CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies
Lymphoma, Non-Hodgkin · Leukemia, Lymphocytic, B Cell · B-Cell Lymphoma · B-Cell Leukemia · Acute Lymphoid Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT03448393 ↗Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- CD19/CD22 CAR T-Cells (Biological); Fludarabine (Drug); Cyclophosphamide (Drug); Apheresis (Procedure); Anti-emetic (Other); Diphenhydramine (Drug); Acetaminophen (Drug); ECG (Diagnostic_test); ECHO (Diagnostic_test); MRI Brain (Diagnostic_test); Bone marrow biopsy (Procedure); Cardiac MRI (Diagnostic_test)
- Age
- Pediatric, Adult · 3+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Jul 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Grades of Toxicity by Type of Toxicity |
2; 2; 1; 1; 1; 13 | — |
| PRIMARY Maximum Tolerated Dose (MTD) |
3 | — |
| SECONDARY Number of Participants That Have Successful Manufacture of the Targeted Dose Number of Chimeric Antigen Receptor (CAR) Cells |
4; 4; 5; 2; 1; 21 | — |
| SECONDARY Overall Survival |
12.2; 17.8; 45.4; 15.3; 60; 20.7 | — |
| SECONDARY Progression-free Survival (PFS) |
6.4; 2.6; 20.1; 5.3; 60; 14.2 | — |
| SECONDARY Clinical Activity (Response) in Children and Young Adults With B-cell Acute Lymphoblastic Leukemia (B-ALL), Isolated Central Nervous System (CNS) ALL, or Lymphoma Who Previously Received Chimeric Antigen Receptor (CAR) Therapy and Those That Are CAR Naive |
50; 100; 90.5; 100; 100; 50 | — |
Summary
Eligibility Criteria
- ELIGIBILITY CRITERIA:
Study subjects with cluster of differentiation 19 (CD19) + cluster of differentiation 22 (CD22+) expressing B cell malignancies who have relapsed or are treatment refractory may enroll as defined by the following inclusion and exclusion criteria.
INCLUSION CRITERIA
- Diagnosis
- Participant must have a B cell acute lymphoblastic leukemia (ALL) (inclusive of chronic myeloid leukemia (CML) with ALL transformation) or lymphoma and must have relapsed or refractory disease after at least one standard chemotherapy regimen and one salvage regimen. In view of the principal investigator (PI) and the primary oncologist, there must be no available alternative curative therapies and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, recurred after SCT, or have disease activity that prohibits SCT at the time of enrollment. Participants who have undergone autologous SCT will be eligible, and participants that have undergone allogeneic SCT will be eligible if, in addition to meeting other eligibility criteria, they have no evidence of graft versus host disease (GVHD) and have been without immunosuppressive agents for at least 30 days. Participants with Philadelphia chromosome + ALL must have failed prior tyrosine kinase inhibitor.
- Participants must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis. For those being considered for reinfusions, measurable or evaluable disease is not required at the time of reinfusion.
- CD22/CD19 expression
--CD19 expression must be detected on greater than 15% of the malignant cells by immunohistochemistry or greater than 90% by flow cytometry. The choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each participant. In general, immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples. CD22+ B cell malignancy is required and CD22 expression levels will be documented when available, but a specific level of expression is not an eligibility requirement; it may be documented as positive or negative.
- Age:
--Greater than or equal to 3 years of age (and at least 15 kg) and less than or equal to 39 years of age at time of enrollment (greater than or equal to 3 years to less than or equal to 39 years). NOTE: The first participant in each dose cohort must be greater than or equal to 18 years of age.
- Clinical Performance
--Clinical performance status: Participants greater than or equal to 16 years of age: Karnofsky greater than or equal to 50%; Participants 3x ULN)
- Aspartate aminotransferase (AST)serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT)serum glutamate pyruvate transaminase (SGPT) less than or equal to 10 X institutional upper limit of normal
- creatinine less than or equal to the maximum for age listed in the table below
- Age (Years): less than or equal to 5. Maximum Serum Creatinine (mg/dL): less than or equal to 0.8
- Age (Years): 6 to less than or equal to 10. Maximum Serum Creatinine (mg/dL): less than or equal to 1.0
- Age (Years): >10. Maximum Serum Creatinine (mg/dL): less than or equal to 1.2
- OR
- creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal.
- if these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy); A subject will not be excluded because of pancytopenia greater than or equal to Grade 3 if it is due to disease, based on the results of bone marrow studies.
- Subjects with central nervous system (CNS) disease are eligible, with exceptions as noted in the exclusion criteria
- Contraceptio
Data sourced from ClinicalTrials.gov (NCT03448393). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.