NCT03103971

huJCAR014 CAR-T Cells in Treating Adult Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia

A Two-Stage Phase 1 Open-Label Study of huJCAR014, CD19-Targeted Chimeric Antigen Receptor (CAR)-Modified T Cells Bearing a Human Binding Domain, in Adult Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma and Acute Lymphocytic Leukemia

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 55 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects of huJCAR014 in treating patients with relapsed or refractory B-cell non-Hodgkin lymphoma or acute lymphoblastic leukemia. huJCAR014 CAR-T cells are made in the laboratory by genetically modifying a patient's T cells and may specifically kill cancer cells that have a molecule CD19 on their surfaces. In Stage 1, dose-finding studies will be conducted in 3 cohorts: 1. Aggressive B cell NHL 2. Low burden ALL 3. High burden ALL In Stage 2, studies may be conducted in one or more cohorts to collect further safety, PK, and efficacy information at the huJCAR014 dose level(s) selected in Stage 1 for the applicable cohort(s). There are two separate cohorts for stage 2: 1. Cohort 2A, CAR-naïve (n=10): patients who have never received CD19 CAR-T cell therapy. 2. Cohort 2B, CAR-exposed (n=27): patients who have previously failed CD19 CAR-T cell therapy.

Detailed description

OUTLINE: This is a dose-escalation study of huJCAR014. Patients undergo leukapheresis. Beginning 1-2 weeks after leukapheresis, patients undergo lymphodepleting chemotherapy comprising either cyclophosphamide intravenously (IV) daily for 1 day and fludarabine IV daily for 3 days or cyclophosphamide and fludarabine IV daily for 3 days. Alternative lymphodepleting chemotherapy regimens maybe used if patient's clinical situation or other logistical factors dictate otherwise. Within 36-96 hours after completion of lymphodepleting chemotherapy, patients receive huJCAR014 IV over 20-30 minutes on day 0. After completion of study treatment, patients are followed up every 30 days for the first 3 months, every 3 months for up to 12 months, and then yearly for 15 years.

Conditions

• Recurrent Adult Acute Lymphoblastic Leukemia
• Recurrent B-Cell Non-Hodgkin Lymphoma
• Recurrent Diffuse Large B-Cell Lymphoma
• Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma
• Refractory Adult Acute Lymphoblastic Leukemia
• Refractory B-Cell Non-Hodgkin Lymphoma
• Refractory Diffuse Large B-Cell Lymphoma
• Refractory Primary Mediastinal (Thymic) Large B-Cell Lymphoma
• Recurrent Transformed Non-Hodgkin Lymphoma
• Recurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements
• Refractory High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements
• Recurrent B Acute Lymphoblastic Leukemia
• Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
• Refractory B Acute Lymphoblastic Leukemia
• Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements

Interventions

Type	Name	Description
BIOLOGICAL	Autologous Human Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes	Given IV
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
PROCEDURE	Leukapheresis	Undergo leukapheresis
OTHER	Pharmacological Study	Correlative studies

Timeline

• Start date: 2017-11-03
• Primary completion: 2023-03-23
• Completion: 2024-03-23
• First posted: 2017-04-07
• Last updated: 2024-04-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study