New targeted drugs combined with R-ICE for treating relapsed diffuse large B-cell lymphoma

Clinical Study of Efficacy and Safety of Novel Targeted Drugs Combined With R-ICE Regimen in the Treatment of Relapsed and Refractory Diffuse Large B-cell Lymphoma

This study is testing new targeted drugs combined with the R-ICE treatment to see if they can help people with relapsed diffuse large B-cell lymphoma feel better and improve their chances of recovery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 76 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: rituximab, Zanubrutinib, Tofacitinib
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05348213 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of novel targeted agents combined with the R-ICE regimen in patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL). Participants are categorized based on genetic typing results, and specific targeted drugs are administered according to their subtype. After three treatment cycles, the effectiveness is assessed using PET-CT scans, and eligible patients may proceed to autologous stem cell transplantation. Those who do not qualify for transplantation will receive maintenance therapy with the targeted drugs for up to 12 months.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 75 with confirmed DLBCL who have experienced disease progression after first-line therapy.

Not a fit: Patients with primary central nervous system lymphoma or HIV-associated lymphoma will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more effective treatment option for patients with relapsed and refractory DLBCL.

How similar studies have performed: While there have been studies exploring targeted therapies in lymphoma, this specific combination approach is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* DLBCL was confirmed by histology according to world Health Organization (WHO) disease classification (excluding primary central lymphoma and HIV-associated lymphoma);
* There are evaluable lesions detected by PET/CT;
* Life expectancy of more than 3 months;
* Prior treatment with sufficient first-line anti-lymphoma therapy, no remission within 90 days of the last administration, or disease progression after sufficient first-line anti-lymphoma therapy, and no current anti-lymphoma therapy (≥2 weeks since the last anti-lymphoma therapy). Patients were allowed to receive hormone drugs or rituximab at least 1 week after enrollment for symptom control reasons;
* 18≤ age ≤75 years old, male and female;
* ECOG 0-2 points;
* No serious organic lesions in the main organs, meeting the requirements of the following laboratory examination indicators (conducted within 7 days before treatment) :

  ① Absolute value of neutrophil count ≥1500/mm3; Platelet count ≥75,000/mm3

  ② Total bilirubin ≤2× upper limit of normal value (ULN)

  ③ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (serum glutamate pyruvate aminotransferase \[SGPT\]) ≤3× upper limit of normal value (ULN)

  ④ the creatinine clearance rate was ≥60ml/min

  ⑤ No cardiac dysfunction
* If the subject is of reproductive age and requires effective contraception, he/she agrees to comply with all contraceptive requirements: 1) there are fertile women have to decide, at the same time take two reliable contraceptive methods (a kind of high efficient contraceptives - tubal ligation, intrauterine contraceptive device, hormone (birth control pills, needle, patch, vaginal ring or implants) or partner vasectomy, another effective birth control method -- men or synthetic rubber condom, diaphragm or cervical cap). 2) Unless hysterectomy, effective contraception is required even if there is a history of infertility;
* Fertile men must always use rubber or synthetic condoms when having sexual contact with fertile women during the use of this product and within 28 days of discontinuation of this product, even if they have successfully vasectomy; The subjects knew the characteristics of the disease, voluntarily joined the study, received treatment and follow-up, and the informed consent was signed by the subjects themselves or their guardians and impartial witnesses.

Exclusion Criteria:

* Pregnant or lactating women (lactating women must agree not to breastfeed while taking pomadomide);
* Known hepatitis B (HBV), hepatitis C (HCV) infection (HBV infection refers to HBV-DNA \> detectable limit); And other acquired, congenital immune deficiency disorders, including but not limited to HIV-infected persons;
* Subjects with a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past 12 months;
* Bone marrow failure, defined as ANC\<1500/mm3 or platelet \<75,000/mm3, unless hematologic changes are thought to be associated with lymphomas infiltrating the bone marrow;
* Clinically significant heart disease, including unstable angina, acute myocardial infarction 6 months before enrollment, congestive heart failure (NYHA) heart function grade III or IV; Or left ventricular ejection fraction \<50%;
* Lymphoma with central nervous system (CNS) involvement;
* Those who are known to be allergic to the test drug ingredients;
* Those who have received grade II or above surgery within three weeks before treatment;
* Patients who have received organ transplants;
* Has been diagnosed with or is being treated for malignancy other than lymphoma, except for:

  ① They have received therapeutic treatment and have not had known active disease malignancy for ≥5 years prior to enrollment;

  ② Basal cell carcinoma of the skin (except melanoma) without signs of disease after adequate treatment;

  ③ Cervical carcinoma in situ without signs of disease after adequate treatment.
* With severe infection;
* Substance abuse, medical, psychological, or social conditions that may interfere with the subjects' participation in the study or evaluation of the study results; The researchers deemed unsuitable for the group.

Where this trial is running

Shanghai, Shanghai Municipality

• Ruijin Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: ZHAO weili

Conditions Diffuse Large B Cell Lymphoma; R-ICE+X