Phase 2
Completed N=197
Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia
CD19-Positive Neoplastic Cells Present · leukemia · Diffuse Large B-Cell Lymphoma · Mantle Cell Lymphoma
Source: ClinicalTrials.gov NCT01865617 ↗
Enrolled (actual)
197
Serious AEs
95.9%
Results posted
May 2022
Primary outcomePrimary: Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy — 0; 0; 1; 0 Participants
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy |
0; 0; 1; 0; 1; 0 | — |
| PRIMARY Dose Limiting Toxicities |
3; 1; 1; 0; 2; 0 | — |
| PRIMARY Objective Response Rate of Complete Response and Partial Response |
32; 5; 1; 1; 18; 4 | — |
| PRIMARY Overall Survival |
12; 2; 1; 0; 13; 4 | — |
| PRIMARY Progression Free Survival |
2; 0; 0; 0; 1; 3 | — |
| SECONDARY Duration of Persistence of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T Cells |
33; 46; 23; 3; 14; 13 | — |
| SECONDARY Migration of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T Cells |
62; 24; 47; 49; 15; 37 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT01865617). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.