High Dose Therapy and Autologous Stem Cell Transplantation Followed by Infusion of Chimeric Antigen Receptor (CAR) Modified T-Cells Directed Against CD19+ B-Cells for Relapsed and Refractory Aggressive B Cell Non-Hodgkin Lymphoma

Conditions

Non-Hodgkin's Lymphoma

Keywords

Relapsed, Refractory, Autologous Stem Cell Transplantation, HIGH DOSE CHEMOTHERAPY, 19-28z T cells/kg, 12-117

Brief summary

The purpose of this study is to test the safety of delivering the patients' own immune cells, called T cells, after the high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT).

Tariq Iqtidar Sadiq Syed, Syed Maaz Abdullah, Tayyab Rehan, Muhaddis Ejaz Ahmad, Syeda Sabeeka Batool et al. (14 authors)

Blood2019-11-137 citations

10.1182/blood-2019-127452

CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma

Craig S. Sauter, Brigitte Sénéchal, Isabelle Rivière, Ai Ni, Yvette Bernal et al. (21 authors)

Blood2019-07-0290 citations

10.1182/blood.2018883421

A PHASE I TRIAL OF 19‐28Z CAR‐T CELLS POST‐HIGH DOSE THERAPY AND AUTOLOGOUS TRANSPLANTATION (HDT‐ASCT) FOR RELAPSED AND REFRACTORY (R/R) B‐CELL NON‐HODGKIN LYMPHOMA (B‐NHL)

Craig S. Sauter, Isabelle Rivière, Brigitte Sénéchal, Ai Ni, Yvette Bernal et al. (15 authors)

Hematological Oncology2017-06-012 citations

10.1002/hon.2437_128

Phase I trial of 19-28z chimeric antigen receptor modified T cells (19-28z CAR-T) post-high dose therapy and autologous stem cell transplant (HDT-ASCT) for relapsed and refractory (rel/ref) aggressive B-cell non-Hodgkin lymphoma (B-NHL).

Craig S. Sauter, Isabelle Rivière, Yvette Bernal, Xiuyan Wang, Terence J. Purdon et al. (13 authors)

Journal of Clinical Oncology2015-05-2036 citations

10.1200/jco.2015.33.15_suppl.8515

Interventions

DRUGCarmustine

DRUGEtoposide

DRUGCytarabine

DRUGMelphalan

BIOLOGICALPegfilgrastim

BIOLOGICAL19-28z T CELLS

PROCEDUREAutologous Stem Cell Transplantation

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

Transplant eligible patients will be eligible if criteria met per below. Inclusion Criteria: * Patients ≥ 18 years of age with aggressive B-cell non-Hodgkin lymphoma subtypes including, relapsed or refractory diffused large B-cell lymphoma (DLBCL), and transformed follicular lymphoma meeting at least one of the following criteria: * Bone marrow involvement at the time of relapse or refractory disease and not appropriate for allogeneic transplantation. * PET positive disease outside of one radiation port unless single-port disease treated with prior radiotherapy within the port, following \> or = to 2 cycles of salvage chemotherapy, still achieving chemosensitive status 1999 IWG criteria (section 12.2 and 12.383). * Creatinine ≤ 1.5 mg/100 ml (or measured 24 hour creatinine clearance of ≥ 50 cc/min) * Bilirubin \<2.0 mg/100 ml, AST and ALT \<3x the upper-limit of normal, PT and PTT \< 2x normal outside the setting of stable chronic anticoagulation therapy, * Adequate cardiac function (LVEF\>40%) as assessed by ECHO or MUGA scan performed within 1 month of treatment. * Adequate pulmonary function as assessed by DLCO of \> or = to 45% adjusted for hemoglobin. * Life expectancy of \> 3 months.

Exclusion criteria

* Karnofsky performance status ≤ 70 (see appendix VI). * Patients with other aggressive B-cell malignancies including, but not limited to: Burkitt lymphoma, transformed CLL/SLL and transformed marginal zone lymphoma that are not included in 6.1 inclusion criteria. * Patients previously treated with autologous or allogeneic bone marrow or stem cell transplantation are ineligible. * Other past or current malignancy unless in the opinion of the investigator it does not contraindicate participation in the study. * Uncontrolled bacterial, viral or fungal infection. * Patients with HIV, active hepatitis B or hepatitis C infection.

Design outcomes

Primary

Measure	Time frame	Description
maximum tolerated dose (MTD)	2 years	will be assessed utilizing a standard 3+3 cell dose escalation to determine the maximum tolerated dose of CD19+ CAR T cells
safety	2 years	Toxicity will be graded on a scale of 1 to 5 as described by the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0

Secondary

Measure	Time frame
2 year progression-free (PFS)	2 years
overall survival (os)	2 years

Countries

United States

Contacts

PRINCIPAL_INVESTIGATORCraig Sauter, MD

Memorial Sloan Kettering Cancer Center

Outcome results

None listed