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

NCT01840566 | Active Not Recruiting Phase 1

• 1 other identifier: 12-117
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 7

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).

Conditions

Non-Hodgkin's Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• maximum tolerated dose (MTD)

  will be assessed utilizing a standard 3+3 cell dose escalation to determine the maximum tolerated dose of CD19+ CAR T cells

  2 years

• safety

  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

  2 years

Secondary Outcomes (2)

• 2 year progression-free (PFS)

  2 years

• overall survival (os)

  2 years

Study Arms (1)

HIGH DOSE CHEMOTHERAPY AND ASCT

EXPERIMENTAL

This is a phase 1 dose escalation study designed to determine the maximum tolerated dose (MTD) of CAR modified T cells in patients with relapsed and refractory aggressive B-NHL. Three dose levels (5 x 106 19-28z T cells/kg, 1 x 107 19-28z T cells/kg, and 2 x 107 19-28z T cells/kg) are considered for the MTD.

Drug: Carmustine; Drug: Etoposide; Drug: Cytarabine; Drug: Melphalan; Biological: Pegfilgrastim; Biological: 19-28z T CELLS; Procedure: Autologous Stem Cell Transplantation

Interventions

Carmustine DRUG

HIGH DOSE CHEMOTHERAPY AND ASCT

Etoposide DRUG

HIGH DOSE CHEMOTHERAPY AND ASCT

Cytarabine DRUG

HIGH DOSE CHEMOTHERAPY AND ASCT

Melphalan DRUG

HIGH DOSE CHEMOTHERAPY AND ASCT

Pegfilgrastim BIOLOGICAL

HIGH DOSE CHEMOTHERAPY AND ASCT

19-28z T CELLS BIOLOGICAL

HIGH DOSE CHEMOTHERAPY AND ASCT

Autologous Stem Cell Transplantation PROCEDURE

HIGH DOSE CHEMOTHERAPY AND ASCT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Karnofsky performance status ≤ 70 (see appendix VI).
• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited protocol activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (Limited protocol activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited protocol activites)

Rockville Centre, New York, 11553, United States

Location

Related Publications (2)

• 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.

  PMID: 34515338 DERIVED

• 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.

  PMID: 31262783 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Recurrence

Interventions

Carmustine; Etoposide; Cytarabine; Melphalan; pegfilgrastim

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Craig Sauter, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2013
• First Posted: April 25, 2013
• Study Start: April 1, 2013
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: December 3, 2025

Record last verified: 2025-12

Locations

US (7)