CD19/CD22 Bicistronic Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies

Launched by NATIONAL CANCER INSTITUTE (NCI) · Jul 1, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment for children and young adults with certain types of leukemia and lymphoma that have not responded to standard treatments. It uses a special therapy called CAR T-cell therapy, where a patient's own immune cells (T cells) are modified in a lab to better recognize and attack cancer cells. This particular trial focuses on T cells that target two proteins, CD19 and CD22, which are found on the surface of many cancer cells in these blood cancers.

To participate, patients must be between the ages of 3 and 39 and have a diagnosis of acute lymphoblastic leukemia (ALL) or related B-cell malignancies that have not been successfully treated with other therapies. The process includes several medical tests to ensure safety and effectiveness, and participants will receive chemotherapy before their modified T cells are given back to them in a hospital setting. After treatment, participants will need to visit the clinic regularly for monitoring. This trial aims to find better treatment options for those who have limited choices due to relapsed cancer.

Gender

ALL

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
• • 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, neurologic signs of CNS disease, radiologically detected active CNS lymphoma
• • 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.