twelve, then monthly for one year. Patients will then have yearly checkups for the next fifteen years. After the first and second shots, we will remove some of the modified cells that have been injected under the skin, to study them. We will do this by removing a section of skin (referred to as a skin biopsy) at the place where the cells were injected. These tests will help us to see whether or not the modified cells are killing cancer cells and whether or not the cancer cells are growing. If we suspect the cancer cells are growing, we may repeat this procedure after the third and fourth shots.
To study how the immunity is working in the patients system, we will take blood samples before the first injection, then weekly for 10 weeks, on week 12, once a month for a year, and then eventually once a year for fifteen years. These blood samples must be taken at The Methodist Hospital. The total amount of blood that will be obtained is approximately two to three tablespoonfuls, which is considered a safe amount. If the patient has additional injections, blood will be drawn prior to each injection. Additional office visits may be necessary.
If the patient decides to withdraw at any time during the study both samples and data collected during the study will be maintained with identifiers for safety reasons.
- Conditions
- Chronic Lymphocytic B-Leukemia
- Being tested
- Injection of IL-2-secreting CD40L-expressing autologous B-CLL cells
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Injection of IL-2-secreting CD40L-expressing autologous B-CLL cellsBiological
Patients may be treated with a minimum of three up to six injections of their IL-2-secreting and CD40L-expressing autologous B-CLL cells, separated by one to two weeks in an immunological treatment window, i.e. in the absence of concurrent cytotoxic therapy. Any patient whose disease regresses after the administration of 6 injections may be offered further injections (i.e. more than 6 injections) of tumor vaccine at the dose level previously administered, if enough vaccines are available. Patients will receive a fixed dose of IL-2 secreting B-CLL cells throughout the entire treatment protocol (see Section 5.8), determined by previous studies in acute leukemia and in neuroblastoma, in which this level of IL-2 production has been safe. The dose escalation of CD40L-expressing cells is designed to reach the IL2/CD40L ratio shown to be effective in our preclinical models of neuroblastoma and lymphoma.
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of 3-6 SQ injections of autologous malignant B cells from chronic B-CLL pts, which have been modified ex vivo to secrete human interleukin-2 (hIL-2) and to express human CD40 ligand (hCD40L).
Measured: 3 mths
Secondary outcomes (2)
To determine whether MHC- restricted or unrestricted anti-tumor immune responses are induced by SC injections of B-CLL cells which have been modified ex vivo to secrete hIL-2 and to express hCD40L
Measured: 15 yrs
To obtain preliminary data on the anti-tumor effects of this treatment regimen
Measured: 15 yrs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2003 (estimated)
- Study startDec 2002
- Primary completionMar 2010
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic B-LeukemiaStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Responsible party
- Principal investigator, Malcolm Brenner, Baylor College of Medicine
- Investigators
- Malcolm K Brenner, MD, Principal investigator, Center for Cell and Gene Therapy, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00058786
- Sponsor's protocol ID
- H11541
- Other IDs
- Climat
- Acronym
- CLIMAT
- Status last verified
- May 2012
- First submitted
- 11 Apr 2003
- Last updated
- 23 May 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Chronic Lymphocytic B-Leukemia (B-CLL) With Human IL-2 Gene Modified and Human CD40 Ligand-Expressing Autologous Tumor Cells
- ClinicalTrials.gov ID
- NCT00058786
- Acronym / sponsor ID
- CLIMAT / H11541
- Conditions
- Chronic Lymphocytic B-Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Study start
- Dec 2002
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 15 Apr 2003 (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.
This is a research study to determine the safety and dosage of special cells that may make the patients own immune system fight the cancer. To do this, we will put a special gene into cancer cells that have been taken from the patient. This will be done in the laboratory. This gene will make the cells produce interleukin 2 (IL-2), which is a natural substance that may help the immune system kill cancer cells. Additionally, we will stimulate the cancer cells with another natural protein called CD40 ligand (CD40L), which preclinical human and animal studies suggest will help IL-2 perform better. Some of these cells will then be put back into the body. The cells are grown with normal embryonic fibroblasts. Studies of cancers in animals and in cancer cells that are grown in laboratories suggest that combining substances like IL-2 and CD40L helps the body kill cancer cells.
The purpose of this study is to learn the side effects and the safest effective dose of these special cells on the disease
Detailed description
Before starting treatment some of the cancer cells will be taken from the patient and separated in the laboratory. A specially produced human virus (adenovirus) that carries the IL-2 gene will be put into the cells. The rest of the cancer cells will be stimulated to express on their surface a substance called the human CD40 ligand. These substances (IL-2 and CD40L), already naturally present in the body, are meant to help the immune system fight the cancer.
In this study, the modified cancer cells will be injected under the skin. There will be up to six shots. We do not know the best amount of special cells to use, so different patients will get different numbers of cells.
