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....
Diagnosis
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
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
9
Treatment groupsSee each treatment group below.