Using Relmacabtagene Autoleucel for treating high-risk large B-cell lymphoma

Study to Evaluate the Efficacy and Safety of Relmacabtagene Autoleucel (Relma-cel) as First-Line Therapy in Adult Participants With High-Risk Large B-Cell Lymphoma

This study is testing a new treatment called Relmacabtagene Autoleucel to see if it can help people with high-risk large B-cell lymphoma who didn't respond well to their first chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Peking University Cancer Hospital & Institute (Academic / other)
• Drugs / interventions: CAR T, chemotherapy
• Locations: 4 sites (Beijing, Beijing and 3 other locations)
• Trial ID: NCT05590221 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of Relmacabtagene Autoleucel as a first-line therapy for patients with high-risk large B-cell lymphoma who have had an incomplete response to initial chemotherapy. It is a prospective, open-label, multicenter, single-arm trial that includes participants with specific high-risk characteristics, such as double- or triple-hit lymphomas. Patients will receive the treatment after two cycles of chemoimmunotherapy and will be monitored for two years post-infusion to assess outcomes.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with histologically confirmed high-risk large B-cell lymphoma and specific prognostic factors.

Not a fit: Patients with low-risk large B-cell lymphoma or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with high-risk large B-cell lymphoma, potentially improving their survival rates.

How similar studies have performed: Other studies have shown promising results with CAR T-cell therapies in similar patient populations, indicating a potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

1. ≥ 18 years old;
2. Sign on the informed consent;
3. Histologically confirmed large B-cell lymphoma that also meets the definition of high-risk large B-cell lymphoma as a lymphoma International Prognostic Index (IPI) score of 3-5 and/or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement (double/triple-hit lymphoma) (DHL/THL) and must be treated with 2 cycles of CD20 monoclonal antibodies combined with anthracyclines. Presence of positive PET assessable lesions (DS score of 4 or 5) as determined by the Lugano criteria (Cheson et al., 2014)；
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
5. Expected survival greater than 12 weeks；
6. Adequate organ function：

   1. Absolute neutrophil count ≥ 1000/μL；Absolute lymphocyte count ≥ 100/μL； Platelet count ≥ 75,000/μL；Hb ≥ 80g/L；
   2. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (Cockcroft-Gault formula) \> 50 mL/min (serum creatinine clearance due to lymphoma mass compression should be \> 30 mL/min)；
   3. Serum alanine aminotransferase (ALT) ≤ 5 upper limit of normal (ULN) and total bilirubin ≤2ULN（or for subjects with Gilbert's syndrome or lymphoma invading the liver \< 3 ULN）；
   4. Baseline oxygen saturation \> 92% on room air；
   5. Left ventricular ejection fraction (LVEF) ≥50% assessed by echocardiography or radionuclide activity angiography (MUGA) within 1 month of enrollment；
7. Adequate vascular access for leukapheresis procedure;
8. Women of childbearing potential must agree to use highly effective methods of contraception for at least 28 days prior to lymphocyte clearance chemotherapy through 1 year after Relmacabtagene Autoleucel infusion; Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for 1 year after Relmacabtagene Autoleucel infusion.

Exclusion Criteria:

1. Lymphoma involving the central nervous system (CNS)；
2. History of another primary malignancy that has not been in remission for at least 2 years;
3. History of Richter's transformation of chronic lymphocytic leukemia or primary mediastinal B-cell lymphoma；
4. Subjects has HBV, HCV, HIV or syphilis infection at the time of screening;
5. Deep venous thrombosis (DVT)/Pulmonary embolism (PE), or DVT/PE requires anti-coagulation within 3 months prior to signing the ICF;
6. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection;
7. Presence of acute or chronic graft-versus-host disease (GVHD);
8. History of any serious cardiovascular disease or presence of clinically relevant CNS pathology;
9. Pregnant or nursing women;
10. Subjects Received an autologous or allogeneic hematopoietic stem cell transplant；
11. Uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol;
12. Received CAR T-cell or other genetically-modified T-cell therapy previously；
13. Received live vaccination within 6 weeks prior to lymphocyte clearance chemotherapy；
14. History of severe hypersensitivity reactions to any of the drug ingredients used in this study product.

Where this trial is running

Beijing, Beijing and 3 other locations

• Beijing Cancer Hospital — Beijing, Beijing, China (Recruiting)
• Peking University International Hospital — Beijing, Beijing, China (Recruiting)
• Henan Cancer Hospital — Zhengzhou, Henan, China (Not_yet_recruiting)
• Tianjin Medical University Cancer Institute and Hospital — Tianjin, Tianjin, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Yuqin Song, PhD — Peking University Cancer Hospital & Institute
• Study coordinator: Yuqin Song, PhD

Conditions B-cell Lymphoma