Tests modified immune cells in young people with returning or resistant B-cell leukemia

Trial details

Who runs it

National Cancer Institute (NCI)

Trial code

NCT05442515

Record updated

26 October 2026

Original description

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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

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....

Exclusion: 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); 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; Positive HIV antibodies consistent with active HIV; Positive hepatitis C antibodies or positive Hepatitis B surface antigen (HbsAG) indicative of current/active HCV/HBV; 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; 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; Participants meeting any of the following criteria are not eligible for participation in the study:; Hyperleukocytosis (>= 50,000 blasts/microL).

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.

ClinicalTrials.gov NCT05442515