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A Study of ATG-010 in Combination With Lenalidomide and Rituximab (R2) in Adults With DLBCL and iNHL (SWATCH)

Primary Purpose

Diffuse Large B-cell Lymphoma, Indolent Non-Hodgkin Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
ATG-010
Lenalidomide
Rituximab
Sponsored by
Antengene Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-cell Lymphoma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥18 years.
  2. Pathologically confirmed DLBCL (including de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma [e.g., follicular lymphoma]) or B-cell iNHL with histological subtype limited to FL Grade 1, Grade 2, or Grade 3a or nodal or extranodal marginal zone lymphoma (MZL), based on criteria established by the World Health Organization (WHO) 2016 classification.
  3. Received at least 1 line of systemic therapy for the treatment of B-NHL.
  4. Have evidence of relapse or refractory disease.
  5. At least one bi-dimensionally measurable lesion per the Lugano 2014 Criteria (Cheson, 2014; Appendix 4).
  6. Adequate bone marrow function at screening, defined as:

(1) absolute neutrophil count (ANC) ≥1.0 × 109/L (without hematopoietic stimulators such as granulocyte or granulocyte-macrophage colony stimulating factor within 7 days prior to testing); (2) Platelet count ≥75 × 109/L; or ≥50 × 109/L when lymphoma infiltrates bone marrow (without platelet transfusion or TPO, IL-11 and other hematopoietic stimulating factors administration within 7 days prior to testing); (3) Hemoglobin ≥80 g/L (without red blood cell transfusion or hematopoietic stimulating factor such as TPO administration within 14 days prior to testing).

7. Adequate liver and kidney function, defined as:

  1. Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5 × upper limit of normal (ULN);
  2. Serum total bilirubin ≤1.5 × ULN, or ≤3 ULN if have Gilbert syndrome;
  3. Calculated creatinine clearance (CrCl) ≥60 mL/min for Dose Escalation Phase, and ≥30 mL/min for Dose Expansion Phase, based on Cockcroft-Gault formula.

8. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. 9. Agree to effective contraception during the study and within 12 months after the last dose of study treatment.

Exclusion Criteria:

  1. DLBCL with MALT lymphoma; composite lymphoma (Hodgkin's lymphoma+NHL); primary mediastinal (thymic) large B-cell lymphoma; Grade 3b follicular lymphoma.
  2. Dose Escalation Phase: Subjects with known central nervous system involvement. Dose Expansion Phanse: Subjects with advanced lymphoma of the central nervous system involvement at screening, however, subjects have stable central nervous system lymphoma (in the case of no intracranial pressure or other conditions need medical intervention) or do not occur disease progression as assessed by neurological symptoms, signs, and radiography within 28 days prior to C1D1, will be considered eligible.
  3. Previous treatment with ATG-010 (selinexor) or other XPO1 inhibitors, or prior exposure to lenalidomide within 3 months before C1D1.
  4. Contraindication to any drug in the combination therapy of SR2.
  5. Use of any standard or experimental anti B-NHL therapy <21 days prior to C1D1, including chemotherapy, immunotherapy, radio-immunotherapy, nonpalliative radiation, or any other anticancer therapy.
  6. Major surgery, or live vaccines received <28 days prior to C1D1.
  7. ASCT <6 months or CAR-T cell infusion <6 months prior to the screening.
  8. History of allogeneic hematopoietic stem cell transplant.
  9. Any AE related with prior B-NHL treatment had not recovered to ≤Grade 1 (CTCAE, v5.0) or baseline at Screening (except alopecia, AE related to hematology and blood biochemistry; the values of hematology and biochemistry refer to inclusion criteria 7 and 8).
  10. Have active hepatitis B virus (HBV), hepatitis C virus (HCV) infections at screening.
  11. Known serum HIV antibody positive or history of active HIV infection.
  12. Active infection requiring intravenous antibiotics, antivirals, or antifungals treatment within 14 days prior to C1D1; however, prophylactic use of these agents is acceptable (including intravenous medication).
  13. Prior malignancy that required treatment or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) within the 2 years prior to C1D1.
  14. Ischemic or hemorrhagic cerebrovascular disease, or gastrointestinal hemorrhage ≥Grade 3 (CTCAE, v5.0) within 6 months prior to screening.
  15. History of deep vein thrombosis or pulmonary embolism within 12 months prior to screening.
  16. Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal disease or dysfunction that could interfere with absorption of study treatment.
  17. Inability or unwillingness to sign an ICF.
  18. Existed any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety, or being compliant with the study procedures.

