LeukemiaPhase 1CLIPANCT00078520
Treatment of B-CLL With Human IL-2 and CD40 Ligand and Plasmid Gene Modified Autologous Tumor Cells
A Phase 1 study testing Dose Level 1, Dose Level 2 and Dose Level 2- Fixed Dose in people with Leukemia and Leukemia, B-Cell, Chronic, run by Baylor College of Medicine at 1 site in United States.
Trial summary
This study is for patients that have chronic lymphocytic leukemia (CLL). This research study aims 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 patients body. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Leukemia, B-Cell, Chronic
- What is being tested?
- Dose Level 1, Dose Level 2 and Dose Level 2- Fixed Dose
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2003to 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 Richters transformation) with (group A) or without (group B) (Inclusion of B-CLL) 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 as below: 0 = up and about, no restriction, 1 = Ambulatory, no strenuous activity, 2 = Ambulatory, capable of self-care appropriate for age. Up and about > 50% of time, but unable to carry out any physical activities or attend school, 3 = Limited self-care only. Up and about < 50% of time, 4 = Disabled, no self care. Bedridden or confined to chair.
- Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study, and must have an absolute neutrophil count (ANC) of > / = 500/mL, absolute lymphocyte count (ALC) > / = 200/mL, hemoglobin > / = 8g/dL, and platelet count > / = 50,000/mL
- 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. This includes total abstinence, oral contraceptives, an intrauterine device, contraceptive implants under the skin, contraceptive injections (Depo-Provera). Contraceptive foam with a condom is allowed. The male partner should use a condom.
- 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 less than 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
- Richters transformation (aggressive non-Hodgkins 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 and CD40 Ligand and Plasmid Gene Modified Autologous Tumor Cells (CLIPA)
This study is for patients that have chronic lymphocytic leukemia (CLL). This research study aims 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 patients body. 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 experiments in animal and human cells in vitro demonstrated can help IL-2 perform better.
Some of these cells will then be put back into the patient's body. 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. An experimental treatment similar to this has already been used in children and similar experimental treatments are being used in adults with other cancers.
Read the detailed description
This is a phase I trial to assess the safety of a dose escalation of hCD40L-expressing autologous tumor cells with a fixed dose of recombinant hIL-2 gene transduced autologous leukemic blasts. All eligible patients will be treated with a minimum of three and up to six injections. There will be no use of placebo or control subjects.
- Conditions
- Leukemia, Leukemia, B-Cell, Chronic
- Being tested
- Dose Level 1, Dose Level 2, Dose Level 2- Fixed Dose
- Keywords
- Leukemia
- Medical subject headings
- Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dose Level 1Biological
IL-2-B-CLL 2 x 10^7; CD40L-B-CLL 0
Dose Level 2Biological
IL-2-B-CLL 2 x 10^7; CD40L-B-CLL 2 x 10^6
Dose Level 2- Fixed DoseBiological
IL-2-B-CLL 2 x 10^7; CD40L-B-CLL 2 x 10^7
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1 | Experimental | Patients may be treated with a minimum of 3-6 injections of their IL-2-secreting and CD40L-expressing autologous B-CLL cells, separated by one to two weeks in an immunological treatment window. 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 while an escalating number of CD40L-expressing B-CLL cells will be given at each dose-level. Receives: Biological: Dose Level 1 |
| Dose Level 2 | Experimental | Patients may be treated with a minimum of 3-6 injections of their IL-2-secreting and CD40L-expressing autologous B-CLL cells, separated by one to two weeks in an immunological treatment window. 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 while an escalating number of CD40L-expressing B-CLL cells will be given at each dose-level. Receives: Biological: Dose Level 2 |
| Dose Level- Fixed Dose | Experimental | Patients may be treated with a minimum of 3-6 injections of their IL-2-secreting and CD40L-expressing autologous B-CLL cells, separated by one to two weeks in an immunological treatment window. 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 while an escalating number of CD40L-expressing B-CLL cells will be given at each dose-level. Receives: Biological: Dose Level 2- Fixed Dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety of injections of autologous malignant B cells from B-CLL patients, which have been modified to secrete hIL-2 and hCD40L.
Measured: 12 weeks
Secondary outcomes (2)
anti-tumor immune responses
Measured: 15 years
obtain preliminary data on the anti-tumor effects of this treatment regimen.
