Recruiting
Phase 1
Phase 2

CAR T Cells

Sponsor:

National Cancer Institute (NCI)

Code:

NCT05442515

Conditions

B-NHL

B-Non Hodgkin Lymphoma

Acute Lymphocytic Leukemia

Acute Lymphoblastic Leukemia

B-precursor ALL

Eligibility Criteria

Sex: All

Age: 3 - 39

Healthy Volunteers: Not accepted

Interventions

CD19/CD22-CAR-transduced T cells

cyclophosphamide

fludarabine

Study Details

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....

Conditions

B-NHL

B-Non Hodgkin Lymphoma

Acute Lymphocytic Leukemia

Acute Lymphoblastic Leukemia

B-precursor ALL

Study ID

NCT05442515

Start date

Dec 28, 2022

Status verified date

Jul 28, 2026

Completion date

Jul 1, 2029

Anticipated

Primary completion date

Jul 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 3 - 39

Healthy Volunteers: Not accepted

  • 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.

Study Design

Enrollment

130 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 1/Phase I Dose Escalation-with standard LD - CLOSED

CD19/CD22-CAR-transduced T cells at escalating dose + standard LD (75 mg/mg2 Flu+ 900 mg/m2 Cy)

experimental: 1b/Phase 1 Dose Escalation - low disease burden

CD19/CD22-CAR-transduced T cells

experimental: 2/Phase I Dose Escalation- with intensified LD - CLOSED

CD19/CD22-CAR-transduced T cells + standard LD (120 mg/m2 Flu + 1200 mg/m2 Cy)

experimental: 2b/Phase 1 Dose Escalation - high disease burden

CD19/CD22-CAR-transduced T cells

experimental: 3/Phase II Dose Expansion- with low disease burden - CLOSED

CD19/CD22-CAR-transduced T cells at MTD/or highest dose administered with LD

experimental: 3b Phase I Dose Escalation: Either CD19 or CD22 positivity

CD19/CD22-CAR-transduced T cells

experimental: 4/Phase II Dose Expansion- with high disease burden - CLOSED

CD19/CD22-CAR-transduced T cells at MTD/or highest dose administered with LD regimen #2

experimental: 4b Phase II Dose Expansion in B-ALL/B-LBL

CD19/CD22-CAR-transduced T cells at RP2D

no intervention: A/Pre-treatment

All participants enrolled on the study prior to treatment initiation.

Interventions

CD19/CD22-CAR-transduced T cells

CD19/CD22-CAR-transduced T cells on D0 after lymphodepleting preparative regimen

cyclophosphamide

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

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).

Primary outcome measure

  • Safety [ Time Frame: 30 days post CAR T infusion ]
  • Efficacy [ Time Frame: 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. ]

Central Contacts and Locations

Central contacts

NCI Ped LeukemiaLymph Cell Tx Tm

(240) 760-6970ncilltct@mail.nih.gov

Sara K Silbert, M.D.

(240) 858-3666sara.silbert@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

888-624-1937

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Jul 30, 2026

Last verified

Jul 28, 2026

Keywords

  • Philadelphia chromosome + ALL
  • Lymphoma
  • CD-22 Expressing Tumor
  • CD-19 expressing tumor
  • Adoptive Immunotherapy
  • B-All
  • B-precursor ALL
  • Acute Lymphoblastic Leukemia
  • Acute Lymphocytic Leukemia
  • B-Non Hodgkin Lymphoma

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-07-30.