Sites / Locations

  • The Second Affiliated Hospital of PLA Army Medical University
  • Sun Yat-Sen University Cancer CenterRecruiting
  • Henan Cancer HospitalRecruiting
  • Wuhan Union HospitalRecruiting
  • The first Affiliated Hospital of China medical University
  • Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ATG-010

Arm Description

Enrolled patients will be treated with dosage groups. Dosage group 1:40mg/time, dosage group 2:60mg/time, dosage group 3:80mg/time; The treatment period was 28 days. The drug was administered on day 1,8 and 15 of each cycle

Outcomes

Primary Outcome Measures

DLT
The occurrence of severe toxicities during the first cycle of systemic cancer therapy
AE
Any adverse medical event that occurs after a patient or clinical trial subject receives a drug product, but is not necessarily related to the treatment.

Secondary Outcome Measures

ORR
Percentage of subjects with PR, or CR
PFS
Duration of time from the first dose of study drug until progression or death due to any cause
DOR
Duration of time from first occurrence of CR or PR until the first date that disease
OS
Duration of time from the first dose of study drug until death due to any cause

Full Information

First Posted
February 9, 2022
Last Updated
February 23, 2023
Sponsor
Antengene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT05265975
Brief Title
A Study of ATG-010 in Combination With Lenalidomide and Rituximab (R2) in Adults With DLBCL and iNHL
Acronym
SWATCH
Official Title
A Single-arm, Phase Ⅰ/Ⅱ Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of ATG-010 in Combination With Lenalidomide and Rituximab (R2) in Adult Patients With Relapsed/Refractory DLBCL and iNHL Who Are Ineligible for High-dose Chemotherapy (HDC) or Autologous Stem Cell Transplant (ASCT)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 7, 2022 (Actual)
Primary Completion Date
March 7, 2025 (Anticipated)
Study Completion Date
June 7, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Antengene Corporation

4. Oversight

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

5. Study Description

Brief Summary
A Single-arm, Phase Ⅰ/Ⅱ Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of ATG-010 in Combination with Lenalidomide and Rituximab (R2) in Adult Patients with Relapsed/Refractory DLBCL and iNHL Who are Ineligible for High-dose Chemotherapy (HDC) or Autologous Stem Cell Transplant (A SCT).
Detailed Description
A Single-arm, Phase Ⅰ/Ⅱ Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of ATG-010 in Combination with Lenalidomide and Rituximab (R2) in Adult Patients with Relapsed/Refractory DLBCL and iNHL Who are Ineligible for High-dose Chemotherapy (HDC) or Autologous Stem Cell Transplant (ASCT).About 84 subjects are scheduled to be enrolled in the study,Maximum 24 (Dose Escalation Phase) and 60 (Dose Expansion Phase).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-cell Lymphoma, Indolent Non-Hodgkin Lymphoma

