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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carmustine | Drug |
| ||
| Etoposide |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 2 year progression-free (PFS) | 2 years | |
| overall survival (os) | 2 years |
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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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Craig Sauter, MD | Memorial Sloan Kettering Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities) | Basking Ridge | New Jersey | 07920 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34515338 | Derived | 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. | |
| 31262783 |
| Label | URL |
|---|---|
| Memorial Sloan Kettering Cancer Center | View source |
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|
| Cytarabine | Drug |
|
| Melphalan | Drug |
|
| Pegfilgrastim | Biological |
|
| 19-28z T CELLS | Biological |
|
| Autologous Stem Cell Transplantation | Procedure |
|
| Memorial Sloan Kettering Monmouth (Limited protocol activities) |
| Middletown |
| New Jersey |
| 07748 |
| United States |
| Memorial Sloan Kettering Bergen (Limited Protocol Activities) | Montvale | New Jersey | 07645 | United States |
| Memorial Sloan Kettering Commack (Limited protocol activities) | Commack | New York | 11725 | United States |
| Memorial Sloan Kettering Westchester (Limited Protocol Activities) | Harrison | New York | 10604 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Memorial Sloan Kettering Nassau (Limited protocol activites) | Rockville Centre | New York | 11553 | United States |
| 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. |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D002330 | Carmustine |
| D005047 | Etoposide |
| D003561 | Cytarabine |
| D008558 | Melphalan |
| C455861 | pegfilgrastim |
| ID | Term |
|---|---|
| D009607 | Nitrosourea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D009603 | Nitroso Compounds |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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