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A Study of CT-RD06 Cell Injection in Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancy

Primary Purpose

Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma

Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
CT-RD06
Sponsored by
He Huang
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia

Eligibility Criteria

3 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Inclusion criteria only for B-ALL:

    1. Male or female aged 3-70 years;
    2. Histologically confirmed diagnosis of CD19+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);
    3. Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):

      1. CR not achieved after standardized chemotherapy;
      2. CR achieved following the first induction, but CR duration is ≤ 12 months;
      3. Ineffectively after first or multiple remedial treatments;
      4. 2 or more relapses;
    4. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is﹥5% (by morphology), and/or﹥1% (by flow cytometry);
    5. Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments;
  • Inclusion criteria only for B-NHL:

    1. Male or female aged 18-70 years;
    2. Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHO Classification Criteria for Lymphoma (2016);
    3. Relapsed or refractory B-NHL (meeting one of the following conditions):

      1. No response or relapse after second-line or above chemotherapy regimens;
      2. Primary drug resistance;
      3. Relapse after auto-HSCT;
    4. At least one assessable tumor lesion per Lugano 2014 criteria;
  • Common inclusion criteria for B-ALL and B-NHL:

    1. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L;
    2. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
    3. No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%;
    4. Estimated survival time ≥ 3 months;
    5. ECOG performance status 0 to 2;
    6. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

  • Inclusion exclusion criteria only for B-ALL:

    1. Extramedullary lesions, except that CNSL (CNS-1) has been effectively controlled;
    2. Confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, Burkitt's leukemia/ lymphoma per WHO Classification Criteria;
    3. Hereditary syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome;
  • Inclusion exclusion criteria only for B-NHL:

    1. Extranodal lesions in the brain (tumor cells in CSF, and/or MRI shows invasion of intracranial lymphoma);
    2. Extensive invasion of gastrointestinal lymphoma;
  • Common exclusion criteria for B-ALL and B-NHL:

    1. History of hypersensitivity to any component of cell product;
    2. Prior treatment with any CAR T cell product or other genetically-modified T cell therapies;
    3. Prior treatment with radiotherapy, chemotherapy or mAb 1 week prior to apheresis;
    4. New York Heart Associate (NYHA) Class III/IV cardiac insufficiency (see Appendix 1);
    5. Myocardial infarction, cardioangioplasty or stenting, unstable angina pectoris, or other severe cardiac diseases within 12 months of enrollment;
    6. Severe primary or secondary hypertension of grade 3 or above (WHO Hypertension Guidelines, 1999);
    7. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
    8. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
    9. Severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
    10. Indwelling catheters in vivo (e.g. percutaneous nephrostomy, Foley catheter, bile duct catheter, or pleural/peritoneal/pericardial catheter). Ommaya storage, dedicated central venous access catheters such as Port-a-Cath or Hickman catheters are allowed;
    11. History of other primary cancer, except for the following conditions:

      1. Cured non-melanoma after resection, such as basal cell carcinoma of the skin;
      2. Cervical cancer in situ, localized prostate cancer, ductal cancer in situ with disease-free survival ≥ 2 years after adequate treatment;
    12. Autoimmune diseases requiring treatment, immunodeficiency or patients requiring immunosuppressive therapy;
    13. Prior immunizations with live vaccine 4 weeks prior to screening;
    14. History of alcoholism, drug abuse or mental illness;
    15. If HBsAg positive at screening, HBV DNA copy number detected by PCR in patients with active hepatitis B > 1000 (if HBV DNA copy number≤1000, routine antiviral therapy is required after enrollment), as well as CMV, hepatitis C, syphilis and HIV infection;
    16. Concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids;
    17. Patients who have participated in any other clinical studies within 2 weeks prior to screening;
    18. Female pregnant or lactating, male for female fertile but unable to take medically acceptable contraception measures;
    19. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

Sites / Locations

  • The First Hospital of Zhejiang Medical Colleage Zhejiang UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Administration of CT-RD06

Arm Description

Dose escalation follows the standard 3+3 dose escalation design. A total of 3 dose levels are set for subjects.

Outcomes

Primary Outcome Measures

Dose-limiting toxicity (DLT)
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs)
Incidence of treatment-emergent adverse events [Safety and Tolerability]

Secondary Outcome Measures

B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR)
Assessment of ORR (ORR = CR + CRi ) at Month 6, 12, 18 and 24
B-ALL, Overall survival (OS)
From the first infusion of CT-RD06 to death or the last visit
B-ALL, Event-free survival (EFS)
From the first infusion of CT-RD06 to the occurrence of any event, including death, relapse or gene relapse, disease progression (any one occurs first), and the last visit
B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR)
Assessment of ORR (ORR = CR + PR) per Lugano 2014 criteria
B-NHL, disease control rate (DCR)
Assessment of DCR (DCR=CR+PR+SD) per Lugano 2014 criteria

