Study of CD19 Specific Chimeric Antigen Receptor Positive T Cells (CAR-T) in ALL and NHL

NCT04206943 | Unknown Phase 1

• 1 other identifier: CD19-SP-CAR-T
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

It is a treatment that activates and strengthens the immune system against cancer. Recently, T cell receptors have been genetically rearranged by adaptive T cell therapies, which are promising in the fight against cancer, and are now able to recognize antigens on tumor cells. These modified T cell receptors are called chimeric antigen receptors. Many previous clinical studies have shown that different CAR-T cells are effective in relapse / refractory B cell cancers and NHL.

Conditions

Acute Lymphoblastic Leukemia; Non Hodgkin Lymphoma

Keywords

CAR-T Cell; CD19; ALL; NHL; Cancer; Chimeric Antigen Receptor

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events

  Type, frequency and severity of adverse events (AEs) and laboratory abnormalities.

  6 Months

Secondary Outcomes (15)

• Complete Remission Rate

  3 Months

• Total Response Rate

  3 Months

• Duration of Remission (DOR)

  6 Months

• Relapse Free Survival (RFS)

  6 Months

• Progression Free Survival

  6 Months

Study Arms (2)

A Low Dose

EXPERIMENTAL

4 x 10\^6 Car-T cell/ kg

Biological: Car-T Cell Therapy

B High Dose

EXPERIMENTAL

6 x 10\^6 Car-T cell/ kg

Biological: Car-T Cell Therapy

Interventions

Car-T Cell Therapy BIOLOGICAL

Lymphodepletion Protocol: * -6. Day: Cyclophosphamide 300 mg / m\^2 i.v. * -5. -4. and -3. Days: Fludarabine 30 mg / m\^2 i.v. In addition, one day before the lymphodepletion protocol, xanthine oxidase enzyme inhibitor tablets received 100 mg / day p.o. and 0.9% sodium chloride solution 2000 ml / day i.v. infusion on protocol day received and continues for 2 weeks Car-T cells are administered in 3 split doses. Day 0: 20% or 40% (20% in patients with high tumor burden - in patients with bulky disease and / or more than 15% blast in bone marrow, 40% in patients with low tumor burden) Day 2: 30% or 50%, (the total amount of Car-T cell dose that should be given in the first 2 days should be 70%.) Third dose (%30);is given on the 7th day in the absence of cytokine release syndrome, or if cytokine release syndrome occurs, Car-T cells are given within 1 month if the number of copies falls below 5,000 / ml in 2 consecutive measurements.

A Low Dose; B High Dose

Eligibility Criteria

• Age: 3 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Been diagnosed with CD19 (+) B-Acute lymphoblastic lymphoma or CD19 (+) Non-Hodgkin Lymphoma
• Having a measurable disease
• Relapsed/ refractory (at least 2 cases to the ward; in relapse after autologous transplantation in NHL) disease
• CD19 (+) expression in tumor cells by bone marrow/tissue or peripheral blood flow cytometry for relapse patients in the 3-month before the study period
• Bone marrow relapse after allogenic stem cell transplantation and at least 6 months between CAR-T (ISIKOK-19 ©) cell infusion and stem cell transplantation
• Philadelphia gene + B-ALL patient should have received second line treatment with tyrosine kinase inhibitor (TKI) or the usage of tyrosine kinase inhibitor (TKI) for the patient is contraindicated
• Patient; lack of appropriate donor, complications due to previous stem cell transplantation, or rejection of stem cell transplantation as a treatment option after consultation with a physician, or lack of allogenic stem cell transplantation due to high tumor burden.
• Lack of organ dysfunction:
• Maximum serum creatinine value: 1.7 mg / decilitre (male patients), 1.4 mg / decilitre (female patients)
• Liver function tests are within normal limits
• Bilirubin \<2.0 mg / decilitre
• Central oxygen pressure in room air \> 91% and no dyspnea
• Measurement of left ventricular ejection fraction ≥45% and left ventricular systolic function ≥28% by echocardiography during screening
• Expected survival is ≥ 3 months
• Performance condition: Karnofsky ≥ 50%

You may not qualify if:

• Concomitant history of cardiac, hepatic, neurologic, nephrologic, psychiatric, autoimmune and additional oncological diseases affecting physiological functions
• Life expectancy \<2 months
• Hepatitis B, Hepatitis C, Human immunodeficiency virus infection
• Before CAR-T (ISIKOK-19 ©) cell infusion
• Systemic steroid treatments, tyrosine kinase inhibitors, hydroxyurea, short-acting cytotoxic drugs should be stopped 72 hours before.
• week ago, vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate (if \<25 mg / m\^2), cytosine arabinoside (if \<100 mg / m\^2), asparaginase and intrathecal treatments should be stopped.
• weeks ago, salvage treatments (chemotherapy drugs other than lymphodepletion as part of the protocol, clofarabine, cytosine arabinoside (if\> 100 mg / m\^2), anthracyclines, methotrexate (if ≥25 mg / m\^2), drugs used for graft versus host disease, long-acting growth factors, vincristine, immunomodulatory drugs should be stopped.
• Radiotherapy taken outside the central nervous system should be stopped 2 weeks prior.
• Any systemic treatment with pegylated asparaginase and donor lymphocyte infusion should be stopped 4 weeks prior.
• Anti-t cell therapies containing T cell lysis or toxic antibodies should be stopped 8 weeks before.
• Radiotherapy for the central nervous system should be stopped 8 weeks ago.
• Less than 3 months after stem cell transplantation
• Below 60% in tissue biopsies and / or CD19 expression in tumor cells by flow cytometric analysis in bone marrow is below 85%
• Allergic to drugs that are used at any stage of treatment
• Having received experimental drug treatment in the last month

Sponsors & Collaborators

• Acibadem University: lead
• Acıbadem Atunizade Hospital: collaborator
• The Scientific and Technological Research Council of Turkey: collaborator
• Acıbadem Labcell: collaborator

Study Sites (1)

Acıbadem Labcell Cellular Therapy Laboratories

Istanbul, 34758, Turkey (Türkiye)

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms

Interventions

Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Ercument Ovali, MD

  Director

  STUDY DIRECTOR

Central Study Contacts

Ercument Ovalı, MD

CONTACT

+905325729174; ercument.ovali@acibadem.com

Siret Ratip, MD

CONTACT

+905326873789; siret.ratip@acibadem.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2019
• First Posted: December 20, 2019
• Study Start: October 12, 2019
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: January 27, 2020

Record last verified: 2019-09

Locations

TU (1)