After the first three shots (if more modified cancer cells are available), patients may be able to have three additional shots. After they have received six shots, they may be able to have additional shots if the cancer has gotten smaller and more of the cells are available.
A complete history and physical examination is necessary before a patient can be enrolled in the study. A physical examination will also be performed weekly for ten weeks after the injection, then on week twelve, then monthly for one year. Patients will then have yearly checkups for the next fifteen years. After the first and second shots, we will remove some of the modified cells that have been injected under the skin, to study them. We will do this by removing a section of skin (referred to as a skin biopsy) at the place where the cells were injected. These tests will help us to see whether or not the modified cells are killing cancer cells and whether or not the cancer cells are growing. If we suspect the cancer cells are growing, we may repeat this procedure after the third and fourth shots.
To study how the immunity is working in the patients system, we will take blood samples before the first injection, then weekly for 10 weeks, on week 12, once a month for a year, and then eventually once a year for fifteen years. These blood samples must be taken at The Methodist Hospital. The total amount of blood that will be obtained is approximately two to three tablespoonfuls, which is considered a safe amount. If the patient has additional injections, blood will be drawn prior to each injection. Additional office visits may be necessary.
If the patient decides to withdraw at any time during the study both samples and data collected during the study will be maintained with identifiers for safety reasons.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- 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 (12 listed)
- Patients are eligible for administration of their vaccine if they present with B-CLL (not in Richter's transformation) with (group A) or without (group B) measurable disease. Untreated or complete remission patients will be enrolled for vaccine administration in a therapeutic (i.e. no chemotherapy) window of three months. If during these three months (necessary to complete the vaccine study) the patient presents with rapid clinical progression, he or she will be excluded from our current study and will receive treatment according to the standard institutional guidelines. IMPORTANT NOTE: Vaccine production for complete remission patients can only be achieved if tumor cells have been collected BEFORE entering complete remission.
- Patients must have a life expectancy of at least 10 weeks.
- Patients must have ECOG performance status of 0-2.
- Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study, and must have an absolute neutrophil count of >/= 500/uL, absolute lymphocyte count >/= 200/uL, hemoglobin >/= 8g/dL and platelet count >/= 50,000/uL.
- Patients must not be infected at time of protocol entry, and should not be receiving antibiotics (other than prophylactic trimethoprim sulfamethoxazole).
Key exclusion criteria (9 listed)
- Richter's transformation (aggressive non-Hodgkin's lymphoma)
- active infection
- significant autoimmune disease (including active GvHD, ITP and AIHA)
- requirement for immunosuppressive drugs
- inadequate liver and/or renal function
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 |
|---|---|---|
| Injection of IL-2-secreting CD40L-expressing autologous B-CLL cellsPatients may be treated with a minimum of three up to six injections of their IL-2-secreting and CD40L-expressing autologous B-CLL cells, separated by one to two weeks in an immunological treatment window, i.e. in the absence of concurrent cytotoxic therapy. Any patient whose disease regresses after the administration of 6 injections may be offered further injections (i.e. more than 6 injections) of tumor vaccine at the dose level previously administered, if enough vaccines are available. Patients will receive a fixed dose of IL-2 secreting B-CLL cells throughout the entire treatment protocol (see Section 5.8), determined by previous studies in acute leukemia and in neuroblastoma, in which this level of IL-2 production has been safe. The dose escalation of CD40L-expressing cells is designed to reach the IL2/CD40L ratio shown to be effective in our preclinical models of neuroblastoma and lymphoma. | Biological | – |
Primary outcome
Safety of 3-6 SQ injections of autologous malignant B cells from chronic B-CLL pts, which have been modified ex vivo to secrete human interleukin-2 (hIL-2) and to express human CD40 ligand (hCD40L).
Time frame: 3 mths
2 secondary outcomes
To determine whether MHC- restricted or unrestricted anti-tumor immune responses are induced by SC injections of B-CLL cells which have been modified ex vivo to secrete hIL-2 and to express hCD40L
Time frame: 15 yrs
To obtain preliminary data on the anti-tumor effects of this treatment regimen
Time frame: 15 yrs
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 23 May 2012.
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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.
Malcolm K Brenner, MD principal investigator
Center for Cell and Gene Therapy, Baylor College of Medicine
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 Injection of IL-2-secreting CD40L-expressing autologous B-CLL cells in people with Chronic Lymphocytic B-Leukemia, run by Baylor College of Medicine 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 12 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 23 May 2012. 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.
What does the primary outcome measure?
Safety of 3-6 SQ injections of autologous malignant B cells from chronic B-CLL pts, which have been modified ex vivo to secrete human interleukin-2 (hIL-2) and to express human CD40 ligand (hCD40L). (time frame: 3 mths). It is what the study was designed to measure, not a finding.
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 23 May 2012.