Recurrent Mantle Cell Lymphoma Clinical Trial
Official title:
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
Verified date | May 2022 |
Source | Fred Hutchinson Cancer Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 204 |
Est. completion date | March 26, 2021 |
Est. primary completion date | March 26, 2021 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
United States | Fred Hutch/University of Washington Cancer Consortium | Seattle | Washington |
Lead Sponsor | Collaborator |
---|---|
Fred Hutchinson Cancer Center | National Cancer Institute (NCI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
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 | Death within 8 weeks of the study cell infusion thought to be definitely or probably related to CAR T cell therapy will be assessed. | Within 8 weeks of the study cell infusion | |
Primary | Dose Limiting Toxicities | Outcome will be reported as a count of participants that experienced a dose limiting toxicity on the study within 30 days post infusion. | 30 days | |
Primary | Objective Response Rate of Complete Response and Partial Response | Outcome will be reported as the count of patients per arm that experienced a complete response/partial response.
Complete response (CR): CR per Lugano criteria for nodal disease and minimal residual disease (MRD)-negative CR by flow cytometry for marrow disease. Partial response (PR): > 50% reduction of the sum of the products of the perpendicular diameters of marker lesions, no progression of any existing lesions, and no new lesions. |
Up to 1 year | |
Primary | Overall Survival | Outcome will be reported as a count of patients who survived up to 1 year post infusion. | Up to 1 year | |
Primary | Progression Free Survival | Outcome will be reported as the count of patients per arm that survived and whose disease did not progress in the 1 year timeframe post infusion. | Up to 1 year | |
Secondary | Duration of Persistence of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T Cells | Duration of persistence of adoptively transferred CD19 chimeric antigen receptor (CAR)-T cells. Outcome will be reported for each of the 3 cohorts on the study. Outcome data is both count of patients alive after 1 year and count of patients with CAR-T cells detected at 1 year. | Up to day 365 | |
Secondary | Migration of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T Cells | Migration of adoptively transferred CD19 chimeric antigen receptor (CAR)-T cells. Outcome will be reported for each of the 3 cohorts on the study. Outcome data is both count of patients with bone marrow disease involvement and count of patients with CAR-T cells detected in bone marrow at restaging. | Up to 1 year |
Status | Clinical Trial | Phase | |
---|---|---|---|
Withdrawn |
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