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An Open-label, Multi-center Phase Ib/II Study of CN201 in Subjects With Precursor B-cell Acute Lymphoblastic Leukemia

Primary Purpose

Acute Lymphoblastic Leukemia

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CN201
Sponsored by
Curon Biopharmaceutical (Shanghai) Co.,Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Subjects aged ≥18 years old on the day of signing the ICF.
  2. Subjects with B-ALL (including pro B-, pre B-, common ALL) who have more than 5% blasts in the bone marrow will be enrolled into different cohorts according to the following criteria:

    1. Subjects with Ph-negative B-ALL with any of the following could be enrolled in Phase I and Cohort 1 in Phase II:

      • Refractory to primary induction therapy or salvage therapy
      • Relapse with first remission duration ≤12 months
      • Second or later relapse
      • Relapse after allogeneic HSCT
    2. Subjects with Ph-positive B-ALL who have progressed after or are intolerant to their second (or more) tyrosine kinase inhibitors (TKIs).
  3. Subjects with Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2.
  4. At least 3 months expected survival.
  5. Adequate organ function, further defined as:

    Liver Function Total bilirubin ≤1.5 × upper limit of normal (ULN) Alanine aminotransferase (ALT) ≤3 × ULN Aspartate aminotransferase (AST) ≤3 × ULN Renal Function Serum/plasma creatinine, or Creatinine clearance ≤1.5 × ULN or

    • 50 mL/min (calculated by Cockcroft-Gault formula)
  6. Female subjects must be non-pregnant and non-lactating, and must use an acceptable, highly effective double contraception method from Screening until 90 (±7 days) days after the last dose of CN201.
  7. Subjects must be able to understand and sign the paper ICF before any study-specific procedure is conducted.

Exclusion Criteria:

  1. Subjects with Burkitt's leukemia.
  2. Subjects who have received prior treatment with anti-CD19 therapy within 3 months prior to the first dose of CN201.
  3. Subjects who have received allogeneic HSCT within 12 weeks prior to the first dose of CN201.
  4. Subjects who have received autologous HSCT within 6 weeks prior to the first dose of CN201.
  5. Subjects who have received radiotherapy or chemotherapy within 2 weeks, prior to the first dose of CN201 (except for intrathecal chemotherapy and dexamethasone).
  6. Subjects who have received immunotherapy within 3 weeks prior to the first dose of CN201.
  7. Subjects who have received other investigational agents (not yet approved by any regulatory agency) within 3 weeks prior to the first dose of CN201.
  8. Subjects who have received prior treatment with CAR-T within 3 months prior to the first dose of CN201.
  9. Subjects with major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks prior to the first dose of CN201, or elective surgery during the study.
  10. Subjects who use of live attenuated vaccine within 4 weeks prior to the first dose of CN201

    • Exception: Use of an approved COVID-19 vaccine is allowed, but the last dose of COVID-19 vaccine must be administered at least 2 weeks prior to the first dose of CN201.
    • For active subjects enrolled in this study, COVID-19 vaccination is allowed after 8 weeks treatment have been completed and the safety data have been obtained, to allows conclusions regarding the safety of the CN201.
  11. Subjects with adverse reactions prior to anti-tumor therapy that have not recovered to Grade ≤ 1 assessed by NCI-CTCAE Version 5.0 (except for toxicities such as alopecia judged by the Investigator as no safety risk).
  12. History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
  13. Subjects with clinically symptomatic metastases to the central nervous system (CNS) or meninges, or other evidence of uncontrolled metastases to the CNS or meninges, judged by the Investigator. History CNS leukemia that is controlled with intrathecal therapy is allowed.
  14. Subjects with active infection and in current need of, or likely to need, intravenous anti infective therapy.
  15. Subjects with a history of immunodeficiency, including history of any positive test result for human immunodeficiency virus (HIV) antibody.
  16. Subjects with chronic infection with hepatitis B, defined as having a positive hepatitis B surface antigen (HBsAg) test and/or detectable level of HBV DNA at Screening, or hepatitis C infection, defined as having a positive HCV antibody test.
  17. Subjects with current or previous interstitial lung disease.
  18. Subjects with concomitant secondary malignancies (except adequately treated non melanomatous skin cancers, ductal carcinoma in situ, superficial bladder cancer, prostate cancer, or in situ cervical cancers) are excluded unless a complete remission is achieved at least 5 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
  19. Subjects with a history of serious cardiovascular and cerebrovascular diseases, including but not limited to:

    • Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, degree II-III atrioventricular block, or QTc interval ≥480 ms.
    • Acute coronary syndrome, congestive heart failure, stroke, or other Grade 3 or higher cardiovascular and cerebrovascular events within 6 months prior to the first dose of CN201.
    • New York Heart Association (NYHA) functional class ≥II or left ventricular ejection fraction (LVEF) <50%.
  20. Subjects with uncontrollable third space effusion, as judged by the Investigator.
  21. Subjects with active autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.) or history of autoimmune disease with potential CNS involvement.
  22. Any active acute Graft-versus-Host Disease (GvHD), Grade 2-4 according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment.
  23. Any systemic therapy against GvHD within 2 weeks before start of CN201.
  24. Subjects who have previously received immunotherapy and experienced Grade ≥3 immune-related adverse events (irAEs).
  25. Subjects with known alcohol or drug dependence.
  26. Subjects with mental disorders or other conditions that pose high noncompliance risks in the opinion of the Investigator.
  27. Subjects with any other condition or circumstance that would, in the opinion of the Investigator, make the subject unsuitable for participation in this clinical study.

Sites / Locations

  • Institute of Hematology & Blood Diseases HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CN201

Arm Description

By study design, four planned target CN201 dose levels are600ug, 1200 ug, 2500 ug and 5000 ug. Subjects will receive CN201 by intravenous infusion (IV), once per week, four weeks per treatment cycle.

Outcomes

Primary Outcome Measures

Overall incidence and severity of adverse events measured by NCI-CTCAE 5.0
All AEs will be graded according to NCI-CTCAE Version 5.0.
Incidence of the dose-limiting toxicity
In the present study, the DLT observation period is 28 days following the first dose of CN201 in Cycle 1. All AEs will be graded according to NCI-CTCAE Version 5.0.
The maximum tolerated dose
The MTD will be determined based on the occurrence rate of the DLT. If a DLT is observed in 2 or more of 6 subjects, the MTD will have been exceeded. The MTD is defined as the highest dose in which 1/6 or less subjects experience a DLT. If fewer than 2 of 6 evaluable subjects at the highest dose level tested experience a DLT, this dose level will be declared the maximum administered dose .
The recommended phase II dose
The SMC will be responsible for determining the RP2D, taking into account all safety, efficacy, PK, PD, and ADA data.
The rate of complete response within two cycles of treatment with CN201
Response within the first 2 treatment cycle was assessed. Response was evaluated using imageological diagnosis , and bone marrow biopsy. Complete response is defined as the disappearance of all evidence of disease.

