Clinical trial NCT01840566: 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
Official title: A Phase I Trial of 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Non-Hodgkin's Lymphoma
Keywords: Relapsed
Refractory
Autologous Stem Cell Transplantation
HIGH DOSE CHEMOTHERAPY
19-28z T cells/kg
12-117
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2013-04-25
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility 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.

Primary outcomes:
measure: maximum tolerated dose (MTD)
timeFrame: 2 years
measure: safety
timeFrame: 2 years
Secondary outcomes:
measure: 2 year progression-free (PFS)
timeFrame: 2 years
measure: overall survival (os)
timeFrame: 2 years
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (Limited protocol activities)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (Limited Protocol Activities)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack (Limited protocol activities)
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (Limited Protocol Activities)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering Nassau (Limited protocol activites)
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Mark Geyer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Sauter CS, Senechal B, Riviere I, Ni A, Bernal Y, Wang X, Purdon T, Hall M, Singh AN, Szenes VZ, Yoo S, Dogan A, Wang Y, Moskowitz CH, Giralt S, Matasar MJ, Perales MA, Curran KJ, Park J, Sadelain M, Brentjens RJ. CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma. Blood. 2019 Aug 15;134(7):626-635. doi: 10.1182/blood.2018883421. Epub 2019 Jul 1.