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

April 7, 2024 updated by: Antengene Corporation

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)

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Estimated)

84

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Chongqing
      • Chongqing, Chongqing, China, 400038
        • Not yet recruiting
        • The Second Affiliated Hospital of PLA Army Medical University
        • Contact:
          • Xi Zhang, PhD
        • Principal Investigator:
          • Xi Zhang, PhD
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Sun Yat-Sen University Cancer Center
        • Contact:
          • Zhiming Li, PhD
        • Principal Investigator:
          • Zhiming Li, PhD
    • Henan
      • Zhengzhou, Henan, China, 450003
        • Recruiting
        • Henan Cancer Hospital
        • Contact:
          • Lina Zhang, PhD
        • Principal Investigator:
          • Lina Zhang, PD
    • Hubei
      • Wuhan, Hubei, China, 430022
        • Recruiting
        • Wuhan Union Hospital
        • Contact:
          • Liling Zhang, PhD
        • Principal Investigator:
          • Liling Zhang, PhD
    • Liaoning
      • Shenyang, Liaoning, China, 110001
        • Not yet recruiting
        • The First Affiliated Hospital of China Medical University
        • Contact:
          • Xiaojing Yan, PhD
        • Principal Investigator:
          • Xiaojing Yan, PhD
    • Shanghai
      • Shanghai, Shanghai, China, 200025
        • Not yet recruiting
        • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
        • Contact:
        • Principal Investigator:
          • Weilin Zhao, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ATG-010
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
Drug: ATG-010
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
Other Names:
  • Selinexor
Drug: Lenalidomide
Oral administration,QD, Days 1-21 of each cycle
Drug: Rituximab
Intravenous injection Days 1 of each cycle, Cycles 1-6

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DLT
Time Frame: 28 days after administration
The occurrence of severe toxicities during the first cycle of systemic cancer therapy
28 days after administration
AE
Time Frame: 28 days after administration
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.
28 days after administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ORR
Time Frame: One year after last patient first dose
Percentage of subjects with PR, or CR
One year after last patient first dose
PFS
Time Frame: One year after last patient first dose
Duration of time from the first dose of study drug until progression or death due to any cause
One year after last patient first dose
DOR
Time Frame: One year after last patient first dose
Duration of time from first occurrence of CR or PR until the first date that disease
One year after last patient first dose
OS
Time Frame: One year after last patient first dose
Duration of time from the first dose of study drug until death due to any cause
One year after last patient first dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Antengene Corporation

Investigators

  • Study Director: Lily Pei, MA.Sc, Medical Monitor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 7, 2022

Primary Completion (Estimated)

March 7, 2025

Study Completion (Estimated)

June 7, 2025

Study Registration Dates

First Submitted

February 9, 2022

First Submitted That Met QC Criteria

March 2, 2022

First Posted (Actual)

March 4, 2022

Study Record Updates

Last Update Posted (Actual)

April 9, 2024

Last Update Submitted That Met QC Criteria

April 7, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ATG-010-B-NHL-002

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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