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
NCT ID: NCT03579927
Last Updated: 2020-01-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
WITHDRAWN
PHASE1/PHASE2
INTERVENTIONAL
2019-10-03
2019-10-03
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Umbilical & Cord Blood (CB) Derived CAR-Engineered NK Cells for B Lymphoid Malignancies
NCT03056339
CD19-Specific T Cells Post AlloSCT
NCT03579888
NK Cells in Cord Blood Transplantation
NCT01619761
Phase I Trial Integrating HLA-Haploidentical Anti-CD19 CAR-T Cells With Post-Transplantation Cyclophosphamide-Based HLA-Haploidentical Hematopoietic Cell Transplantation
NCT07162038
Phase II Study of CD5 CAR Engineered IL15-transduced Cord Blood-derived NK Cells in Conjunction With Lymphodepleting Chemotherapy for the Management of Aggressive T Cell Hematological Malignancies
NCT07137481
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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.
Autologous Hematopoietic Stem Cell Transplantation
Undergo ASCT
Carmustine
Given IV
Cytarabine
Given IV
Etoposide
Given IV
Filgrastim
Given SC
Melphalan
Given IV
Rituximab
Given IV
Umbilical Cord Blood-derived Natural Killer Cells
Given CAR.CD19-CD28-zeta-2A-iCasp9-IL15-transduced CB-NK cells IV
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Autologous Hematopoietic Stem Cell Transplantation
Undergo ASCT
Carmustine
Given IV
Cytarabine
Given IV
Etoposide
Given IV
Filgrastim
Given SC
Melphalan
Given IV
Rituximab
Given IV
Umbilical Cord Blood-derived Natural Killer Cells
Given CAR.CD19-CD28-zeta-2A-iCasp9-IL15-transduced CB-NK cells IV
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Patients with B-cell lymphoma who are candidates to autologous stem-cell transplantation, including: 1. Primary refractory or relapsed diffuse large B-cell lymphoma in response to salvage treatment. 2. Primary refractory or relapsed follicular lymphoma or other indolent B-cell histology in response to salvage treatment. 3. Chemosensitive mantle-cell lymphoma in first or later line of treatment. 4. Patients with B cell lymphoma (all CD19+ NHL) with progressive or refractory disease who would otherwise not be candidates for autologous stem cell transplantation.
3. Adequate organ function: Renal: Creatinine clearance (as estimated by Cockcroft Gault) \>/= 60 cc/min. Hepatic: ALT/AST \</= 2.5 x ULN or \</= 5 x ULN if documented liver metastases, Total bilirubin \</= 1.5 mg/dL, except in subjects with Gilbert's Syndrome in whom total bilirubin must be \</= 3.0 mg/dL. Cardiac: Cardiac ejection fraction \>/= 50%, no evidence of pericardial effusion as determined by an ECHO, and no clinically significant ECG findings. Pulmonary: No clinically significant pleural effusion, Baseline oxygen saturation \> 92% on room air.
4. Patients must have a cord blood unit available which is matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens.
5. Availability of autologous peripheral blood stem cell graft, containing at least 6.0 x 10\^6 CD34+ cells/kg.
6. Performance status \< 2 (ECOG).
7. Negative Beta HCG in woman with child-bearing potential.
8. All participants who are able to have children must practice effective birth control while on study. Acceptable forms of birth control for female patients include: hormonal birth control, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence, for the length of the study. If the participant is a female and becomes pregnant or suspects pregnancy, she must immediately notify her doctor. If the participant becomes pregnant during this study, she will be taken off this study. Men who are able to have children must use effective birth control while on the study. If the male participant fathers a child or suspects that he has fathered a child while on the study, he must immediately notify his doctor.
9. Signed consent to long-term follow-up protocol PA17-0483.
Exclusion Criteria
2. Grade \>/= 3 non-hematologic toxicity from prior therapy that has not resolved to \</= G1.
3. Prior whole brain irradiation.
4. Active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA \>/= 10,000 copies/mL, or \>/= 2,000 IU/mL).
5. Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology.
6. Active infection requiring parenteral antibiotics.
7. HIV infection.
8. Radiation therapy in the month prior to enroll.
9. Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials for management. Note: Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
10. Concomitant use of other investigational agents.
18 Years
70 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
M.D. Anderson Cancer Center
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Katy Rezvani
Role: PRINCIPAL_INVESTIGATOR
M.D. Anderson Cancer Center
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
M D Anderson Cancer Center
Houston, Texas, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
Related Links
Access external resources that provide additional context or updates about the study.
MD Anderson Cancer Center Website
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2018-01111
Identifier Type: REGISTRY
Identifier Source: secondary_id
2017-0295
Identifier Type: OTHER
Identifier Source: secondary_id
2017-0295
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.