LeukemiaPhase 1NCT00058799
Treating High Risk Leukemia With CD40 Ligand & IL-2 Gene Modified Tumor Vaccine
A Phase 1 study testing Dose Level 1, Dose Level 2 and Dose Level 3 in people with Leukemia, run by Baylor College of Medicine at 3 sites in United States.
Trial summary
This research study is to determine the safety and dosage of special cells that may make the patients own immune system fight the leukemia. To do this we will put special genes into cells called fibroblasts that we have grown in the laboratory from a skin sample. Read more about this study
- Who is it for?
- Ages Up to 75 years
- Conditions the study is for
- Leukemia
- What is being tested?
- Dose Level 1, Dose Level 2 and Dose Level 3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 3 sitesUnited States
- Study dates
- Jun 1999to Jun 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 Up to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients less than or equal to 75 years old with lymphoid (pre-B, B, T, non B-, non T, or Burkitt if bone marrow blasts > 20%) or acute myeloid leukemia (M0 to M7) or myelodysplastic syndrome and with: Disease that has entered remission with chemotherapy and/or bone marrow transplantation, but is considered to be at high risk of relapse. or Primary, or relapsed treatment-refractory disease who, at the time of reinjection of the tumor vaccine, are at a state of complete or partial cytological remission disease (<20% blasts infiltrating the bone marrow) after a second/higher line of conventional and/or high dose chemotherapy.
- Patients must have a life expectancy of at least 10 weeks.
- Patients must have ECOG performance status of 0-2 as below:
- Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study, and have an absolute neutrophil count >500/mm3, absolute lymphocyte count >200/mm3, and platelet count >50,000/mm3.
- Patients must not have active GvHD at the time of protocol entry.
- Patient has not received high dose steroids within the last week or other immunosuppressive drugs within a week (or longer as indicated by the half life of the agent)
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- Patients must not be infected at time of protocol entry, and should not be receiving antibiotics (other than prophylactic Septra.)
- Patients must not be HIV-positive.
- Patients must have adequate liver function (bilirubin<1.5 mg% SGOT<2x normal, normal prothrombin time).
- Patients must have transduced cells available that are demonstrably >20% CD40L expressing fibroblasts and producing>150 pg IL-2/10 6 cell/24 hr.
- Patients or legal guardians 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 or their guardians will be given a copy of the consent form.
- Patient must not have received treatment with other investigational agents within the last 4 weeks.
- Patients must be willing to utilize one of the more effective birth control methods during the study and for 3 months after the study is concluded. The male partner should use a condom.
Who cannot join
- Rapidly progressive/refractory disease (>20% blasts infiltrating the bone marrow)
- Life expectancy < 10 weeks
- Active infection
- Need for concomitant drugs except analgesics
- Pregnancy or lactation
- Seropositive for HIV
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Texas Children's Hospital GCRC
Houston, Texas, 77030
Texas Children's Hospital
Houston, Texas, 77030
The Methodist Hospital
Houston, Texas, 77030
About this study
Official title: Treatment of High Risk Acute Leukemia With CD40 Ligand and IL-2 Gene Modified Autologous Skin Fibroblasts and Tumor Cells
This research study is to determine the safety and dosage of special cells that may make the patients own immune system fight the leukemia. To do this we will put special genes into cells called fibroblasts that we have grown in the laboratory from a skin sample. The genes we put in these fibroblasts make them produce substances called CD40 Ligand (CD40L) and interleukin-2 (IL-2). These are natural substances that may help the immune system kill leukemia cells. Some of these fibroblasts producing CD40L and IL-2 mixed with a small quantity of the leukemic cells will then be put back into the body.
Studies of cancers in animals and in cell lines suggest that substances like CD40L and IL-2 when mixed with cancer cells do help the body to recognize and kill these cancer cells. A treatment using IL-2 has been previously used in more than 40 children with neuroblastoma and similar treatments are being used in adults with other cancers. Some of the patients have shown significant tumor responses. However, we do not know if this treatment will work and we do not know the right amount of each of the special cells to use, so different patients will get different combination and numbers of cells.
The purpose of this study is to learn the side effects and safe dosage of these special cells.
Read the detailed description
Before starting in the treatment part of this study, leukemia cells and skin fibroblasts will be collected from the patient - called "procurement" - to allow us to make the vaccine. These leukemia cells are taken from either peripheral blood, leukopheresis product or bone marrow. The fibroblasts will be prepared in the laboratory with specially produced human viruses (adenoviruses) that carry the IL-2 or the CD40L gene. The viruses will "drop off" the genes inside the fibroblasts. The CD40L and IL-2 genes are meant to help stimulate the immune system to fight the leukemia. The modified fibroblasts will be injected with a number of leukemic cells under the skin. All the cells will be irradiated before injection to stop them growing. Patients will receive three shots. Depending on the response, patients may be able to have three additional shots.
