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
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03579927|
Recruitment Status : Not yet recruiting
First Posted : July 9, 2018
Last Update Posted : August 6, 2018
|Condition or disease||Intervention/treatment||Phase|
|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||Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Carmustine Drug: Cytarabine Drug: Etoposide Biological: Filgrastim Drug: Melphalan Biological: Rituximab Biological: Umbilical Cord Blood-derived Natural Killer Cells||Phase 1 Phase 2|
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Estimated Study Start Date :||September 21, 2018|
|Estimated Primary Completion Date :||March 21, 2019|
|Estimated Study Completion Date :||March 21, 2019|
Experimental: Treatment (CAR transduced CB-NK cells, chemotherapy, ASCT)
Participants receive rituximab IV over 3 hours on days -14 and -8, carmustine IV over 2 hours on day -13, etoposide IV over 3 hours 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 ASCT on day 0. Beginning day 0, participants receive filgrastim SC QD until evidence of an ANC of 0.5 x 10^9/L per 3 consecutive days.
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Biological: Umbilical Cord Blood-derived Natural Killer Cells
Given CAR.CD19-CD28-zeta-2A-iCasp9-IL15-transduced CB-NK cells IV
- Incidence of adverse events defined as graft failure, grade 3, 4 graft versus host disease, grade 3,4 cytokine release syndrome, grade 3, 4, neuro-toxicity, or death from any cause [ Time Frame: Up to 30 days within natural killer (NK) cell infusion ]Frequencies of toxicity will be summarized by dose. The relationships between toxicity and efficacy as functions of dose and other covariates will be assessed by fitting Bayesian regression models.
- Complete response (CR) or partial response (PR) [ Time Frame: At day 30 post NK cell infusion ]Efficacy is defined as the patient being alive and in CR or PR at day 30 post NK cell infusion. Frequencies of efficacy will be summarized by dose. The relationships between toxicity and efficacy as functions of dose and other covariates will be assessed by fitting Bayesian regression models.
- Progression-free survival (PFS) time [ Time Frame: At day 100 ]Unadjusted distributions of the time-to-event outcome PFS will be estimated using the method of Kaplan and Meier. The relationship of PFS to prognostic covariates and NK cell dose level will be evaluated by Bayesian piecewise exponential survival regression.
- Overall survival (OS) time [ Time Frame: At day 100 ]Unadjusted distributions of the time-to-event outcome OS will be estimated using the method of Kaplan and Meier. The relationship of OS to prognostic covariates and NK cell dose level will be evaluated by Bayesian piecewise exponential survival regression.
- Response status [ Time Frame: 16 weeks ]Participants have a bone marrow aspiration and/or biopsy to check the status of the disease.
- Number of chimeric antigen receptor (CAR) NK cells in blood by flow cytometry [ Time Frame: Up to 16 weeks post CAR NK cell infusion ]The number of CAR NK cells in blood by flow cytometry will be measured on days 3, 7, 14, 21, and at 4 weeks, 8 weeks, 12 weeks, and 16 weeks post CAR NK cell infusion. In addition to preliminary graphical analysis to assess possible patterns over time Bayesian longitudinal regression using a generalized Poisson regression model for the count at each time point as a function of patient baseline covariates, and random latent patient effects to induce within-patient correlation among each patient's vector of CAR NK cell counts.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03579927
|Contact: Katy Rezvanifirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Not yet recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Katy Rezvani||M.D. Anderson Cancer Center|