CD19/CD22 Bicistronic Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies
Phase 1/2 Dose Escalation Study of CD19/CD22 Bicistronic Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies
2 other identifiers
interventional
126
1 country
1
Brief Summary
Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. About 90% of children and young adults who are treated for ALL can now be cured. But if the disease comes back, the survival rate drops to less than 50%. Better treatments are needed for ALL relapses. Objective: To test chimeric antigen receptor (CAR) therapy. CARs are genetically modified cells created from each patient s own blood cells. his trial will use a new type of CAR T-cell that is targeting both CD19 and CD22 at the same time. CD19 and CD22 are proteins found on the surface of most types of ALL. Eligibility: People aged 3 to 39 with ALL or related B-cell lymphoma that has not been cured by standard therapy. Design: Participants will be screened. This will include: Physical exam Blood and urine tests Tests of their lung and heart function Imaging scans Bone marrow biopsy. A large needle will be inserted into the body to draw some tissues from the interior of a bone. Lumbar puncture. A needle will be inserted into the lower back to draw fluid from the area around the spinal cord. Participants will undergo apheresis. Their blood will circulate through a machine that separates blood into different parts. The portion containing T cells will be collected; the remaining cells and fluids will be returned to the body. The T cells will be changed in a laboratory to make them better at fighting cancer cells. Participants will receive chemotherapy starting 4 or 5 days before the CAR treatment. Participants will be admitted to the hospital. Their own modified T cells will be returned to their body. Participants will visit the clinic 2 times a week for 28 days after treatment. Follow-up will continue for 15 years....
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2022
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 1, 2022
CompletedFirst Posted
Study publicly available on registry
July 5, 2022
CompletedStudy Start
First participant enrolled
December 28, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2029
March 12, 2026
March 9, 2026
4.5 years
July 1, 2022
March 11, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Efficacy
Determine the efficacy of CD19/CD22 therapy in participants stratified by disease burden.
Monthly until 3 months post CAR T infusion and then at 6 months and every 6 months after that, for 2 years post-infusion for each participant, up to 2 years after the entry date of the last participant.
Safety
Assess the safety of administering escalating doses of autologous CD19/CD22-CAR engineered T cells in children and young adult with B cell ALL (stratified by disease burden) or lymphoma following a cyclophosphamide/fludarabine LD.
30 days post CAR T infusion
Secondary Outcomes (6)
Feasibility
Up to two years after the last participant has entered.
Adverse Events
30 days post CAR T infusion
Persistence and expansion
Up to two years after the last participant has entered.
Progression free survival (PFS) and Overall survival (OS)
Up to two years after the last participant has entered.
Overall response rate
Monthly until 3 months post infusion and then at 6 months and every 6 months after that, for 2 years post-infusion for each participant, for up to two years from the entry date of the last participant
- +1 more secondary outcomes
Study Arms (7)
1/Phase I Dose Escalation-with standard LD - CLOSED
EXPERIMENTALCD19/CD22-CAR-transduced T cells at escalating dose + standard LD
1b/Phase 1 Dose Escalation - low disease burden
EXPERIMENTALCD19/CD22-CAR-transduced T cells
2/Phase I Dose Escalation- with intensified LD - CLOSED
EXPERIMENTALCD19/CD22-CAR-transduced T cells + standard LD
2b/Phase 1 Dose Escalation - high disease burden
EXPERIMENTALCD19/CD22-CAR-transduced T cells
3/Phase II Dose Expansion- with low disease burden
EXPERIMENTALCD19/CD22-CAR-transduced T cells at MTD/or highest dose administered with LD
4/Phase II Dose Expansion- with high disease burden
EXPERIMENTALCD19/CD22-CAR-transduced T cells at MTD/or highest dose administered with LD regimen #2
A/Pre-treatment
NO INTERVENTIONAll participants enrolled on the study prior to treatment initiation.
