At a glance
ClinicalIndex Comparison Record- ✓Pathology-confirmed B-cell ALL (not isolated to testis or CNS), CML with ALL transformation, or high-grade lymphoma (Burkitt's, B-lymphoblastic, DLBCL, or transformed low-grade disease)
- ✓Relapsed or refractory after at least one standard chemotherapy regimen and at least one salvage treatment; Ph+ ALL must have failed prior tyrosine kinase inhibitor
- ✓Ineligible for allogeneic SCT, refused SCT, or recurred after SCT
- ✓Unable to access, ineligible for, or relapsed/failed after commercially available CD19 CAR-T construct
- ✕CNS3 disease or progressing neurologic signs of CNS disease or radiologically active CNS lymphoma
- ✕Hyperleukocytosis (≥50,000 blasts/microL)
- ✕Positive serum or urine beta-HCG pregnancy test at screening
- ✕Positive HIV antibodies consistent with active HIV
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
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
In Brief
A Phase 1 clinical trial evaluating CD19/CD22-CAR-transduced T cells, cyclophosphamide, and 1 other intervention for B-NHL and 10 related conditions. Currently recruiting, targeting 130 participants across 1 site.
Detailed 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....
Study Details
Timeline
Arms & Interventions
CD19/CD22-CAR-transduced T cells at escalating dose + standard LD (75 mg/mg2 Flu+ 900 mg/m2 Cy)
CD19/CD22-CAR-transduced T cells
CD19/CD22-CAR-transduced T cells + standard LD (120 mg/m2 Flu + 1200 mg/m2 Cy)
CD19/CD22-CAR-transduced T cells
CD19/CD22-CAR-transduced T cells at MTD/or highest dose administered with LD
CD19/CD22-CAR-transduced T cells
CD19/CD22-CAR-transduced T cells at MTD/or highest dose administered with LD regimen #2
CD19/CD22-CAR-transduced T cells at RP2D
All participants enrolled on the study prior to treatment initiation.
Interventions
CD19/CD22-CAR-transduced T cells on D0 after lymphodepleting preparative regimen
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 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).