CD19-Specific T-cells in Treating Patients With Advanced Lymphoid Malignancies
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| ClinicalTrials.gov Identifier: NCT02529813 |
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Recruitment Status :
Completed
First Posted : August 20, 2015
Last Update Posted : November 16, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Biphenotypic Leukemia Acute Lymphoblastic Leukemia Blasts 5 Percent or More of Bone Marrow Nucleated Cells CD19 Positive Minimal Residual Disease Non-Hodgkin Lymphoma Small Lymphocytic Lymphoma Stage III Chronic Lymphocytic Leukemia Stage IV Chronic Lymphocytic Leukemia | Drug: Cyclophosphamide Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Biological: Tisagenlecleucel | Phase 1 |
PRIMARY OBJECTIVES:
I. To determine the safety and maximum tolerated dose of genetically modified, CD19-specific T cells administered into patients with CD19+ advanced lymphoid malignancies.
SECONDARY OBJECTIVES:
I. To screen for the development of host immune responses against the CD19-specific chimeric antigen receptor (CAR).
II. To describe the homing ability of the infused T cells. III. To assess disease response. IV. To determine persistence of CAR+ T cells.
OUTLINE: This is a dose escalation study of CD19 positive chimeric antigen receptor T-cells.
LYMPHODEPLETING CHEMOTHERAPY: Patients may receive standard chemotherapy comprised of fludarabine phosphate intravenously (IV) over 1 hour and cyclophosphamide IV over 3 hours on days -5 to -3 or cyclophosphamide IV every 12 hours on days -5 to -3 at the discretion of the treating physician.
Within 30 days post completion of lymphodepletion, patients receive CD19 positive chimeric antigen receptor T-cells IV over 15-30 minutes on day 0, or split into two portions on days 0 and 1.
After completion of study treatment, patients are followed up for at least 15 years.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 26 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | CD19+ Chimeric Antigen Receptor T Cells for Patients With Advanced Lymphoid Malignancies |
| Actual Study Start Date : | December 16, 2015 |
| Actual Primary Completion Date : | November 8, 2021 |
| Actual Study Completion Date : | November 8, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I (CD19 positive chimeric antigen receptor T-cells)
LYMPHODEPLETING CHEMOTHERAPY: Patients may receive standard chemotherapy comprised of fludarabine phosphate IV over 1 hour and cyclophosphamide IV over 3 hours on days -5 to -3 or cyclophosphamide IV every 12 hours on days -5 to -3 at the discretion of the treating physician. Within 30 days post completion of lymphodepletion, patients receive CD19 positive chimeric antigen receptor T-cells IV over 15-30 minutes on day 0, or split into two portions on days 0 and 1. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Fludarabine Phosphate Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Biological: Tisagenlecleucel Given IV
Other Names:
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- Maximum tolerated dose of genetically modified, CD19-specified T cells [ Time Frame: Up to 30 days ]Will be defined as the highest dose for which the posterior probability of toxicity is closest to 25%. Demographic and clinical characteristics will be summarized using descriptive statistics by dose level. The number of patients with dose limiting toxicities will be reported at each dose level.
- The proportion of patients for which a T cell product could not be prepared [ Time Frame: Up to 1 year ]Computed with a corresponding 95% confidence interval.
- Proportion of patients experiencing response (complete response and partial response) [ Time Frame: Up to 1 year ]Estimated with a corresponding 95% confidence interval.
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| Ages Eligible for Study: | 1 Year to 80 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients with a history of CD19+ lymphoid malignancy defined as acute lymphoblastic leukemia, acute biphenotypic leukemia, non-Hodgkin's lymphoma, small lymphocytic lymphoma, or chronic lymphocytic leukemia with active disease defined by presence of > 5% malignant blasts in bone marrow and/or peripheral blood, and/or minimal residual disease by flow cytometry or molecular analysis for fusion proteins, and/or positive imaging for extramedullary disease; patients must have measurable disease at time of study treatment
- Confirmed history of CD19 positivity by flow cytometry for malignant cells
- Lansky/Karnofsky performance scale > 60%
- Patient able to provide written informed consent; parent or guardian of minor patient able to provide written informed consent
- Patient able to provide written informed consent for the long-term follow-up gene therapy study: 2006-0676; parent or guardian of minor patient able to provide written informed consent for the long-term follow-up gene therapy study: 2006-0676
Exclusion Criteria:
- Positive beta human chorionic gonadotropin (HCG) in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females
- Patients with known allergy to bovine or murine products
- Positive serology for human immunodeficiency virus (HIV)
- Active hepatitis B or active hepatitis C
- Has received donor lymphocyte infusion (DLI) product within 6 weeks of CAR T cell infusion
- Has received allogeneic hematopoietic stem cell transplant within 3 months of CAR T cell infusion; hematopoietic stem cell transplant (HSCT) > 3 months from CAR T cell infusion eligible
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02529813
| United States, Texas | |
| M D Anderson Cancer Center | |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: | Partow Kebriaei | M.D. Anderson Cancer Center |
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT02529813 |
| Other Study ID Numbers: |
2013-1018 NCI-2015-01492 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 20152145 1159157 2013-1018 ( Other Identifier: M D Anderson Cancer Center ) |
| First Posted: | August 20, 2015 Key Record Dates |
| Last Update Posted: | November 16, 2021 |
| Last Verified: | November 2021 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Lymphoma Leukemia Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphocytic, Chronic, B-Cell Neoplasm, Residual Leukemia, Biphenotypic, Acute Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Leukemia, B-Cell Neoplastic Processes |
Pathologic Processes Cyclophosphamide Fludarabine Fludarabine phosphate Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antimetabolites, Antineoplastic Antimetabolites |