Hodgkins LymphomaPhase 1pediTACTALNCT05134740
(TAA)-Specific Cytotoxic T-Lymphocytes to Pediatric Patients With Lymphomas (pediTACTAL).
A Phase 1 study testing TAA-specific CTLs in people with Hodgkins Lymphoma and Non Hodgkins Lymphoma, run by Baylor College of Medicine at 1 site in United States.
Trial summary
Investigators have previously used this sort of therapy to treat Hodgkin or non-Hodgkin lymphoma that is associated with the virus that causes infectious mononucleosis ("mono" or the "kissing disease"), Epstein-Barr virus (EBV). Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Hodgkins Lymphoma, Non Hodgkins Lymphoma
- What is being tested?
- TAA-specific CTLs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2024to 1 Feb 2030
- 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 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Procurement Inclusion Criteria:
- Any pediatric patient (age ≥ 1 year and ≤ 21 years), regardless of sex, with a diagnosis of Hodgkin or non-Hodgkin Lymphoma.
- Patients with life expectancy > 6 weeks.
- Hgb ≥ 7.0 (transfusions allowed).
- Informed Consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. If applicable, patient assents to procurement,
Procurement Exclusion Criteria:
- Patients with severe intercurrent infection.
- Patients with active HIV, Hepatitis B, or Hepatitis C infection at time of procurement (can be pending at the time of blood draw).
- Patients receiving systemic corticosteroids at the time of or within one week prior to procurement.
- Presence of grade 2-4 acute GVHD or active chronic GVHD > mild global severity score.
Treatment Inclusion Criteria:
- Any pediatric patient (age ≥ 1 year and ≤ 21 years), regardless of sex, with a diagnosis of Hodgkin or non-Hodgkin Lymphoma who are in complete remission (CR), but at high risk for relapse (specifically, who are stage 3 or stage 4 at diagnosis, are in second complete remission (CR2), and who have previously received >2 lines of lymphoma-directed therapy).
- Pulse oximetry of > 90% on room air in patients who previously received radiation therapy.
- Patients with a Karnofsky/Lansky score of > 60
- Patients with bilirubin < 3x upper limit of normal
- Patients with a creatinine ≤ 2x upper limit of normal for age.
- Patients with AST < 3x upper limit of normal.
- Patients with Hgb ≥ 7.0 (transfusions allowed)
- Acceptable organ function based on clinical or laboratory findings according to investigator discretion
- Patients should have been off other investigational therapy for one month prior to entry in this study.
- Patients should have been off conventional therapy including rituximab for at least 1 week prior to entry in this study, and at least 4 weeks since last dose of radiation (if applicable)
- Informed Consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. If applicable, patient assents to participation in trial.
- Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. The male partner should use a condom. Females of child-bearing potential must be willing to utilize one of the more effective birth control methods during the study unless female has had a hysterectomy or tubal ligation
Treatment Exclusion Criteria:
- Patients with severe intercurrent infection.
- Presence of grade 2-4 acute GVHD or active chronic GVHD > mild global severity score.
- Patients receiving systemic corticosteroids > 0.5mg/kg prednisone or equivalent.
- Pregnant or breastfeeding.
- Active viral infection with HIV or hepatitis type B or C. "Active" infection defined as infectious disease testing indicating that patient blood is reactive for Hep B, C and/or HIV and confirmed using PCR to measure viral load.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Administration of Tumor-Associated Antigen (TAA)-Specific Cytotoxic T-Lymphocytes to Pediatric Patients With Lymphomas (pediTACTAL)
Investigators have previously used this sort of therapy to treat Hodgkin or non-Hodgkin lymphoma that is associated with the virus that causes infectious mononucleosis ("mono" or the "kissing disease"), Epstein-Barr virus (EBV). EBV is found in cancer cells of up to half of all patients with Hodgkin's and non-Hodgkin lymphoma. This suggests that it may play a role in causing lymphoma. The cancer cells infected by EBV are able to hide from the body's immune system and escape being killed. Investigators previously tested special white blood cells (cells that help the body fight disease and infection), called T cells. The T cells were trained to kill EBV-infected cells and were tested to see whether treatment with these cells could affect these tumors. In many patients investigators found that giving these trained T cells caused a complete or partial response.
However, many patients do not have EBV found in their lymphoma cells. Therefore, investigators now want to test whether special T lymphocytes directed against other types of proteins that show on the tumor cell surface can result in similar promising results. The proteins that will be targeted in this study are called tumor-associated antigens (TAAs) - these are cell proteins that are specific to the cancer cell, so they either do not show or show up in low quantities on normal human cells.
