NCT05322733

Orelabrutinib and Obinutuzumab Plus FC Regimen in Treating Newly Diagnosed CLL/SLL

Efficacy and Safety of Orelabrutinib, Fludarabine, Cyclophosphamide, and Obinutuzumab (GA-101) (oFCG) in the Treatment of Newly Diagnosed Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: The First Affiliated Hospital with Nanjing Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This study is a multi-center, open-label, single-arm, non-randomized phase II clinical study in order to evaluate the safety and efficacy of Orelabrutinib, Fludarabine, Cyclophosphamide, and Obinutuzumab (GA-101) (oFCG) in the Treatment of Newly Diagnosed Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)

Detailed description

Patients eligible for enrollment will receive 7-day lead-in therapy of orelabrutinib 150 mg once daily, followed by 3 cycles of orelabrutinib, fludarabine, cyclophosphamide, and obinutuzumab (oFCG) at 28-day intervals. After 3 cycles, bone marrow (BM) minimal residual disease (MRD) detection and efficacy evaluation (iwCLL2018 guidelines) are conducted. If BM MRD is negative (\<10-4), patients will receive be treated with orelabrutinib plus obinutuzumab in 4-6 cycles; If BM MRD is positive (≥10-4), patients will receive the same regimen in 4-6 cycles as in previous 3 cycles. After 6 cycles of treatment, BM MRD detection and efficacy assessment will be conducted again. If BM MRD is negative (\<10-4), orelabrutinib monotherapy will be administered in 7-12 cycles; If BM MRD is positive (≥10-4), treatment with orelabrutinib plus obinutuzumab will be administered in 7-12 cycles. After 12 cycles of treatment, BM MRD detection and efficacy evaluation will be performed. If BM MRD is negative (\<10-4), orelabrutinib will be withdrawn and participants will turn to follow-up (efficacy assessment and MRD test will be performed according to the follow-up plan); if BM MRD is positive, treatment with orelabrutinib monotherapy will be administered in 13-24 cycles (continued even if BM MRD test was negative). After 24 cycles, if BM MRD is negative, the drug can be stopped and participants turn to follow-up. If BM MRD is positive, treatment can be continued until disease progression or be ceased by investigator due to no benefit from continued treatment, and BM MRD can be tested as planned. The trial is expected to end 36 months after enrollment of the last patient. If the subjects continue to require subsequent treatment with orelabrutinib, the sponsor will coordinate with the manufacturer and continue to provide the monotherapy treatment.

Conditions

• Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Interventions

Type	Name	Description
DRUG	Orelabrutinib	150 mg capsules administered orally once daily (28-day cycles). Until 12 or 24 cycles and following BM undetectable MRD, or disease progression, or intolerant toxicity.
DRUG	Obinutuzumab	1000 mg administered intravenously once on Day 1, 8, 15 of first cycle and on Day 1 of following cycles for maximal 12 cycles (28-day cycles).
DRUG	Fludarabine	25mg/m2/day administered intravenously on Day 1-3 for every cycle (at most 6 cycles, 28-day cycles).
DRUG	Cyclophosphamide	250mg/m2/day administered intravenously on Day 1-3 for every cycle (at most 6 cycles, 28-day cycles).

Timeline

• Start date: 2022-04-15
• Primary completion: 2025-02-22
• Completion: 2025-11-05
• First posted: 2022-04-12
• Last updated: 2022-04-19

Locations

1 site across 1 country: China