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CD19/CD22 Bicistronic Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory 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 B Cell Malignancies
Who can join
Ages 3 to 39 · All sexes
Full eligibility criteria
* INCLUSION CRITERIA:
* 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
* 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
* Cohorts A1b, B1b, C2b
* CD19 must be detected on \>15% of the malignant cells by immunohistochemistry or \> 80% by flow cytometry.
* CD22 positivity must be confirmed.
* Cohorts D1b, 2 B-ALL
* CD19 or 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\*
* platelets \>= 50,000/mcL\*
* total bilirubin \<=2 X ULN (except in the case of participants with documented Gilbert's disease \> 3x ULN)
* AST(SGOT)/ALT(SGPT) \<=10 X institutional upper limit of normal
* creatinine \<= the maximum for age listed in the table below OR
* measured creatinine clearance \>=60 mL/min/1.73 m\^2 for participants with creatinine levels above the max listed below per age.
* Age (Years) \<= 5 / Maximum Serum Creatinine (mg/dL) \<= 0.8
* Age (Years) 6 to \<= 10 / Maximum Serum Creatinine (mg/dL) \<= 1.0
* Age (Years) \>10 / Maximum Serum Creatinine (mg/dL) \<= 1.2
* a participant will not be excluded because of pancytopenia \>= Grade 3 if it is due to underlying bone marrow involvement by leukemia
* Central nervous system (CNS) Status
* Participants with leukemia with CNS 1 and 2 disease are eligible in the absence of exclusion criteria
* 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.
EXCLUSION CRITERIA:
Participants meeting any of the following criteria are not eligible for participation in the study:
* Participants with CNS3 disease, progressing neurologic signs\* of CNS disease, radiologically detected active CNS lymphoma (\*resolving manifestation or persistent and/or irreversible findings from prior CNS involvement (e.g., blindness) is not exclusionary)
* 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
* Washout\*: \>=3 weeks
* Exceptions: No time restriction with radiation therapy if the volume of bone marrow treated is less than 10% and the participant has measurable/evaluable disease outside the radiation window
* Therapy: Allogeneic Stem Cell Transplant
* Washout\*: \>= 100 days since SCT; \>= 30 days since completion of immunosuppression; \>= 6 weeks since donor lymphocyte infusion (DLI)
* Exceptions: Cannot have evidence of active graft-versus-host disease (GVHD) requiring systemic immunosuppression
* Therapy: CAR T-Cell Therapy or other Adoptive Cell Therapy
* Washout\*: \> 30 days post infusion
* Washout: Time between therapy and apheresis
* Positive HIV antibodies consistent with active HIV.
* Positive hepatitis C antibodies or positive Hepatitis B surface antigen (HbsAG) indicative of current/active HCV/HBV.
* Active second malignancy other than in situ carcinoma of the cervix, unless the tumor was treated with curative intent at least two years previously and participant is in remission.
* History of severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in study or in the manufacturing of the cells.
* Uncontrolled, symptomatic, intercurrent illness or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the participant.About the study
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....
What is being tested
- CD19/CD22-CAR-transduced T cells (biological)
- cyclophosphamide (drug)
- fludarabine (drug)
Sponsor: National Cancer Institute (NCI) · Participants: 130 · Started: Dec 28, 2022
Contact the study team
- NCI Ped LeukemiaLymph Cell Tx Tm · Phone: (240) 760-6970
- Sara K Silbert, M.D. · Phone: (240) 858-3666
Official record on ClinicalTrials.gov — NCT05442515
Locations in the U.S.
| Maryland | National Institutes of Health Clinical Center, Bethesda |
Conditions
- Acute Lymphoblastic Leukemia
- Burkitt Lymphoma
- Non-Hodgkin Lymphoma
- B-Cell Leukemia
- B-Cell Lymphoma
- Lymphoma
From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.