Full Information

First Posted
January 8, 2020
Last Updated
February 19, 2020
Sponsor
He Huang
Collaborators
Nanjing Bioheng Biotech Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04226989
Brief Title
A Study of CT-RD06 Cell Injection in Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancy
Official Title
A Study of CT-RD06 Cell Injection in Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancy
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Recruiting
Study Start Date
February 5, 2020 (Actual)
Primary Completion Date
February 5, 2022 (Anticipated)
Study Completion Date
May 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
He Huang
Collaborators
Nanjing Bioheng Biotech Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A study of CT-RD06 cell injection in patients with relapsed or refractory CD19+ B-cell hematological malignancy.
Detailed Description
This is a single arm, open-label, single-center study. This study is indicated for relapsed or refractory CD19+ B-cell hematological malignancy: B-ALL and B-NHL, the selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 2 groups of patients will be enrolled, 36 in each group. Primary objective is to explore the safety, main consideration is dose-related safety.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Administration of CT-RD06
Arm Type
Experimental
Arm Description
Dose escalation follows the standard 3+3 dose escalation design. A total of 3 dose levels are set for subjects.
Intervention Type
Biological
Intervention Name(s)
CT-RD06
Other Intervention Name(s)
CT-RD06 CAR-T cell injection
Intervention Description
CT-RD06 cell injection by intravenous infusion
Primary Outcome Measure Information:
Title
Dose-limiting toxicity (DLT)
Description
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Time Frame
Baseline up to 28 days after CT-RD06 infusion
Title
Incidence of treatment-emergent adverse events (TEAEs)
Description
Incidence of treatment-emergent adverse events [Safety and Tolerability]
Time Frame
Up to 2 years after CT-RD06 infusion
Secondary Outcome Measure Information:
Title
B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR)
Description
Assessment of ORR (ORR = CR + CRi ) at Month 6, 12, 18 and 24
Time Frame
At Month 1, 3, 6, 12, 18 and 24
Title
B-ALL, Overall survival (OS)
Description
From the first infusion of CT-RD06 to death or the last visit
Time Frame
Up to 2 years after CT-RD06 infusion
Title
B-ALL, Event-free survival (EFS)
Description
From the first infusion of CT-RD06 to the occurrence of any event, including death, relapse or gene relapse, disease progression (any one occurs first), and the last visit
Time Frame
Up to 2 years after CT-RD06 infusion
Title
B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR)
Description
Assessment of ORR (ORR = CR + PR) per Lugano 2014 criteria
Time Frame
At Week 4, 12, and Month 6, 12, 18, 24
Title
B-NHL, disease control rate (DCR)
Description
Assessment of DCR (DCR=CR+PR+SD) per Lugano 2014 criteria
Time Frame
At Week 12 and Month 6, 12, 18, 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Inclusion criteria only for B-ALL: Male or female aged 3-70 years; Histologically confirmed diagnosis of CD19+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1); Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions): CR not achieved after standardized chemotherapy; CR achieved following the first induction, but CR duration is ≤ 12 months; Ineffectively after first or multiple remedial treatments; 2 or more relapses; The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is﹥5% (by morphology), and/or﹥1% (by flow cytometry); Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments; Inclusion criteria only for B-NHL: Male or female aged 18-70 years; Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHO Classification Criteria for Lymphoma (2016); Relapsed or refractory B-NHL (meeting one of the following conditions): No response or relapse after second-line or above chemotherapy regimens; Primary drug resistance; Relapse after auto-HSCT; At least one assessable tumor lesion per Lugano 2014 criteria; Common inclusion criteria for B-ALL and B-NHL: Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L; Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%; No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%; Estimated survival time ≥ 3 months; ECOG performance status 0 to 2; Patients or their legal guardians volunteer to participate in the study and sign the informed consent. Exclusion Criteria: Inclusion exclusion criteria only for B-ALL: Extramedullary lesions, except that CNSL (CNS-1) has been effectively controlled; Confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, Burkitt's leukemia/ lymphoma per WHO Classification Criteria; Hereditary syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome; Inclusion exclusion criteria only for B-NHL: Extranodal lesions in the brain (tumor cells in CSF, and/or MRI shows invasion of intracranial lymphoma); Extensive invasion of gastrointestinal lymphoma; Common exclusion criteria for B-ALL and B-NHL: History of hypersensitivity to any component of cell product; Prior treatment with any CAR T cell product or other genetically-modified T cell therapies; Prior treatment with radiotherapy, chemotherapy or mAb 1 week prior to apheresis; New York Heart Associate (NYHA) Class III/IV cardiac insufficiency (see Appendix 1); Myocardial infarction, cardioangioplasty or stenting, unstable angina pectoris, or other severe cardiac diseases within 12 months of enrollment; Severe primary or secondary hypertension of grade 3 or above (WHO Hypertension Guidelines, 1999); Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past; History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases; Severe active infections (excluding simple urinary tract infection and bacterial pharyngitis); Indwelling catheters in vivo (e.g. percutaneous nephrostomy, Foley catheter, bile duct catheter, or pleural/peritoneal/pericardial catheter). Ommaya storage, dedicated central venous access catheters such as Port-a-Cath or Hickman catheters are allowed; History of other primary cancer, except for the following conditions: Cured non-melanoma after resection, such as basal cell carcinoma of the skin; Cervical cancer in situ, localized prostate cancer, ductal cancer in situ with disease-free survival ≥ 2 years after adequate treatment; Autoimmune diseases requiring treatment, immunodeficiency or patients requiring immunosuppressive therapy; Prior immunizations with live vaccine 4 weeks prior to screening; History of alcoholism, drug abuse or mental illness; If HBsAg positive at screening, HBV DNA copy number detected by PCR in patients with active hepatitis B > 1000 (if HBV DNA copy number≤1000, routine antiviral therapy is required after enrollment), as well as CMV, hepatitis C, syphilis and HIV infection; Concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids; Patients who have participated in any other clinical studies within 2 weeks prior to screening; Female pregnant or lactating, male for female fertile but unable to take medically acceptable contraception measures; Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.
Facility Information:
Facility Name
The First Hospital of Zhejiang Medical Colleage Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
He Huang, MD
Phone
86-13605714822
Email
hehuangyuzj@163.com
First Name & Middle Initial & Last Name & Degree
Jimin Shi, MD
Phone
86-13857119907
Email
jiminshi@126.com
First Name & Middle Initial & Last Name & Degree
He Huang, MD

12. IPD Sharing Statement

Learn more about this trial

A Study of CT-RD06 Cell Injection in Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancy

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