Clinical trial · Interventional
Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia
Phase I/II Study of Immunotherapy for Advanced CD19+ Chronic Lymphocytic Leukemia, Acute Lymphoblastic Leukemia/Lymphoma and Non-Hodgkin Lymphoma With Defined Subsets of Autologous T Cells Engineered to Express a CD19-Specific Chimeric Antigen Receptor
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This phase I/II trial studies the side effects and best dose of laboratory treated T cells to see how well they work in treating patients with chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia that have come back or have not responded to treatment. T cells that are treated in the laboratory before being given back to the patient may make the body build an immune response to kill cancer cells.
Conditions
Conditions (13)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| CD19-Positive Neoplastic Cells Present | — | UNRESOLVED | — |
| Recurrent Adult Acute Lymphoblastic Leukemia | Adult Acute Lymphoblastic Leukemia | CURATED_BROADER | 0.78 |
| Recurrent Chronic Lymphocytic Leukemia | Chronic Lymphocytic Leukemia | CURATED_BROADER | 0.78 |
| Recurrent Diffuse Large B-Cell Lymphoma | Diffuse Large B-Cell Lymphoma | CURATED_BROADER | 0.80 |
| Recurrent Mantle Cell Lymphoma | Mantle Cell Lymphoma | CURATED_BROADER | 0.78 |
| Recurrent Non-Hodgkin Lymphoma | Non-Hodgkin Lymphoma | CURATED_BROADER | 0.78 |
| Recurrent Small Lymphocytic Lymphoma | Small Lymphocytic Lymphoma |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes | Biological | — | UNRESOLVED |
Design
Arms and outcomes
Arms (13)
- type
- EXPERIMENTAL
- label
- ALL (high tumor burden) dose level 1
- description
- Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: ALL Tumor Burden: high Dose level: 1 up to 2x105 EGFR+ cells/kg
- interventionNames
- Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
- type
- EXPERIMENTAL
- label
- ALL (high tumor burden) dose level 2
- description
- Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: ALL Tumor Burden: high Dose level: 2 up to 2x106 EGFR+ cells/kg
- interventionNames
- Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: INCLUSIONS FOR SCREENING AND LEUKAPHERESIS * Patients with CD19 expressing acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL) * Ability to understand and provide informed consent * Not human immunodeficiency virus (HIV) infected INCLUSIONS FOR CAR-T CELL THERAPY * Patients with: * CLL who are beyond first remission and who have failed combination chemoimmunotherapy with regimens containing a purine analogue and anti-CD20 antibody or who were not eligible for such therapy; patients with CLL for whom ibrutinib is now standard first line therapy, must have progressed on ibrutinib; patients with fludarabine refractory disease are eligible; patients may be treated following allogeneic hematopoietic cell transplant (HCT); for the concurrent ibrutinib cohort, patients must agree to continue on or be restarted on ibrutinib and must not have had prior intolerance to ibrutinib that would prevent this; patients managed with prior dose reductions for toxicity will continue at the reduced dose for the remainder of this study * Indolent NHL or mantle cell NHL who are beyond first remission and previously treated with chemoimmunotherapy or who were not eligible for such therapy; patients who have relapsed following autologous or allogeneic HCT are eligible * Aggressive NHL such as diffuse large B-cell lymphoma (DLBCL), who have relapsed or have residual disease following treatment with curative intent; patients should have relapsed following, or not be eligible for high-dose therapy and autologous HCT; patients with chemotherapy refractory disease or marrow involvement or comorbidities precluding successful autologous HCT are eligible; patients may be treated following allogeneic HCT * Patients with CD19 expressing, relapsed or refractory ALL * Patients with one of