Interventions
CD19/CD22-CAR-transduced T cells on D0 after lymphodepleting preparative regimen
Cyclophosphamide will be diluted in an appropriate solution and infused over one hour. The dose will be based on the patient s body weight, at 900 mg/m2/dose after fludarabine infusion.
Fludarabine is administered as an IV infusion in an appropriate solution over 30 minutes. To prevent undue toxicity the dose will be based on BSA (25 mg/m2/dose).
Eligibility Criteria
You may qualify if:
- Diagnosis
- Participant must:
- Have pathology confirmed B cell ALL (not isolated to the testis or CNS), CML with ALL transformation, or high-grade lymphoma (e.g., Burkitt's lymphoma, B-lymphoblastic lymphoma, diffuse large B-cell lymphoma, inclusive of low-grade lymphoma that has transformed to high grade disease); and
- Have relapsed or been refractory after at least one standard chemotherapy regimen and at least one salvage treatment. Participants with Philadelphia chromosome + ALL must have failed prior tyrosine kinase inhibitor; and
- Be ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have recurred after SCT; and
- Have no evidence of graft-versus- host disease (GVHD) and have been without immunosuppressive agents for at least 30 days prior to apheresis, if undergone prior allogeneic SCT; and
- Be unable to access (in a timely manner), ineligible for, or have relapsed/failed after or not responded to a commercially available CD19 CAR T-cell construct; and
- Have evidence of at least minimal residual disease or PET-avid disease (lymphoma) at the time of enrollment.
- CD22/CD19 expression
- CD19 must be detected on \>15% of the malignant cells by immunohistochemistry or \> 80% by flow cytometry.
- CD22 positivity must be confirmed.
- Age \>= 3 years of age and \<=39 years of age at time of enrollment.
- Clinical Performance status: Participants \>= 16 years of age: Karnofsky \>= 50%; Participants \< 16 years of age: Lansky scale \>= 50%.
- Participants must have adequate organ and marrow function as defined below:
- leukocytes \>= 750/mcL\*
- +10 more criteria
You may not qualify if:
- Participants of child-bearing or child-fathering potential must be willing to practice effective birth control from the time of enrollment until 12 months following completion of study treatment for women and for 4 months following completion of study treatment for men.
- Participants who are breastfeeding or plan to breastfeed must agree to discontinue/postpone breastfeeding while on study therapy and until 1 month after the administration of CAR.
- Cardiac function: Left ventricular ejection fraction \>= 45% or fractional shortening \>=28%
- Pulmonary Function
- Baseline oxygen saturation \>92% on room air at rest
- Ability of participant or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
- Ability and willingness of participant or Legally Authorized Representative (LAR) to co- enroll on 15-C-0028: Follow-up Evaluation for Gene-Therapy Related Delayed Adverse Events after Participation in Pediatric Oncology Branch Clinical Trials.
- Participants meeting any of the following criteria are not eligible for participation in the study:
- Hyperleukocytosis (\>= 50,000 blasts/microL)
- Positive serum or urine beta-HCG pregnancy test performed at screening.
- Participants will be excluded based on prior therapy if they fail to meet following washout criteria:
- Therapy: Systemic Chemotherapy, anti-neoplastic agents, antibody- based therapies
- Washout\*: \>=2 weeks
- Exceptions: 6 weeks for clofarabine or nitrosoureas; No washout for prior intrathecal chemotherapy, steroid therapy, hydroxyurea (no dose increases within prior 2 weeks) or ALL maintenance-type chemotherapy (vincristine, 6-mercaptopurine, oral methotrexate, or a tyrosine kinase inhibitor for participants with Ph+ ALL) provided there is recovery from any acute toxic effects
- Therapy: Radiation
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nirali N Shah, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 1, 2022
First Posted
July 5, 2022
Study Start
December 28, 2022
Primary Completion (Estimated)
July 1, 2027
Study Completion (Estimated)
July 1, 2029
Last Updated
March 12, 2026
Record last verified: 2026-03-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely.
- Access Criteria
- Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.
All IPD recorded in the medical record will be shared with intramural investigators upon request.