NCT03579927

CAR.CD19-CD28-zeta-2A-iCasp9-IL15-Transduced Cord Blood NK Cells, High-Dose Chemotherapy, and Stem Cell Transplant in Treating Participants With B-cell Lymphoma

Immunotherapy With Ex Vivo-Expanded Cord Blood-Derived CAR-NK Cells Combined With High-Dose Chemotherapy and Autologous Stem Cell Transplantation for B-Cell Lymphoma

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of chimeric antigen receptor (CAR).CD19-CD28-zeta-2A-iCasp9-IL15-transduced cord blood NK cells when given together with high-dose chemotherapy and stem cell transplant and to see how well they work in treating participants with B-cell lymphoma. Cord blood-derived CAR-NK cells may react against the B-cell lymphoma cells in the body, which may help to control the disease. Giving chemotherapy before a stem cell transplant may help kill any cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

Detailed description

PRIMARY OBJECTIVES: I. To establish the safety and relative efficacy of CAR.CD19-CD28-zeta-2A-iCasp9-IL15-transduced cord blood natural killer (CB-NK) cells in patients with B cell non-Hodgkin lymphoma (NHL) undergoing high dose chemotherapy and autologous stem cell transplantation. SECONDARY OBJECTIVES: I. To estimate the relapse-free survival (RFS). II. To estimate the overall survival (OS). III. To quantify the persistence of infused CAR.CD19-CD28-zeta-2A-iCasp9-IL15-transduced CB-NK cells in the recipient. OUTLINE: This is a phase I, dose-escalation study of CAR.CD19-CD28-zeta-2A-iCasp9-IL15-transduced CB-NK cells followed by a phase II study. Participants receive rituximab intravenously (IV) over 3 hours on days -14 and -8, carmustine IV over 2 hours on day -13, etoposide IV over 3 hours twice daily (BID) on days -12 to -9, cytarabine IV over 1 hour BID on days -12 to -9, melphalan IV over 30 minutes on day -8, CAR.CD19-CD28-zeta-2A-iCasp9-IL15-transduced CB-NK cells IV over 1 hour on day -5. Participants undergo autologous stem cell transplantation (ASCT) on day 0. Beginning day 0, participants receive filgrastim subcutaneously (SC) once daily (QD) until evidence of an absolute neutrophil count (ANC) of 0.5 x 10\^9/L per 3 consecutive days. After completion of study treatment, participants are followed for up to 15 years.

Conditions

• CD19 Positive
• Mantle Cell Lymphoma
• Recurrent Diffuse Large B-Cell Lymphoma
• Recurrent Follicular Lymphoma
• Refractory B-Cell Non-Hodgkin Lymphoma
• Refractory Diffuse Large B-Cell Lymphoma
• Refractory Follicular Lymphoma

Interventions

Type	Name	Description
PROCEDURE	Autologous Hematopoietic Stem Cell Transplantation	Undergo ASCT
DRUG	Carmustine	Given IV
DRUG	Cytarabine	Given IV
DRUG	Etoposide	Given IV
BIOLOGICAL	Filgrastim	Given SC
DRUG	Melphalan	Given IV
BIOLOGICAL	Rituximab	Given IV
BIOLOGICAL	Umbilical Cord Blood-derived Natural Killer Cells	Given CAR.CD19-CD28-zeta-2A-iCasp9-IL15-transduced CB-NK cells IV

Timeline

• Start date: 2019-10-03
• Primary completion: 2019-10-03
• Completion: 2019-10-03
• First posted: 2018-07-09
• Last updated: 2020-01-29

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study