In order to collect the skin fibroblasts at the very beginning of the study, and then during the study, we will perform small skin biopsies. In particular before the second shot, and then again about 1 week later, we will look for both the modified and leukemia cells that have been re-injected under the skin. We will do this by taking a skin biopsy from the place where the cells were injected. The area where the skin biopsy will be obtained will be sterilized and then numbed with a local acting agent. The skin will be removed with a "tissue punch" which will cut a circle of approximately 1/4th of an inch into the skin. The site where the skin was removed will be closed with suture, tape or stitches. The area will be covered with dry gauze and adhesive tape. These tests are to see whether the shots are killing leukemia cells and to make sure leukemia cells are not growing at the injection site.
To study how the immunity is working in the system, we will take blood samples before 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 samples will be approximately 1 tablespoons of blood, 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.
Also, patients will need to have a bone marrow test before enrolling on the study and at week 12. If the patient is not responding, they may have treatment with other chemotherapy or radiation. Patients will need to come to the clinic on the days of blood drawing and to be seen at Texas Children's Cancer Center/The Methodist Hospital at weekly intervals for 10 weeks, then every other week for 6 weeks, and then monthly for a year. Thereafter, patients will either be seen in the clinic or contacted by one of the research staff working on this study once a year for 15 years. Additional visits may be necessary.
- Conditions
- Leukemia
- Being tested
- Dose Level 1, Dose Level 2, Dose Level 3
- Medical subject headings
- Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dose Level 1Biological
Leukemic Blasts 2 x 10^7; IL-2 Fibroblasts 2 x 10^7; CD40L Fibroblasts 2 x 10^5
Dose Level 2Biological
Leukemic Blasts 2 x 10^7; IL-2 Fibroblasts 2 x 10^7; CD40L Fibroblasts 2 x 10^5
Dose Level 3Biological
Leukemic Blasts 2 x 10^7; IL-2 Fibroblasts 2 x 10^7; CD40L Fibroblasts 4.2 x 10^7
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1 | Experimental | Patients are treated with up to six injections of their gene-modified CD40L and IL-2 skin fibroblasts and leukemic blasts, separated by one-two weeks in an immunological treatment window. Receives: Biological: Dose Level 1 |
| Dose Level 2 | Experimental | Patients are treated with up to six injections of their gene-modified CD40L and IL-2 skin fibroblasts and leukemic blasts, separated by one-two weeks in an immunological treatment window. Receives: Biological: Dose Level 2 |
| Dose Level 3 | Experimental | Patients are treated with up to six injections of their gene-modified CD40L and IL-2 skin fibroblasts and leukemic blasts, separated by one-two weeks in an immunological treatment window. Receives: Biological: Dose Level 3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
• To determine the safety of up to six subcutaneous (SC) injections of autologous tumor cells admixed with autologous gene-modified skin fibroblasts. These fibroblasts are modified ex vivo to express the human CD40 Ligand (hCD40L) and interleukin-2 (hIL
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 posted15 Apr 2003 (estimated)
- Study startJun 1999
- Primary completionJun 2010
- Study completionJun 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
- 11 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, PhD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00058799
- Sponsor's protocol ID
- H6408-Leu Leu
- Status last verified
- Jan 2020
- First submitted
- 11 Apr 2003
- Last updated
- 21 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
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 High Risk Acute Leukemia With CD40 Ligand and IL-2 Gene Modified Autologous Skin Fibroblasts and Tumor Cells
- ClinicalTrials.gov ID
- NCT00058799
- Acronym / sponsor ID
- H6408-Leu Leu
- Conditions
- Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 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
- Jun 1999
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 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 research study is to determine the safety and dosage of special cells that may make the patients own immune system fight the leukemia. To do this we will put special genes into cells called fibroblasts that we have grown in the laboratory from a skin sample. The genes we put in these fibroblasts make them produce substances called CD40 Ligand (CD40L) and interleukin-2 (IL-2). These are natural substances that may help the immune system kill leukemia cells. Some of these fibroblasts producing CD40L and IL-2 mixed with a small quantity of the leukemic cells will then be put back into the body.
Studies of cancers in animals and in cell lines suggest that substances like CD40L and IL-2 when mixed with cancer cells do help the body to recognize and kill these cancer cells. A treatment using IL-2 has been previously used in more than 40 children with neuroblastoma and similar treatments are being used in adults with other cancers. Some of the patients have shown significant tumor responses. However, we do not know if this treatment will work and we do not know the right amount of each of the special cells to use, so different patients will get different combination and numbers of cells.
The purpose of this study is to learn the side effects and safe dosage of these special cells.
