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

NCT05322733 | Unknown Phase 2 DMC

• 1 other identifier: CWCLL-001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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)

Conditions

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• BM undetectable MRD rate after 6 cycles

  Participants who achieve bone marrow (BM) undetectable Minimal Residue Disease (uMRD) after 6 cycles detecting by four-color flow cytometry with a detection level of 10-4.

  at the end of 6 cycles(each cycle is 28 days)

Secondary Outcomes (7)

• BM and PB undetectable MRD ratev after 3, 12, 24 cycles.

  at the end of 3, 12, 24 cycles(each cycle is 28 days)

• Objective Response Rate (ORR)

  at the end of 3, 6 cycles and up to approximately 3 years.(each cycle is 28 days)

• Complete Remission Rate (CRR)

  at the end of 3, 6 cycles and up to approximately 3 years.(each cycle is 28 days)

• Duration of Response (DOR)

  up to approximately 2, 3 years

• Progression Free Survival (PFS)

  up to 3 years

Other Outcomes (1)

• PB and BM Undetectable MRD rate by Next-generation Sequencing (NGS ) after 3, 6, 12 and 24 cycles.

  at the end of 3, 6, 12 and 24 cycles(each cycle is 28 days)

Study Arms (1)

Treatment (oFCG)

EXPERIMENTAL

See Detailed Description.

Drug: Orelabrutinib; Drug: Obinutuzumab; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

Orelabrutinib DRUG

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.

Also known as: ICP-022

Treatment (oFCG)

Obinutuzumab DRUG

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).

Also known as: GA101

Treatment (oFCG)

Fludarabine DRUG

25mg/m2/day administered intravenously on Day 1-3 for every cycle (at most 6 cycles, 28-day cycles).

Also known as: Fludara

Treatment (oFCG)

Cyclophosphamide DRUG

250mg/m2/day administered intravenously on Day 1-3 for every cycle (at most 6 cycles, 28-day cycles).

Treatment (oFCG)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 to 65 years old for both gender.
• Patients have a confirmed diagnosis of CD20-positive chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) and meet criteria to initiate first-line treatment per International Workshop on CLL Working Group (IWCLL) 2018 guidelines
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• At least one measurable disease detected by enhanced computerized tomography (CT) or magnetic resonance imaging (MRI). At least one lymph node with the longest axis \>=1.5cm and one measurable vertical dimension.
• With life expectancy \> 6 months.
• Patients must meet the following laboratory examination criteria during 14 days before entry:
• Serum bilirubin \<1.5 Upper Limit of Normal (ULN), other than gilbert syndrome (defined as unconjugated bilirubin\>80%); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 ULN.
• Absolute neutrophil count (ANC)≥0.75×109/L and Platelets≥50×109/L (patients without exposure to G-CSF or blood transfusion within 7 days and no exposure to )

You may not qualify if:

• Cumulative illness rating scale (CIRS) \> 6.
• Creatinine clearance rate (Ccr) \<70 ml/min calculated by Cockcroft-Gault formula or by 24-hour urine analysis.
• Patients diagnosed as other malignancy except lymphoma, except patients with curative intent and with no known active disease present for ≥ 5 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
• Patients with known central nervous system involvement.
• Patients with progressive multifocal leukoencephalopathy (PML).
• Patients with history of Richter's Syndrome or suspected Richter's Syndrome.
• Uncontrolled autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura, e.g. persistent decreasing hemoglobin or platelet count requiring steroid therapy 4 weeks before initiation of study.
• Prior exposure to systemic therapy for CLL/SLL (except for incomplete treatment regimens fewer than 2 weeks such as antitumor steroid therapy).
• Prior exposure to live vaccines, immunotherapy or other investigational therapeutic agent within 4 weeks prior to enrollment.
• Requiring persistent steroid therapy for other non-antitumor purposes. Systemic steroid drug use within 7 days of first dose of study drug except regional use of steroid drug.
• Uncontrolled or other serious cardiovascular disease, including:
• New York Heart Association (NYHA) class II or higher congestive heart failure, unstable angina, myocardial infarction, or clinically significant arrhythmia requiring medical intervention with a left ventricular ejection fraction (LVEF) \<50% at screening 6 months prior to initial administration of the study drug;
• Primary cardiomyopathy (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, rhythmogenesis right ventricular cardiomyopathy, restricted cardiomyopathy, unshaped cardiomyopathy);
• Clinically significant prolonged QTc interval, or QTc interval \>470 ms in female and \>450 ms in male at screening;
• Uncontrolled hypertension: on the basis of lifestyle improvement, blood pressure still fails to reach the standard after application of 2 or more kinds of reasonable, tolerable and full dose antihypertensive drugs (including diuretics), or 4 or more kinds of antihypertensive drugs until blood pressure can be effectively controlled.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital

Nanjin, Jiangsu, 210029, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

orelabrutinib; obinutuzumab; fludarabine; fludarabine phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Jianyong Li, Phd, MD

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianyong Li, Phd, MD

CONTACT

025-83718836; lijianyonglm@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2022
• First Posted: April 12, 2022
• Study Start: April 15, 2022
• Primary Completion: February 22, 2025
• Study Completion: November 5, 2025
• Last Updated: April 19, 2022

Record last verified: 2022-04

Locations

CN (1)