Combination treatment for adults with certain types of lymphoma

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)

This study is testing a new combination treatment for adults with certain types of lymphoma who can't have high-dose chemotherapy to see if it helps them feel better.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 84 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Antengene Corporation (Industry-sponsored)
• Drugs / interventions: CAR-T, chemotherapy, immunotherapy, radiation, Rituximab
• Locations: 6 sites (Chongqing, Chongqing and 5 other locations)
• Trial ID: NCT05265975 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, tolerability, and preliminary efficacy of ATG-010 in combination with Lenalidomide and Rituximab in adults with relapsed or refractory Diffuse Large B-cell Lymphoma (DLBCL) and indolent Non-Hodgkin Lymphoma (iNHL) who cannot undergo high-dose chemotherapy or autologous stem cell transplant. It is a single-arm, Phase 1/2 study aiming to enroll approximately 84 participants, with a focus on dose escalation and expansion phases. The study will assess the treatment's effectiveness based on measurable disease criteria.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with relapsed or refractory DLBCL or specific subtypes of iNHL who have previously received systemic therapy.

Not a fit: Patients who are not eligible for this study include those who have not received prior systemic therapy or those with conditions that allow for high-dose chemotherapy or autologous stem cell transplant.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat lymphomas.

How similar studies have performed: While this approach is being evaluated in this specific combination, similar studies have shown promise in treating lymphomas with targeted therapies.

Eligibility criteria

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.

Where this trial is running

Chongqing, Chongqing and 5 other locations

• The Second Affiliated Hospital of PLA Army Medical University — Chongqing, Chongqing, China (Not_yet_recruiting)
• Sun Yat-Sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)
• Henan Cancer Hospital — Zhengzhou, Henan, China (Recruiting)
• Wuhan Union Hospital — Wuhan, Hubei, China (Recruiting)
• The first Affiliated Hospital of China medical University — Shenyang, Liaoning, China (Not_yet_recruiting)
• Ruijin Hospital, Shanghai Jiaotong University School of Medicine — Shanghai, Shanghai, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Hongwei Li, MA.Sc

Conditions Diffuse Large B-cell Lymphoma; Indolent Non-Hodgkin Lymphoma