Health TrialsbyHealthPanel

Co-administration of CART22-65s and huCART19 for B-ALL

ConditionsB-cell Acute Lymphoblastic LeukemiaB Lineage Lymphoblastic Lymphoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
AgeUp to 29
SponsorStephan Grupp MD PhD

About this trial

This study will evaluate the safety and efficacy of administering two CAR T cell products, huCART19 and CART22-65s, in children with advanced B cell Acute Lymphoblastic Leukemia (B-ALL).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Signed informed consent form

Cohort B: Patients with poor response to prior B cell directed engineered cell therapy

Patients with prior or current history of Central Nervous System 3 disease will be eligible if Central Nervous System disease is responsive to therapy

Documentation of CD19 and/or CD22 tumor expression in bone marrow, peripheral blood, Cerebrospinal fluid, or tumor tissue by flow cytometry at the time of last detectable disease. If the patient has experienced a relapse after CD19-directed and/or CD22-directed therapy, flow cytometry should be evaluated after this therapy to demonstrate CD19 and/or CD22 expression.

Disqualifiers

Active hepatitis B or active hepatitis C

HIV infection

Active acute or chronic Graft Vs. Host Disease requiring systemic therapy

Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s)

    Biological/Vaccine

    CART22-65s are autologous T cells that have been engineered to express an extracellular single chain antibody (scFv) with specificity for CD22 linked to an intracellular signaling molecule consisting of a tandem signaling domain comprised of the TCRζ signaling module linked to the 4-1BB costimulatory domain

  • Autologous, humanized anti-CD19 CAR T cell therapy (huCART19)

    Biological/Vaccine

    HuCART19 cells are autologous T cells that have been engineered to express an extracellular single chain antibody (scFv) with specificity for CD19 linked to an intracellular signaling molecule consisting of a tandem signaling domain comprised of the TCRζ signaling module linked to the 4-1BB costimulatory domain

Treatment groups

93 Participants
are divided into 2 treatment groups
Group A: Dose Finding ArmExperimental treatment 2 interventions
Group B: Expansion ArmExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Safety of CART22-65s and huCART19 co-administration

The safety of the administering CART22-65s and huCART19 will be measured by the monitoring the frequency and severity of adverse events in patients with advanced or refractory B-Cell Acute Lymphoblastic Leukemia or B Cell Lymphoblastic Lymphoma (B-LLy), including those previously treated with cell therapy.

Time frame
1 year
2

Efficacy of CART22-65s and huCART19 co-administration

The efficacy of CART22-65s and huCART19 co-administration will be measured by the evaluating the overall response rate in patients with advanced or refractory B cell hematologic malignancies, including those previously treated with cell therapy.

Time frame
1 year

Secondary outcomes

1

Manufacturing Feasibility

The manufacturing feasibility of manufacturing both CART22-65s and huCART19 will be measured by the percentage of manufactured products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility or due to tumor contamination.

Time frame
5 years
2

Anti-tumor response due to CART22-65s and huCART19 co-administration

Anti-tumor response due to CART22-65s and huCART19 co-administration will be measured by negative minimal residual disease (MRD) as measured by multiparameter flow cytometry at day 28.

Time frame
Day 28
3

Event Free Survival

1-year Event-Free Survival (EFS) in subjects with relapsed/refractory B-ALL (Cohort A) and in subjects with poor response to prior B cell directed engineered cell therapy (Cohort B)

Time frame
1 year
4

Relapse Free Survival

1-year relapse-free survival (RFS) rate in CAR-naïve subjects with relapsed/refractory B-ALL (Cohort A) and in CAR-exposed subjects with poor response to prior B cell directed engineered cell therapy (Cohort B)

Time frame
1 year

Other outcomes

Sponsors and contacts

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

Stephan Grupp MD PhD

Lead sponsor

Children's Hospital of Philadelphia

Sponsor institution

University of Pennsylvania

Collaborator

Source ClinicalTrials.gov
Apply now