Secondary Outcome Measures

Full Information

First Posted
October 7, 2022
Last Updated
August 30, 2023
Sponsor
Curon Biopharmaceutical (Shanghai) Co.,Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05579132
Brief Title
An Open-label, Multi-center Phase Ib/II Study of CN201 in Subjects With Precursor B-cell Acute Lymphoblastic Leukemia
Official Title
An Open-label, Multi-center Phase Ib/II Study of CN201 in Adult Subjects With Precursor B-cell Acute Lymphoblastic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 30, 2022 (Actual)
Primary Completion Date
February 1, 2024 (Anticipated)
Study Completion Date
December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Curon Biopharmaceutical (Shanghai) Co.,Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
An effective treatment for adults B-ALL represents a significant unmet need. CN201 has demonstrated efficacy in nonclinical models of leukemia .CN201 has a longer half-life, thus long term continuous intravenous infusion is not necessary for clinical use. The present study will be conducted in 2 parts: Phase Ib is a dose findingphase to identify the RP2D. Phase II will allow further evaluation of the safety and efficacy of CN201 at the RP2D.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
113 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CN201
Arm Type
Experimental
Arm Description
By study design, four planned target CN201 dose levels are600ug, 1200 ug, 2500 ug and 5000 ug. Subjects will receive CN201 by intravenous infusion (IV), once per week, four weeks per treatment cycle.
Intervention Type
Drug
Intervention Name(s)
CN201
Intervention Description
During the treatment period, subjects will receive an intravenous (IV) infusion of CN201 once a week (QW) in a 4-week treatment cycle.
Primary Outcome Measure Information:
Title
Overall incidence and severity of adverse events measured by NCI-CTCAE 5.0
Description
All AEs will be graded according to NCI-CTCAE Version 5.0.
Time Frame
through study completion, an average of 1 year
Title
Incidence of the dose-limiting toxicity
Description
In the present study, the DLT observation period is 28 days following the first dose of CN201 in Cycle 1. All AEs will be graded according to NCI-CTCAE Version 5.0.
Time Frame
4 weeks
Title
The maximum tolerated dose
Description
The MTD will be determined based on the occurrence rate of the DLT. If a DLT is observed in 2 or more of 6 subjects, the MTD will have been exceeded. The MTD is defined as the highest dose in which 1/6 or less subjects experience a DLT. If fewer than 2 of 6 evaluable subjects at the highest dose level tested experience a DLT, this dose level will be declared the maximum administered dose .
Time Frame
through study completion, an average of 1 year
Title
The recommended phase II dose
Description
The SMC will be responsible for determining the RP2D, taking into account all safety, efficacy, PK, PD, and ADA data.
Time Frame
through study completion, an average of 1 year
Title
The rate of complete response within two cycles of treatment with CN201
Description
Response within the first 2 treatment cycle was assessed. Response was evaluated using imageological diagnosis , and bone marrow biopsy. Complete response is defined as the disappearance of all evidence of disease.
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects aged ≥18 years old on the day of signing the ICF. Subjects with B-ALL (including pro B-, pre B-, common ALL) who have more than 5% blasts in the bone marrow will be enrolled into different cohorts according to the following criteria: Subjects with Ph-negative B-ALL with any of the following could be enrolled in Phase I and Cohort 1 in Phase II: Refractory to primary induction therapy or salvage therapy Relapse with first remission duration ≤12 months Second or later relapse Relapse after allogeneic HSCT Subjects with Ph-positive B-ALL who have progressed after or are intolerant to their second (or more) tyrosine kinase inhibitors (TKIs). Subjects with Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2. At least 3 months expected survival. Adequate organ function, further defined as: Liver Function Total bilirubin ≤1.5 × upper limit of normal (ULN) Alanine aminotransferase (ALT) ≤3 × ULN Aspartate aminotransferase (AST) ≤3 × ULN Renal Function Serum/plasma creatinine, or Creatinine clearance ≤1.5 × ULN or 50 mL/min (calculated by Cockcroft-Gault formula) Female subjects must be non-pregnant and non-lactating, and must use an acceptable, highly effective double contraception method from Screening until 90 (±7 days) days after the last dose of CN201. Subjects must be able to understand and sign the paper ICF before any study-specific procedure is conducted. Exclusion Criteria: Subjects with Burkitt's leukemia. Subjects who have received prior treatment with anti-CD19 therapy within 3 months prior to the first