Read more
In this stage of the study, investigators will target five TAAs which commonly show on lymphoma cells , called NY-ESO-1, MAGEA4, PRAME, Survivin and SSX. Investigators will do this by using special types of T cells called cytotoxic T lymphocytes (CTLs) generated in the lab. These TM-specific T cells are an investigational product not yet approved by the U.S. Food and Drug Administration.
The purpose of this stage of the study is to find out if TM-specific cytotoxic T cells are safe in children. The investigators want to learn what the side-effects are, and to see whether this therapy might help treat patients who are considered high risk for relapse of Hodgkin disease or non-Hodgkin lymphoma.
Read the detailed description
First, patients provide blood for us to make TAA-specific cytotoxic T cells in the lab. The amount of blood to be drawn will be less based on the child's weight per blood draw (3 mL/kg). Under certain conditions related to the patient's health, investigators may need to collect the blood using a process called apheresis. Apheresis is the process where blood is passed through a machine that separates out the components of the patient's blood that is needed. The remainder of the patient's blood is then returned to the patient's body.
If the TAA-specific cytotoxic T cells can be made, the time from collection of the blood to manufacture of T cells for administration to the patient is about 1 to 2 months.
The cells will then be injected by IV into the patient over 10 minutes. The patient may be pre-treated with acetaminophen (Tylenol) and diphenhydramine (Benadryl). Acetaminophen (Tylenol) and diphenhydramine (Benadryl) are given to prevent a possible allergic reaction to the T cell administration. Initially, two doses of T cells will be given two weeks apart. The patient's lymphoma will be assessed before the infusion (pre-infusion) and then 6 weeks after the second infusion. If after the patient's second infusion he/she has not relapsed or experienced a side effect which would prevent him/her from receiving any more cells, he/she can receive up to six (6) additional doses if they wish. The T cells would then be given at 6-8 week intervals.
In between the first and second T cell infusions and for 6 weeks after the last infusion, investigators ask that the patient not receive any other anti-cancer treatments such as radiation therapy or chemotherapy. If the patient does receive any other therapies in-between the first and second infusion of T cells, they will be taken off treatment and will not be able to receive the second infusion of T cells. All of the treatments will be given by the Center for Cell and Gene Therapy at Texas Children 's Hospital.
MEDICAL TESTS BEFORE TREATMENT
Before being treated,the patient will receive a series of standard medical tests:
- Physical exam.
- Blood tests to measure blood cells, kidney and liver function.
- Measurements by routine imaging studies to confirm the patient is in remission. Investigators will use the imaging study that was used before to follow the patient's tumor: CT, MRI, or PET.
- Pregnancy test if the patient is a female who can have children.
MEDICAL TESTS AFTER TREATMENT
- Imaging study 8 weeks after the 2nd TAA-CTL infusion.
To learn more about the way the T cells are working in the patient's body , an extra 20-40 ml (4-8 teaspoons) of blood or 3ml/kg of body weight of blood (whichever is less) will be taken before the infusion, and at weeks 2, 4 and 8. Afterwards, blood will be collected at 3, 6, 9 and 12 months after the last infusion. The blood may be drawn from the patient's central line at the time of his or her regular blood tests. Investigators will use this blood to see how long the T cells last, and to look at the patient's immune response to their cancer.
If the patient receives additional doses of T cells this blood will also be collected before each infusion and 1, 2, 4, and 6 weeks post each infusion.
The maximum amount of blood that may be drawn over the course of the study is 156 to 312 teaspoon.
Investigators may request a sample of a previous tumor biopsy the patient has had or from a tumor biopsy performed at any time while the patient is on this study. The sample will be used for research purposes related to this study.
In the event of death, investigators will request permission to perform an autopsy to learn more about the effects of the treatment on the patient's disease.
STUDY DURATION The patient's active participation in this study will last for approximately one 1 year. If they receive additional doses of the T cells as described above, their active participation will last until one 1 year after their last dose of T cells. Investigators will then contact them once a year for up to 4 additional years (total of 5 years follow-up) in order to evaluate their disease response long-term.
- Conditions
- Hodgkins Lymphoma, Non Hodgkins Lymphoma
- Being tested
- TAA-specific CTLs
- Keywords
- Hodgkins Lymphoma, Non Hodgkins Lymphoma, TAA, TAA specific T lymphocytes, Hodgkins Lymphona high risk for relapse, Non-Hodgkin's Lymphoma high risk for relapse, pediatric Hodgkin's Lymphoma high risk, pediatric non-Hodgkin's Lymphoma high risk
- Medical subject headings
- Hodgkin Disease, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAA-specific CTLsBiological
Each patient will receive 2 infusions at the same dose, 14 days apart, according to the following dose level:
2 x 10^7/m2
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm | Experimental | Patients receiving autologous TAA-specific cytotoxic CTLs Receives: Biological: TAA-specific CTLs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-related adverse event (tAE) Rate
Treatment-related adverse event (tAE) rate is the proportion of participants with tAE measured by the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The tAE will be defined as development of Grade III-IV events in any organ system that do not return to grade I within 72 hours with the exception of events that are clearly unrelated, and, of hematological toxicities, which are only considered a tAE if Grade III persisting for up to 10 days or greater than or equal to Grade IV. In addition grade 2 or greater autoimmune reaction will be considered a tAE.