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
84 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ATG-010
Arm Type
Experimental
Arm Description
Enrolled patients will be treated with dosage groups. Dosage group 1:40mg/time, dosage group 2:60mg/time, dosage group 3:80mg/time; The treatment period was 28 days. The drug was administered on day 1,8 and 15 of each cycle
Intervention Type
Drug
Intervention Name(s)
ATG-010
Other Intervention Name(s)
Selinexor
Intervention Description
Tablets,20mg, once a week: dosage group 1:40mg/time, dosage group 2:60mg/time, dosage group 3:80mg/time The treatment period was 28 days. The drug was administered on day 1,8 and 15 of each cycle
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
Oral administration,QD, Days 1-21 of each cycle
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Intravenous injection Days 1 of each cycle, Cycles 1-6
Primary Outcome Measure Information:
Title
DLT
Description
The occurrence of severe toxicities during the first cycle of systemic cancer therapy
Time Frame
28 days after administration
Title
AE
Description
Any adverse medical event that occurs after a patient or clinical trial subject receives a drug product, but is not necessarily related to the treatment.
Time Frame
28 days after administration
Secondary Outcome Measure Information:
Title
ORR
Description
Percentage of subjects with PR, or CR
Time Frame
One year after last patient first dose
Title
PFS
Description
Duration of time from the first dose of study drug until progression or death due to any cause
Time Frame
One year after last patient first dose
Title
DOR
Description
Duration of time from first occurrence of CR or PR until the first date that disease
Time Frame
One year after last patient first dose
Title
OS
Description
Duration of time from the first dose of study drug until death due to any cause
Time Frame
One year after last patient first dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥18 years. Pathologically confirmed DLBCL (including de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma [e.g., follicular lymphoma]) or B-cell iNHL with histological subtype limited to FL Grade 1, Grade 2, or Grade 3a or nodal or extranodal marginal zone lymphoma (MZL), based on criteria established by the World Health Organization (WHO) 2016 classification. Received at least 1 line of systemic therapy for the treatment of B-NHL. Have evidence of relapse or refractory disease. At least one bi-dimensionally measurable lesion per the Lugano 2014 Criteria (Cheson, 2014; Appendix 4). Adequate bone marrow function at screening, defined as: (1) absolute neutrophil count (ANC) ≥1.0 × 109/L (without hematopoietic stimulators such as granulocyte or granulocyte-macrophage colony stimulating factor within 7 days prior to testing); (2) Platelet count ≥75 × 109/L; or ≥50 × 109/L when lymphoma infiltrates bone marrow (without platelet transfusion or TPO, IL-11 and other hematopoietic stimulating factors administration within 7 days prior to testing); (3) Hemoglobin ≥80 g/L (without red blood cell transfusion or hematopoietic stimulating factor such as TPO administration within 14 days prior to testing). 7. Adequate liver and kidney function, defined as: Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5 × upper limit of normal (ULN); Serum total bilirubin ≤1.5 × ULN, or ≤3 ULN if have Gilbert syndrome; Calculated creatinine clearance (CrCl) ≥60 mL/min for Dose Escalation Phase, and ≥30 mL/min for Dose Expansion Phase, based on Cockcroft-Gault formula. 8. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. 9. Agree to effective contraception during the study and within 12 months after the last dose of study treatment. Exclusion Criteria: DLBCL with MALT lymphoma; composite lymphoma (Hodgkin's lymphoma+NHL); primary mediastinal (thymic) large B-cell lymphoma; Grade 3b follicular lymphoma. Dose Escalation Phase: Subjects with known central nervous system involvement. Dose Expansion Phanse: Subjects with advanced lymphoma of the central nervous system involvement at screening, however, subjects have stable central nervous system lymphoma (in the case of no intracranial pressure or other conditions need medical intervention) or do not occur disease progression as assessed by neurological symptoms, signs, and radiography within 28 days prior to C1D1, will be considered eligible. Previous treatment with ATG-010 (selinexor) or other XPO1 inhibitors, or prior exposure to lenalidomide within 3 months before C1D1. Contraindication to any drug in the combination therapy of SR2. Use of any standard or experimental anti B-NHL therapy <21 days prior to C1D1, including chemotherapy, immunotherapy, radio-immunotherapy, nonpalliative radiation, or any other anticancer therapy. Major surgery, or live vaccines received <28 days prior to C1D1. ASCT <6 months or CAR-T cell infusion <6 months prior to the screening. History of allogeneic hematopoietic stem cell transplant. Any AE related with prior B-NHL treatment had not recovered to ≤Grade 1 (CTCAE, v5.0) or baseline at Screening (except alopecia, AE related to hematology and blood biochemistry; the values of hematology and biochemistry refer to inclusion criteria 7 and 8). Have active hepatitis B virus (HBV), hepatitis C virus (HCV) infections at screening. Known serum HIV antibody positive or history of active HIV infection. Active infection requiring intravenous antibiotics, antivirals, or antifungals treatment within 14 days prior to C1D1; however, prophylactic use of these agents is acceptable (including intravenous medication). Prior malignancy that required treatment or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) within the 2 years prior to C1D1. Ischemic or hemorrhagic cerebrovascular disease, or gastrointestinal hemorrhage ≥Grade 3 (CTCAE, v5.0) within 6 months prior to screening. History of deep vein thrombosis or pulmonary embolism within 12 months prior to screening. Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal disease or dysfunction that could interfere with absorption of study treatment. Inability or unwillingness to sign an ICF. Existed any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety, or being compliant with the study procedures.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hongwei Li, MA.Sc
Phone
021-32501095
Email
felix.li@antengene.com
First Name & Middle Initial & Last Name or Official Title & Degree
Austin Wang, MA.Sc
Email
Austin.wang@antengene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lily Pei, MA.Sc
Organizational Affiliation
Medical Monitor
Official's Role
Study Director
Facility Information:
Facility Name
The Second Affiliated Hospital of PLA Army Medical University
City
Chongqing
State/Province
Chongqing
ZIP/Postal Code
400038
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xi Zhang, PhD
First Name & Middle Initial & Last Name & Degree
Xi Zhang, PhD
Facility Name
Sun Yat-Sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhiming Li, PhD
First Name & Middle Initial & Last Name & Degree
Zhiming Li, PhD
Facility Name
Henan Cancer Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450003
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lina Zhang, PhD
First Name & Middle Initial & Last Name & Degree
Lina Zhang, PD
Facility Name
Wuhan Union Hospital
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430022
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liling Zhang, PhD
First Name & Middle Initial & Last Name & Degree
Liling Zhang, PhD
Facility Name
The first Affiliated Hospital of China medical University
City
Shenyang
State/Province
Liaoning
ZIP/Postal Code
110001
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaojing Yan, PhD
First Name & Middle Initial & Last Name & Degree
Xiaojing Yan, PhD
Facility Name
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weilin Zhao, PhD
Email
Zwl_trial@163.com
First Name & Middle Initial & Last Name & Degree
Weilin Zhao, PhD

12. IPD Sharing Statement

Learn more about this trial

A Study of ATG-010 in Combination With Lenalidomide and Rituximab (R2) in Adults With DLBCL and iNHL

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