Umbilical & Cord Blood (CB) Derived CAR-Engineered NK Cells for B Lymphoid Malignancies
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|ClinicalTrials.gov Identifier: NCT03056339|
Recruitment Status : Recruiting
First Posted : February 17, 2017
Last Update Posted : July 19, 2021
If you are reading and signing this form on behalf of a potential participant, please note: Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant.
The goal of this clinical research study is to learn if giving genetically changed immune cells, called CAR-NK cells, after chemotherapy will improve the disease in stem cell transplant patients with relapsed (has returned) and/or refractory (has not responded to treatment) B-cell lymphoma or leukemia. Also, researchers want to find the highest tolerable dose of CAR-NK cells to give to patients with relapsed or refractory B-cell lymphoma or leukemia. The safety of this treatment will also be studied.
This is an investigational study. The making of and infusion of genetically changed NK cells and the drug AP1903 (if you receive it, explained below) are not FDA approved or commercially available for use in this type of disease. They are currently being used for research purposes only. The chemotherapy drugs in this study (fludarabine, cyclophosphamide, and mesna) are commercially available and FDA approved.
Up to 36 patients will take part in this study. All will be enrolled at MD Anderson.
|Condition or disease||Intervention/treatment||Phase|
|B-Lymphoid Malignancies Acute Lymphocytic Leukemia Chronic Lymphocytic Leukemia Non-hodgkin Lymphoma||Drug: Fludarabine Drug: Cyclophosphamide Drug: Mesna Biological: iC9/CAR.19/IL15-Transduced CB-NK Cells Drug: AP1903||Phase 1 Phase 2|
To determine the safety and relative efficacy of Chimeric antigen receptors (CAR).CD19-CD28-zeta-2A-iCasp9-IL15-transduced cord blood natural killer (CB-NK) cells in patients with relapsed/refractory CD19+ B lymphoid malignancies.
- To assess the overall response rate (complete and partial response rates).
- To quantify persistence of infused allogeneic donor CAR-transduced CB-derived NK cells in the recipient.
- To conduct comprehensive immune reconstitution studies.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Dose Escalation Study Phase I/II of Umbilical Cord Blood-Derived CAR-Engineered NK Cells in Conjunction With Lymphodepleting Chemotherapy in Patients With Relapsed/Refractory B-Lymphoid Malignancies|
|Actual Study Start Date :||June 21, 2017|
|Estimated Primary Completion Date :||June 2022|
|Estimated Study Completion Date :||June 2022|
Experimental: Fludarabine + Cyclophosphamide + CAR-NK Cells
On Days -5, -4, and -3, participants receive Fludarabine and Cyclophosphamide. Participants also receive Mesna before and after the cyclophosphamide dose.
On Day 0, participants receive genetically modified NK cells as a cell infusion.
If participant has graft-versus-host disease (GvHD) or cytokine release syndrome after the NK cell infusion, they receive AP1903 by vein and possibly steroids by mouth or by vein.
30 mg/m2 by vein on Days -5 to -3.
300 mg/m2 by vein on Days -5 to -3.
300 mg/m2 by vein on Days -5 to -3 before and after the cyclophosphamide dose.
Other Name: Mesnex
Biological: iC9/CAR.19/IL15-Transduced CB-NK Cells
Infusion of iC9/CAR.19/IL15-transduced CB-NK cells on Day 0 by vein.
Starting dose: 10E5
Other Name: NK cells
If participant has graft-versus-host disease (GvHD) or cytokine release syndrome after the NK cell infusion, they will receive AP1903 0.4 mg/kg administered as an intravenous infusion.
- Optimal NK Cell Dose Level of Chimeric Antigen Receptors (CAR).CD19-CD28-zeta-2A-iCasp9-IL15-Transduced Cord Blood Natural Killer (CB-NK) Cells in Patients with Relapsed/Refractory CD19+ B Lymphoid Malignancies [ Time Frame: 45 days ]Dose-finding done using the sequentially adaptive phase I-II EffTox trade-off-based design. Toxicity is defined as a grade 3 or 4 GVHD within 45 days of NK cell infusion.
- Toxicity of Chimeric Antigen Receptors (CAR).CD19-CD28-zeta-2A-iCasp9-IL15-Transduced Cord Blood Natural Liller (CB-NK) Cells in Patients with Relapsed/Refractory CD19+ B Lymphoid Malignancies [ Time Frame: 2 weeks after NK cell infusion ]Toxicity defined as cytokine release storm (CRS) within 2 weeks of NK cell infusion requiring transfer to intensive care.
- Efficacy of Chimeric Antigen Receptors (CAR).CD19-CD28-zeta-2A-iCasp9-IL15-Transduced Cord Blood Natural Killer (CB-NK) Cells in Patients with Relapsed/Refractory CD19+ B Lymphoid Malignancies [ Time Frame: 30 days after NK cell infusion ]Efficacy defined as the patient being alive and in remission at day 30 post NK cell infusion.
- Response of Chimeric Antigen Receptors (CAR).CD19-CD28-zeta-2A-iCasp9-IL15-Transduced Cord Blood Natural Killer (CB-NK) Cells in Patients with Relapsed/Refractory CD19+ B Lymphoid Malignancies [ Time Frame: 100 days after NK cell infusion ]Unadjusted distributions of the time-to-event outcomes estimated using the method of Kaplan and Meier and their relationship to prognostic covariates and NK cell dose level evaluated by Bayesian piecewise exponential survival regression.
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): NCT03056339
|Contact: Loretta Nastoupil, MD||(713) firstname.lastname@example.org|
|Contact: Bethany Overman, RN,BSN,CPN||713-745-4567|
|United States, Texas|
|University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Clinical Research Operations email@example.com|
|Principal Investigator:||Loretta Nastoupil, MD||M.D. Anderson Cancer Center|