CD19-Specific T-cells in Treating Patients With Advanced Lymphoid Malignancies

NCT02529813 | Completed Phase 1 FDA Drug

• 4 other identifiers: 2013-1018NCI-2015-01492201521451159157
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I clinical trial studies the side effects and best dose of CD19-specific T-cells in treating patients with lymphoid malignancies that have spread to other places in the body and usually cannot be cured or controlled with treatment. Sometimes researchers change the deoxyribonucleic acid (DNA) (genetic material in cells) of donated T-cells (white blood cells that support the immune system) using a process called "gene transfer." Gene transfer involves drawing blood from the patient, and then separating out the T-cells using a machine. Researchers then perform a gene transfer to change the T-cells' DNA, and then inject the changed T-cells into the body of the patient. Injecting modified T-cells made from the patient may help attack cancer cells in patients with advanced B-cell lymphoma or leukemia.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of genetically modified, CD19-specified T cells

  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.

  Up to 30 days

Secondary Outcomes (2)

• The proportion of patients for which a T cell product could not be prepared

  Up to 1 year

• Proportion of patients experiencing response (complete response and partial response)

  Up to 1 year

Study Arms (1)

Arm I (CD19 positive chimeric antigen receptor T-cells)

EXPERIMENTAL

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; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Biological: Tisagenlecleucel

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Arm I (CD19 positive chimeric antigen receptor T-cells)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Arm I (CD19 positive chimeric antigen receptor T-cells)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (CD19 positive chimeric antigen receptor T-cells)

Tisagenlecleucel BIOLOGICAL

Given IV

Also known as: CART-19, CART19, CTL019, CTL019 T-cells, Kymriah, Tisagenlecleucel-T

Arm I (CD19 positive chimeric antigen receptor T-cells)

Eligibility Criteria

• Age: 1 Year - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Ziopharm Oncology: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasm, Residual; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Cyclophosphamide; fludarabine phosphate; tisagenlecleucel; CTL019 chimeric antigen receptor

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Leukemia, B-Cell; Chronic Disease; Disease Attributes

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Partow Kebriaei

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2015
• First Posted: August 20, 2015
• Study Start: December 16, 2015
• Primary Completion: November 8, 2021
• Study Completion: November 8, 2021
• Last Updated: June 30, 2022

Record last verified: 2022-06

Locations

US (1)