Measured: 8 weeks post first CTL infusion
Secondary outcomes (1)
Obtain information on the expansion, persistence and anti-tumor effects of the adoptively-transferred TAA-specific CTLs
Information on the expansion, persistence and anti-tumor effects of the adoptively transferred tumor-specific CTL will be analyzed for the immunological parameters based on multimer analysis, intracellular cytokine staining and ELIspot assays to assess the frequency of cells secreting γ-IFN using the descriptive statistics such as mean, median, standard deviation at each time point. Comparison of diagnostic imaging studies from pre-infusion to 6 weeks following the second infusion will be summarized
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2021
- Study startApr 2024 (estimated)
- Primary completion24 Feb 2025 (estimated)
- Study completion1 Feb 2030 (estimated)
Why it stopped: Leadership determination
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hodgkins LymphomaStudies 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Center for Cell and Gene Therapy, Baylor College of Medicine
- Responsible party
- Principal investigator, Lauren Scherer, Baylor College of Medicine
- Investigators
- Lauren Scherer, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05134740
- Sponsor's protocol ID
- H-49884 (pediTACTAL)
- Acronym
- pediTACTAL
- Status last verified
- Oct 2024
- First submitted
- 15 Nov 2021
- Last updated
- 22 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administration of Tumor-Associated Antigen (TAA)-Specific Cytotoxic T-Lymphocytes to Pediatric Patients With Lymphomas (pediTACTAL)
- ClinicalTrials.gov ID
- NCT05134740
- Acronym / sponsor ID
- pediTACTAL / H-49884 (pediTACTAL)
- Conditions
- Hodgkins Lymphoma, Non Hodgkins Lymphoma
- Keywords
- Hodgkins Lymphoma, Non Hodgkins Lymphoma, TAA, TAA specific T lymphocytes, Hodgkins Lymphona high risk for relapse, Non-Hodgkin's Lymphoma high risk for relapse, pediatric Hodgkin's Lymphoma high risk, pediatric non-Hodgkin's Lymphoma high risk
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Leadership determination
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- Center for Cell and Gene Therapy, Baylor College of Medicine
- Study start
- Apr 2024 (estimated)
- Primary completion
- 24 Feb 2025 (estimated)
- Study completion
- 1 Feb 2030 (estimated)
- First posted
- 26 Nov 2021 (actual)
- 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.
Investigators have previously used this sort of therapy to treat Hodgkin or non-Hodgkin lymphoma that is associated with the virus that causes infectious mononucleosis ("mono" or the "kissing disease"), Epstein-Barr virus (EBV). EBV is found in cancer cells of up to half of all patients with Hodgkin's and non-Hodgkin lymphoma. This suggests that it may play a role in causing lymphoma. The cancer cells infected by EBV are able to hide from the body's immune system and escape being killed. Investigators previously tested special white blood cells (cells that help the body fight disease and infection), called T cells. The T cells were trained to kill EBV-infected cells and were tested to see whether treatment with these cells could affect these tumors. In many patients investigators found that giving these trained T cells caused a complete or partial response.
However, many patients do not have EBV found in their lymphoma cells. Therefore, investigators now want to test whether special T lymphocytes directed against other types of proteins that show on the tumor cell surface can result in similar promising results. The proteins that will be targeted in this study are called tumor-associated antigens (TAAs) - these are cell proteins that are specific to the cancer cell, so they either do not show or show up in low quantities on normal human cells.
In this stage of the study, investigators will target five TAAs which commonly show on lymphoma cells , called NY-ESO-1, MAGEA4, PRAME, Survivin and SSX. Investigators will do this by using special types of T cells called cytotoxic T lymphocytes (CTLs) generated in the lab. These TM-specific T cells are an investigational product not yet approved by the U.S. Food and Drug Administration.
The purpose of this stage of the study is to find out if TM-specific cytotoxic T cells are safe in children. The investigators want to learn what the side-effects are, and to see whether this therapy might help treat patients who are considered high risk for relapse of Hodgkin disease or non-Hodgkin lymphoma.
