Clinical Trial: NCT02529813 - My Cancer Genome

NCT02529813

Description:

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.

Related Conditions:

Acute Biphenotypic Leukemia
Acute Lymphoblastic Leukemia
Chronic Lymphocytic Leukemia
Non-Hodgkin Lymphoma
Small Lymphocytic Lymphoma

Recruiting Status:

Active, not recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02529813

Trial Eligibility

Document

Title

Brief Title: CD19-Specific T-cells in Treating Patients With Advanced Lymphoid Malignancies
Official Title: CD19+ Chimeric Antigen Receptor T Cells for Patients With Advanced Lymphoid Malignancies

Clinical Trial IDs

ORG STUDY ID: 2013-1018
SECONDARY ID: NCI-2015-01492
SECONDARY ID: 20152145
SECONDARY ID: 1159157
SECONDARY ID: 2013-1018
SECONDARY ID: P30CA016672
NCT ID: NCT02529813

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

Interventions

Drug	Synonyms	Arms
Cyclophosphamide	(-)-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	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)
Tisagenlecleucel	CART-19, CART19, CTL019, CTL019 T-cells, Kymriah, Tisagenlecleucel-T	Arm I (CD19 positive chimeric antigen receptor T-cells)

Purpose

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.

Trial Arms

Name	Type	Description	Interventions
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.	Cyclophosphamide Fludarabine Phosphate Tisagenlecleucel

Eligibility 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

Maximum Eligible Age:	80 Years
Minimum Eligible Age:	1 Year
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Maximum tolerated dose of genetically modified, CD19-specified T cells
Time Frame:	Up to 30 days
Safety Issue:
Description:	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

Measure:	The proportion of patients for which a T cell product could not be prepared
Time Frame:	Up to 1 year
Safety Issue:
Description:	Computed with a corresponding 95% confidence interval.

Measure:	Proportion of patients experiencing response (complete response and partial response)
Time Frame:	Up to 1 year
Safety Issue:
Description:	Estimated with a corresponding 95% confidence interval.

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Active, not recruiting
Lead Sponsor:	M.D. Anderson Cancer Center

Last Updated

July 24, 2019

Clinical Trials /

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