the above diagnoses whose disease state does not qualify but who have prognostic indicators that suggest a high risk of progression of disease may be screened and undergo leukapheresis; enrollment for T cell therapy would require meeting the full disease state eligibility * Confirmation of diagnosis * Evidence of CD19 expression by immunohistochemistry or flow cytometry on any prior or current tumor specimen or high likelihood of CD19 expression based on disease histology * Karnofsky performance status \>= 60% * All patients of childbearing potential must be willing to use a contraceptive method before, during, and for at least two months after the T cell infusion * Ability to understand and provide informed consent Exclusion Criteria: EXCLUSIONS FOR CAR-T CELL THERAPY * Patients requiring ongoing daily corticosteroid therapy at a dose of \> 15 mg of prednisone per day (or equivalent); pulsed corticosteroid use for disease control is acceptable * Active autoimmune disease requiring immunosuppressive therapy is excluded unless discussed with the Principal Investigator (PI) * Serum creatinine \> 2.5 mg/dL * Serum glutamic oxaloacetic transaminase (SGOT) \> 5 x upper limit of normal * Bilirubin \> 3.0 mg/dL * Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing; those with a forced expiratory volume in one second (FEV1) of \< 50 % of predicted will be excluded * Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected) \< 40% will be excluded * Significant cardiovascular abnormalities as defined by any one of the following: New York Heart Association (NYHA) class III or IV congestive heart failure, clinically significant hypotension, uncontrolled symptomatic coronary artery disease, or a documented ejection fraction of \< 35% * Uncontrolled active infection
References
Publications (12)
- DERIVEDOrtiz-Maldonado V, Liang EC, Huang JJ, Jeon Y, Hirayama AV, Kimble EL, Portuguese AJ, Khouderchah C, Braathen K, Torkelson A, Kirchmeier D, Shadman M, Maloney DG, Riddell SR, Turtle CJ, Gauthier J. A novel dose-dense strategy for CD19-directed CAR T-cell therapy is associated with durable responses without increased toxicity in patients with B-cell non-Hodgkin lymphoma. Haematologica. 2026 Jul 2. doi: 10.3324/haematol.2025.300321. Online ahead of print. PMID 42389828
- DERIVEDFiorenza S, Zheng Y, Purushe J, Bock TJ, Sarthy J, Janssens DH, Sheih AS, Kimble EL, Kirchmeier D, Phi TD, Gauthier J, Hirayama AV, Riddell SR, Wu Q, Gottardo R, Maloney DG, Yang JYH, Henikoff S, Turtle CJ. Histone marks identify novel transcription factors that parse CAR-T subset-of-origin, clinical potential and expansion. Nat Commun. 2024 Sep 27;15(1):8309. doi: 10.1038/s41467-024-52503-2. PMID 39333103
- DERIVEDLiang EC, Albittar A, Huang JJ, Hirayama AV, Kimble EL, Portuguese AJ, Chapuis A, Shadman M, Till BG, Cassaday RD, Milano F, Kiem HP, Riddell SR, Turtle CJ, Maloney DG, Gauthier J. Factors associated with long-term outcomes of CD19 CAR T-cell therapy for relapsed/refractory CLL. Blood Adv. 2023 Nov 28;7(22):6990-7005. doi: 10.1182/bloodadvances.2023011399. PMID 37774014
- DERIVEDJuluri KR, Wu QV, Voutsinas J, Hou J, Hirayama AV, Mullane E, Miles N, Maloney DG, Turtle CJ, Bar M, Gauthier J. Severe cytokine release syndrome is associated with hematologic toxicity following CD19 CAR T-cell therapy. Blood Adv. 2022 Apr 12;6(7):2055-2068. doi: 10.1182/bloodadvances.2020004142. PMID 34666344
- DERIVEDErnst 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
- DERIVEDGauthier J, Bezerra ED, Hirayama AV, Fiorenza S, Sheih A, Chou CK, Kimble EL, Pender BS, Hawkins RM, Vakil A, Phi TD, Steinmetz RN, Jamieson AW, Bar M, Cassaday RD, Chapuis AG, Cowan AJ, Green DJ, Kiem HP, Milano F, Shadman M, Till BG, Riddell SR, Maloney DG, Turtle CJ. Factors associated with outcomes after a second CD19-targeted CAR T-cell infusion for refractory B-cell malignancies. Blood. 2021 Jan 21;137(3):323-335. doi: 10.1182/blood.2020006770.