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

Plain-language summary

This Phase 1 study tests the safety of infusing the patient's own immune cells (19-28z CAR T cells) after high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT). The conditioning regimen includes carmustine, etoposide, cytarabine and melphalan, along with pegfilgrastim. Eligible participants are transplant-eligible patients aged 18 or older with aggressive B-cell non-Hodgkin lymphoma subtypes, including relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and transformed follicular lymphoma.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 1

Status

Active, not recruiting

Sponsor

Memorial Sloan Kettering Cancer Center

Intervention

Carmustine, Etoposide, Cytarabine, Melphalan, Pegfilgrastim, 19-28z T CELLS, Autologous Stem Cell Transplantation

Start date

4/1/2013

Estimated completion

4/1/2027

Countries

United States

Related genes

Locations

• Basking Ridge, United States
• Middletown, United States
• Montvale, United States
• Commack, United States
• Harrison, United States
• New York, United States
• Rockville Centre, United States

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

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.