Treatment of Hematological Malignancy With Novel CAR-T Cells.

Adoptive Immunotherapy for Hematological Malignancy With Novel CAR-T Cells.

This is a single arm, open-label, early phase I study, to determine the safety and efficacy of Novel CAR-T cell therapy in Hematological Malignancy treatment.

Study Overview

• Status: Unknown
• Conditions: Multiple Myeloma; B-cell Acute Lymphoblastic Leukemia; B-cell Non Hodgkin Lymphoma
• Intervention / Treatment: Biological: Novel CAR-T

Detailed Description

The Novel CAR-T contains either a scFv plus a PD-L1 blocker, or two scFvs, in a cytokine complex based outer memberane structure, this kind of structure enables the CAR-T cells to simultaneously target one or two targets on the tumor cell surface and enhance CAR-T cell persistence in tumor microenvironment，as well as stimulating innate T/NK cell activation and expansion.

• Study Type: Interventional
• Enrollment (Anticipated): 9
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410005
      • Recruiting
      • Hunan Provincial People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. All subjects must personally sign and date the consent form before initiating any study specific procedures or activities;
2. All subjects must be able to comply with all the scheduled procedures in the study;
3. Clear diagnosis of hematological malignancy, including B-cell Non-Hodgkin lymphoma, B-cell lymphoblastic leukemia, multiple myeloma.
4. Fufill one or more of the following criteria: Relapsed after most recent therapy; Progressive disease in standard chemotherapy; Disease progression or relapsed after ASCT;
5. At least one clear indicator for hematological malignancy monitoring;
6. Aged <70 years;
7. Expected survival ≥12 weeks;
8. Eastern cooperative oncology group (ECOG) performance status of≤3;
9. Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks;

10. All other treatment induced adverse events must have been resolved to

    ≤grade 1;

11. Laboratory tests must fulfill the following criteria: ANC ≥ 1000/uL, HGB>70g/L, Platelet count ≥ 50,000/uL, Creatinine clearance ≤1.5 ULN, Serum ALT/AST ≤2.5 ULN, Total bilirubin ≤1.5 ULN (except in subjects with Gilbert's syndrome);

Exclusion Criteria:

1. Presence of fungal, bacterial, viral, or other infection that is hardly to control (defined by investigator);
2. Patients with symptomatic central nervous system metastasis, intracranial metastasis, and cancer cells found in cerebrospinal fluid are not recommended to participate in this study. Symptom free or post-treatment stable disease or disappearance of lesions should not be excluded. The specific selection is ultimately determined by the investigator;
3. Lactating women or women of childbearing age who plan to conceive during the investigational time period;
4. Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive);
5. Known history of infection with HIV;
6. Subjects need systematic usage of corticosteroid;
7. Subjects need systematic usage of immunosuppressive drug;
8. Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study;
9. Other reasons the investigator consider the patient may not be suitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Novel CAR-T; Novel CAR-T cells will be administered intravenously	Biological: Novel CAR-T; A conditioning chemotherapy regimen of fludarabine and cyclophosphamide may be administered, followed by a single infusion of Novel CAR-T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety (Incidence of treatment-related adverse events as assessed by CTCAE v4.03)	Incidence of treatment-related adverse events as assessed by CTCAE v4.03	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)	Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma	3 months
Partial response rate [PR] (Partial response rate per the revised International Working Group (IWG) Response Criteria)	Partial response rate per the revised International Working Group (IWG) Response Criteria	3 months
Duration of Response (The time from response to relapse or progression)	The time from response to relapse or progression	24 months
Progression Free Survival (The time from the first day of treatment to the date on which disease progresses)	The time from the first day of treatment to the date on which disease progresses	24 months
Overall Survival (The number of patient alive, with or without signs of cancer)	The number of patient alive, with or without signs of cancer	24 months

Collaborators and Investigators

• Sponsor: Timmune Biotech Inc.
• Collaborators: Hunan Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Anticipated): August 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: December 6, 2019
• First Submitted That Met QC Criteria: December 6, 2019
• First Posted (Actual): December 10, 2019

Study Record Updates

• Last Update Posted (Actual): December 10, 2019
• Last Update Submitted That Met QC Criteria: December 6, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: CD19-TriCAR-T; 1922-TriCAR-T; BCMA-TriCAR-T
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Neoplasms by Site; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Leukemia, Lymphoid; Leukemia; Lymphoma; Lymphoma, B-Cell; Hematologic Neoplasms; Multiple Myeloma; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: 2019-24.1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No