Detailed description
Before starting in the treatment part of this study, leukemia cells and skin fibroblasts will be collected from the patient - called "procurement" - to allow us to make the vaccine. These leukemia cells are taken from either peripheral blood, leukopheresis product or bone marrow. The fibroblasts will be prepared in the laboratory with specially produced human viruses (adenoviruses) that carry the IL-2 or the CD40L gene. The viruses will "drop off" the genes inside the fibroblasts. The CD40L and IL-2 genes are meant to help stimulate the immune system to fight the leukemia. The modified fibroblasts will be injected with a number of leukemic cells under the skin. All the cells will be irradiated before injection to stop them growing. Patients will receive three shots. Depending on the response, patients may be able to have three additional shots.
In order to collect the skin fibroblasts at the very beginning of the study, and then during the study, we will perform small skin biopsies. In particular before the second shot, and then again about 1 week later, we will look for both the modified and leukemia cells that have been re-injected under the skin. We will do this by taking a skin biopsy from the place where the cells were injected. The area where the skin biopsy will be obtained will be sterilized and then numbed with a local acting agent. The skin will be removed with a "tissue punch" which will cut a circle of approximately 1/4th of an inch into the skin. The site where the skin was removed will be closed with suture, tape or stitches. The area will be covered with dry gauze and adhesive tape. These tests are to see whether the shots are killing leukemia cells and to make sure leukemia cells are not growing at the injection site.
To study how the immunity is working in the system, we will take blood samples before 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 samples will be approximately 1 tablespoons of blood, 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.
Also, patients will need to have a bone marrow test before enrolling on the study and at week 12. If the patient is not responding, they may have treatment with other chemotherapy or radiation. Patients will need to come to the clinic on the days of blood drawing and to be seen at Texas Children's Cancer Center/The Methodist Hospital at weekly intervals for 10 weeks, then every other week for 6 weeks, and then monthly for a year. Thereafter, patients will either be seen in the clinic or contacted by one of the research staff working on this study once a year for 15 years. Additional visits may be necessary.
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 are treated with up to six injections of their gene-modified CD40L and IL-2 skin fibroblasts and leukemic blasts, separated by one-two weeks in an immunological treatment window. |
| Dose Level 2 | Experimental | Biological: Dose Level 2Patients are treated with up to six injections of their gene-modified CD40L and IL-2 skin fibroblasts and leukemic blasts, separated by one-two weeks in an immunological treatment window. |
| Dose Level 3 | Experimental | Biological: Dose Level 3Patients are treated with up to six injections of their gene-modified CD40L and IL-2 skin fibroblasts and leukemic blasts, separated by one-two weeks in an immunological treatment window. |
Who may qualify
- Ages
- Up to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Patients less than or equal to 75 years old with lymphoid (pre-B, B, T, non B-, non T, or Burkitt if bone marrow blasts > 20%) or acute myeloid leukemia (M0 to M7) or myelodysplastic syndrome and with: Disease that has entered remission with chemotherapy and/or bone marrow transplantation, but is considered to be at high risk of relapse. or Primary, or relapsed treatment-refractory disease who, at the time of reinjection of the tumor vaccine, are at a state of complete or partial cytological remission disease (<20% blasts infiltrating the bone marrow) after a second/higher line of conventional and/or high dose chemotherapy.
- Patients must have a life expectancy of at least 10 weeks.
- Patients must have ECOG performance status of 0-2 as below:
- Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study, and have an absolute neutrophil count >500/mm3, absolute lymphocyte count >200/mm3, and platelet count >50,000/mm3.
- Patients must not have active GvHD at the time of protocol entry.
Key exclusion criteria (6 listed)
- Rapidly progressive/refractory disease (>20% blasts infiltrating the bone marrow)
- Life expectancy < 10 weeks
- Active infection
- Need for concomitant drugs except analgesics
- Pregnancy or lactation
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 1Leukemic Blasts 2 x 10^7; IL-2 Fibroblasts 2 x 10^7; CD40L Fibroblasts 2 x 10^5 | Biological | Dose Level 1 |
| Dose Level 2Leukemic Blasts 2 x 10^7; IL-2 Fibroblasts 2 x 10^7; CD40L Fibroblasts 2 x 10^5 | Biological | Dose Level 2 |
| Dose Level 3Leukemic Blasts 2 x 10^7; IL-2 Fibroblasts 2 x 10^7; CD40L Fibroblasts 4.2 x 10^7 | Biological | Dose Level 3 |
Primary outcome
• To determine the safety of up to six subcutaneous (SC) injections of autologous tumor cells admixed with autologous gene-modified skin fibroblasts. These fibroblasts are modified ex vivo to express the human CD40 Ligand (hCD40L) and interleukin-2 (hIL
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, PhD principal investigator
Baylor College of Medicine
3 sites 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 3 in people with Leukemia, run by Baylor College of Medicine at 3 sites 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 13 inclusion and 6 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 3 sites 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?
• To determine the safety of up to six subcutaneous (SC) injections of autologous tumor cells admixed with autologous gene-modified skin fibroblasts. These fibroblasts are modified ex vivo to express the human CD40 Ligand (hCD40L) and interleukin-2 (hIL (time frame: 15 years). 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.