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

ConditionsB-NHLB-Non Hodgkin LymphomaAcute Lymphocytic LeukemiaAcute Lymphoblastic LeukemiaB-precursor ALLB-AllLymphoma, Non-HodgkinLeukemia, Lymphocytic, B CellB-Cell LymphomaB-Cell LeukemiaAcute Lymphoid Leukemia
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age3-39
SponsorNational Cancer Institute (NCI)

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • CD19/CD22-CAR-transduced T cells

    Biological/Vaccine

    CD19/CD22-CAR-transduced T cells on D0 after lymphodepleting preparative regimen

  • cyclophosphamide

    Drug

    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

    Drug

    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).

Treatment groups

130 Participants
are divided into 9 treatment groups

9

Treatment groups

See each treatment group below.

Group A: 1/Phase I Dose Escalation-with standard LD - CLOSEDExperimental treatment 3 interventions
Group B: 1b/Phase 1 Dose Escalation - low disease burdenExperimental treatment 3 interventions
Group C: 2/Phase I Dose Escalation- with intensified LD - CLOSEDExperimental treatment 3 interventions
Group D: 2b/Phase 1 Dose Escalation - high disease burdenExperimental treatment 3 interventions
Group E: 3/Phase II Dose Expansion- with low disease burden - CLOSEDExperimental treatment 3 interventions
Group F: 3b Phase I Dose Escalation: Either CD19 or CD22 positivityExperimental treatment 3 interventions
Group G: 4/Phase II Dose Expansion- with high disease burden - CLOSEDExperimental treatment 3 interventions
Group H: 4b Phase II Dose Expansion in B-ALL/B-LBLExperimental treatment 3 interventions
Group I: A/Pre-treatmentNo intervention 0 interventions

Trial outcomes

Primary outcomes

1

Safety

Assess the safety of administering escalating doses of autologous CD19/CD22-CAR engineered T cells in children and young adult with B cell ALL or lymphoma following a cyclophosphamide/fludarabine LD.

Time frame
30 days post CAR T infusion
2

Efficacy

Determine the efficacy of CD19/CD22 therapy in participants with B-ALL/B-LBL.

Time frame
Monthly until 3 months post CAR T infusion and then at 6 months and every 6 months after that, for 2 years post-infusion for each participant, up to 2 years after the entry date of the last participant.

Secondary outcomes

1

Assess response and toxicity (CRS grade)

Assess overall response rate and CRS grades (toxicity) in participants who received subsequent infusion

Time frame
Up to two years after last participant has entered
2

Overall response rate

Phase I: Evaluate the ability of CD19/CD22-CAR T cells to mediate clinical activity in children and young adults with CD19+ and/or CD22+ B cell ALL or lymphoma.

Time frame
Monthly until 3 months post infusion and then at 6 months and every 6 months after that, for 2 years post-infusion for each participant, for up to two years from the entry date of the last participant
3

Progression free survival (PFS) and Overall survival (OS)

Evaluate PFS and OS in participants, in the phase II cohort (inclusive of those treated in the phase 1 arms at the RP2D)

Time frame
Up to two years after the last participant has entered.
4

Persistence and expansion

Evaluate persistence and expansion of CD19/CD22-CAR T cells in children and young adults with CD19+ and/or CD22+ B-ALL or lymphoma

Time frame
Up to two years after the last participant has entered.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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