Measured: 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2004 (estimated)
- Study startJan 2003
- 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 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
- Non-randomised
- 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, Study chair, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00078520
- Sponsor's protocol ID
- H11967
- Other IDs
- CLIPA
- Acronym
- CLIPA
- Status last verified
- Jan 2020
- First submitted
- 1 Mar 2004
- Last updated
- 21 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2020. 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 and CD40 Ligand and Plasmid Gene Modified Autologous Tumor Cells (CLIPA)
- ClinicalTrials.gov ID
- NCT00078520
- Acronym / sponsor ID
- CLIPA / H11967
- Conditions
- Leukemia, Leukemia, B-Cell, Chronic
- Keywords
- 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
- Jan 2003
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 2 Mar 2004 (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 study is for patients that have chronic lymphocytic leukemia (CLL). This research study aims 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 patients body. 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 experiments in animal and human cells in vitro demonstrated can help IL-2 perform better.
Some of these cells will then be put back into the patient's body. 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. An experimental treatment similar to this has already been used in children and similar experimental treatments are being used in adults with other cancers.
Detailed description
This is a phase I trial to assess the safety of a dose escalation of hCD40L-expressing autologous tumor cells with a fixed dose of recombinant hIL-2 gene transduced autologous leukemic blasts. All eligible patients will be treated with a minimum of three and up to six injections. There will be no use of placebo or control subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 | Experimental | Biological: Dose Level 1Patients may be treated with a minimum of 3-6 injections of their IL-2-secreting and CD40L-expressing autologous B-CLL cells, separated by one to two weeks in an immunological treatment window. 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 while an escalating number of CD40L-expressing B-CLL cells will be given at each dose-level. |
| Dose Level 2 | Experimental | Biological: Dose Level 2Patients may be treated with a minimum of 3-6 injections of their IL-2-secreting and CD40L-expressing autologous B-CLL cells, separated by one to two weeks in an immunological treatment window. 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 while an escalating number of CD40L-expressing B-CLL cells will be given at each dose-level. |
| Dose Level- Fixed Dose | Experimental | Biological: Dose Level 2- Fixed DosePatients may be treated with a minimum of 3-6 injections of their IL-2-secreting and CD40L-expressing autologous B-CLL cells, separated by one to two weeks in an immunological treatment window. 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 while an escalating number of CD40L-expressing B-CLL cells will be given at each dose-level. |
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 Richters transformation) with (group A) or without (group B) (Inclusion of B-CLL) 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 as below: 0 = up and about, no restriction, 1 = Ambulatory, no strenuous activity, 2 = Ambulatory, capable of self-care appropriate for age. Up and about > 50% of time, but unable to carry out any physical activities or attend school, 3 = Limited self-care only. Up and about < 50% of time, 4 = Disabled, no self care. Bedridden or confined to chair.
- Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study, and must have an absolute neutrophil count (ANC) of > / = 500/mL, absolute lymphocyte count (ALC) > / = 200/mL, hemoglobin > / = 8g/dL, and platelet count > / = 50,000/mL
- 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)
- Richters transformation (aggressive non-Hodgkins 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 |
|---|---|---|
| Dose Level 1IL-2-B-CLL 2 x 10^7; CD40L-B-CLL 0 | Biological | Dose Level 1 |
| Dose Level 2IL-2-B-CLL 2 x 10^7; CD40L-B-CLL 2 x 10^6 | Biological | Dose Level 2 |
| Dose Level 2- Fixed DoseIL-2-B-CLL 2 x 10^7; CD40L-B-CLL 2 x 10^7 | Biological | Dose Level- Fixed Dose |
Primary outcome
safety of injections of autologous malignant B cells from B-CLL patients, which have been modified to secrete hIL-2 and hCD40L.
Time frame: 12 weeks
2 secondary outcomes
anti-tumor immune responses
Time frame: 15 years
obtain preliminary data on the anti-tumor effects of this treatment regimen.
Time frame: 15 years
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 21 Jan 2020.
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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 study chair
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 Dose Level 1, Dose Level 2 and Dose Level 2- Fixed Dose in people with Leukemia and Leukemia, B-Cell, Chronic, 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 21 Jan 2020. 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 injections of autologous malignant B cells from B-CLL patients, which have been modified to secrete hIL-2 and hCD40L. (time frame: 12 weeks). 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 21 Jan 2020.