dose of CN201. Subjects who have received allogeneic HSCT within 12 weeks prior to the first dose of CN201. Subjects who have received autologous HSCT within 6 weeks prior to the first dose of CN201. Subjects who have received radiotherapy or chemotherapy within 2 weeks, prior to the first dose of CN201 (except for intrathecal chemotherapy and dexamethasone). Subjects who have received immunotherapy within 3 weeks prior to the first dose of CN201. Subjects who have received other investigational agents (not yet approved by any regulatory agency) within 3 weeks prior to the first dose of CN201. Subjects who have received prior treatment with CAR-T within 3 months prior to the first dose of CN201. Subjects with major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks prior to the first dose of CN201, or elective surgery during the study. Subjects who use of live attenuated vaccine within 4 weeks prior to the first dose of CN201 Exception: Use of an approved COVID-19 vaccine is allowed, but the last dose of COVID-19 vaccine must be administered at least 2 weeks prior to the first dose of CN201. For active subjects enrolled in this study, COVID-19 vaccination is allowed after 8 weeks treatment have been completed and the safety data have been obtained, to allows conclusions regarding the safety of the CN201. Subjects with adverse reactions prior to anti-tumor therapy that have not recovered to Grade ≤ 1 assessed by NCI-CTCAE Version 5.0 (except for toxicities such as alopecia judged by the Investigator as no safety risk). History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis. Subjects with clinically symptomatic metastases to the central nervous system (CNS) or meninges, or other evidence of uncontrolled metastases to the CNS or meninges, judged by the Investigator. History CNS leukemia that is controlled with intrathecal therapy is allowed. Subjects with active infection and in current need of, or likely to need, intravenous anti infective therapy. Subjects with a history of immunodeficiency, including history of any positive test result for human immunodeficiency virus (HIV) antibody. Subjects with chronic infection with hepatitis B, defined as having a positive hepatitis B surface antigen (HBsAg) test and/or detectable level of HBV DNA at Screening, or hepatitis C infection, defined as having a positive HCV antibody test. Subjects with current or previous interstitial lung disease. Subjects with concomitant secondary malignancies (except adequately treated non melanomatous skin cancers, ductal carcinoma in situ, superficial bladder cancer, prostate cancer, or in situ cervical cancers) are excluded unless a complete remission is achieved at least 5 years prior to study entry and no additional therapy is required or anticipated to be required during the study period. Subjects with a history of serious cardiovascular and cerebrovascular diseases, including but not limited to: Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, degree II-III atrioventricular block, or QTc interval ≥480 ms. Acute coronary syndrome, congestive heart failure, stroke, or other Grade 3 or higher cardiovascular and cerebrovascular events within 6 months prior to the first dose of CN201. New York Heart Association (NYHA) functional class ≥II or left ventricular ejection fraction (LVEF) <50%. Subjects with uncontrollable third space effusion, as judged by the Investigator. Subjects with active autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.) or history of autoimmune disease with potential CNS involvement. Any active acute Graft-versus-Host Disease (GvHD), Grade 2-4 according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment. Any systemic therapy against GvHD within 2 weeks before start of CN201. Subjects who have previously received immunotherapy and experienced Grade ≥3 immune-related adverse events (irAEs). Subjects with known alcohol or drug dependence. Subjects with mental disorders or other conditions that pose high noncompliance risks in the opinion of the Investigator. Subjects with any other condition or circumstance that would, in the opinion of the Investigator, make the subject unsuitable for participation in this clinical study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianxiang Wang, Dr.
Phone
86-022-23909067
Email
wangjx@ihcams.ac.cn
Facility Information:
Facility Name
Institute of Hematology & Blood Diseases Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianxiang Wang, Dr.
Phone
86-022-23909067
Email
wangjx@ihcams.ac.cn
First Name & Middle Initial & Last Name & Degree
Jianxiang Wang, Dr.
First Name & Middle Initial & Last Name & Degree
Ying Wang, Dr.

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

An Open-label, Multi-center Phase Ib/II Study of CN201 in Subjects With Precursor B-cell Acute Lymphoblastic Leukemia

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