Overview

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....

Eligibility

• 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
    • 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\
  • 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)
  • 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.