Detailed description
First, patients provide blood for us to make TAA-specific cytotoxic T cells in the lab. The amount of blood to be drawn will be less based on the child's weight per blood draw (3 mL/kg). Under certain conditions related to the patient's health, investigators may need to collect the blood using a process called apheresis. Apheresis is the process where blood is passed through a machine that separates out the components of the patient's blood that is needed. The remainder of the patient's blood is then returned to the patient's body.
If the TAA-specific cytotoxic T cells can be made, the time from collection of the blood to manufacture of T cells for administration to the patient is about 1 to 2 months.
The cells will then be injected by IV into the patient over 10 minutes. The patient may be pre-treated with acetaminophen (Tylenol) and diphenhydramine (Benadryl). Acetaminophen (Tylenol) and diphenhydramine (Benadryl) are given to prevent a possible allergic reaction to the T cell administration. Initially, two doses of T cells will be given two weeks apart. The patient's lymphoma will be assessed before the infusion (pre-infusion) and then 6 weeks after the second infusion. If after the patient's second infusion he/she has not relapsed or experienced a side effect which would prevent him/her from receiving any more cells, he/she can receive up to six (6) additional doses if they wish. The T cells would then be given at 6-8 week intervals.
In between the first and second T cell infusions and for 6 weeks after the last infusion, investigators ask that the patient not receive any other anti-cancer treatments such as radiation therapy or chemotherapy. If the patient does receive any other therapies in-between the first and second infusion of T cells, they will be taken off treatment and will not be able to receive the second infusion of T cells. All of the treatments will be given by the Center for Cell and Gene Therapy at Texas Children 's Hospital.
MEDICAL TESTS BEFORE TREATMENT
Before being treated,the patient will receive a series of standard medical tests:
- Physical exam.
- Blood tests to measure blood cells, kidney and liver function.
- Measurements by routine imaging studies to confirm the patient is in remission. Investigators will use the imaging study that was used before to follow the patient's tumor: CT, MRI, or PET.
- Pregnancy test if the patient is a female who can have children.
MEDICAL TESTS AFTER TREATMENT
- Imaging study 8 weeks after the 2nd TAA-CTL infusion.
To learn more about the way the T cells are working in the patient's body , an extra 20-40 ml (4-8 teaspoons) of blood or 3ml/kg of body weight of blood (whichever is less) will be taken before the infusion, and at weeks 2, 4 and 8. Afterwards, blood will be collected at 3, 6, 9 and 12 months after the last infusion. The blood may be drawn from the patient's central line at the time of his or her regular blood tests. Investigators will use this blood to see how long the T cells last, and to look at the patient's immune response to their cancer.
If the patient receives additional doses of T cells this blood will also be collected before each infusion and 1, 2, 4, and 6 weeks post each infusion.
The maximum amount of blood that may be drawn over the course of the study is 156 to 312 teaspoon.
Investigators may request a sample of a previous tumor biopsy the patient has had or from a tumor biopsy performed at any time while the patient is on this study. The sample will be used for research purposes related to this study.
In the event of death, investigators will request permission to perform an autopsy to learn more about the effects of the treatment on the patient's disease.
STUDY DURATION The patient's active participation in this study will last for approximately one 1 year. If they receive additional doses of the T cells as described above, their active participation will last until one 1 year after their last dose of T cells. Investigators will then contact them once a year for up to 4 additional years (total of 5 years follow-up) in order to evaluate their disease response long-term.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm | Experimental | Biological: TAA-specific CTLsPatients receiving autologous TAA-specific cytotoxic CTLs |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
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 |
|---|---|---|
| TAA-specific CTLsEach patient will receive 2 infusions at the same dose, 14 days apart, according to the following dose level: 2 x 10^7/m2 | Biological | Experimental Arm |
Primary outcome
Treatment-related adverse event (tAE) Rate
Time frame: 8 weeks post first CTL infusion
Treatment-related adverse event (tAE) rate is the proportion of participants with tAE measured by the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The tAE will be defined as development of Grade III-IV events in any organ system that do not return to grade I within 72 hours with the exception of events that are clearly unrelated, and, of hematological toxicities, which are only considered a tAE if Grade III persisting for up to 10 days or greater than or equal to Grade IV. In addition grade 2 or greater autoimmune reaction will be considered a tAE.
1 secondary outcome
Obtain information on the expansion, persistence and anti-tumor effects of the adoptively-transferred TAA-specific CTLs
Time frame: 8 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2024.
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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.
Lauren Scherer, MD principal investigator
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 TAA-specific CTLs in people with Hodgkins Lymphoma and Non Hodgkins Lymphoma, 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?
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: withdrawn, as of the sponsor's last update on 22 Oct 2024. 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 was withdrawn before enrolling participants, so there are no results.
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?
Treatment-related adverse event (tAE) Rate (time frame: 8 weeks post first CTL infusion). 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 22 Oct 2024.