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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02529813
Recruitment Status : Completed
First Posted : August 20, 2015
Last Update Posted : November 16, 2021
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Ziopharm Oncology
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

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

Detailed Description:

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.

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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
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:
  • (-)-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

Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • SH T 586

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Tisagenlecleucel
Given IV
Other Names:
  • CART-19
  • CART19
  • CTL019
  • CTL019 T-cells
  • Kymriah
  • Tisagenlecleucel-T




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. Proportion of patients experiencing response (complete response and partial response) [ Time Frame: Up to 1 year ]
    Estimated with a corresponding 95% confidence interval.



Information from the National Library of Medicine

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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
Criteria

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

Information from the National Library of Medicine

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


Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Ziopharm Oncology
Investigators
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Principal Investigator: Partow Kebriaei M.D. Anderson Cancer Center
Additional Information:
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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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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