Venetoclax as Consolidation in CLL Patients Treated With... | NCT06958705

NCT06958705

Status Module

Name	Class
AbbVie	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
CLL/SLL patients on ibrutinib monotherapy for ≥ 6 months	Experimental	Drug: Venetoclax combined with Ibrutinib
CLL/SLL patients on zanubrutinib monotherapy for ≥ 6 months	Experimental	Drug: Venetoclax combined with Zanubrutinib
CLL/SLL patients on acalabrutinib monotherapy for ≥ 6 months	Experimental	Drug: Venetoclax combined with Acalabrutinib
CLL/SLL patients on orelabrutinib monotherapy for ≥ 6 months	Experimental	Drug: Venetoclax combined with Orelabrutinib

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Venetoclax combined with Ibrutinib	Drug	All Patients will be treated with venetoclax for 12 cycles after a standard 5-week dose ramp-up, as an add-on to the primary using ibrutinib. After the completion of combination therapy, patients will stop both the ibrutinib and venetoclax then be followed. Each cycle is 28 days. At the start of cycle 0, patients will start venetoclax by 20mg-50mg-100mg-200mg daily in a weekly dose escalation way. The combination of full dose venetoclax (400mg) and ibrutinib will continue for an additional 12 cycles. Venetoclax and ibrutinib will be continued until the completion of cycle 12, start of new CLL-directed therapies, disease progression or unacceptable toxicities, depending on which comes first. Ibrutinib is intended to be admistratered orally 420mg once daily.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Rate of BM-uMRD after completion of combination therapy (Day 1 of Cycle 16)	Rate of BM-uMRD is defined by negative MRD in the bone marrow by flow cytometry at a sensitivity of 10^-4. The Clopper Pearson method is used to estimate the 95% two-sided confidence interval (CI) of the rate of BM-uMRD.	On Day 1 of Cycle 16 (each cycle is 28 days)

Secondary Outcomes

Measure	Description	Time Frame
Rate of undetected peripheral blood MRD by flow cytometry	Rate of undetected peripheral blood MRD is defined by negative MRD in the peripheral blood by flow cytometry at a sensitivity of 10^-4.	On screening, Day 1 of Cycle 4, Day 1 of Cycle 7, Day 1 of Cycle 10, Day 1 of Cycle 16, Day 1 of Cycle 20, Day 1 of Cycle 24, Day 1 of Cycle 28 and Day 1 of Cycle 34 (each cycle is 28 days)

Other Outcomes

Measure	Description	Time Frame
MRD relapse	MRD relapse is now defined as either: (1) conversion of MRD negativity to MRD positivity, independent of the MRD technique, or (2) increase of MRD ≥ 1 log10 between any 2 positive samples measured in the same tissue (PB or BM) in patients with MRD+ CLL.	From the date of MRD negativity to the date of MRD positivity or the occurrence of increase of MRD ≥ 1 log10 between any 2 positive samples measured in the same tissue, assessed up to 112 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

1. Age: 18-80 years-old.
2. Patients must have a diagnosis of CLL/SLL.
3. Detectable MRD by flow cytometry (10^-4 sensitivity) in the peripheral blood.
4. Patients who are on BTK inhibitor monotherapy for more than 6 months. This study includes patients who are taking one of the following BTK inhibitors: ibrutinib, zanubrutinib, orelabrutinib, and acalabrutinib.
5. Patients need to have a response of at least PR (CR/PR) to BTK inhibitor monotherapy.
6. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
7. Patients must have adequate renal and hepatic function:
Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for patients with Gilbert's disease;
Serum creatinine clearance of ≥ 50 ml/min (calculated or measured);
ALT and AST ≤ 3.0 × ULN, unless clearly due to disease involvement.
8. Adequate bone marrow function:
Platelet count of greater than 50,000/µl, with no platelet transfusion in prior 2 weeks;
ANC ≥ 1000/µl in the absence of growth factor support unless due to compromised bone marrow production from CLL, indicated by ≥ 80% CLL in marrow;
Hemoglobin ≥ 8g/dL.
9. Adequate cardiac function, as assessed by:
Absence of uncontrolled cardiac arrhythmia;
Echocardiogram demonstrating LVEF ≥ 35%;
NYHA functional class ≤ 2.
10. Ability to provide informed consent and adhere to the required follow-up.

Exclusion Criteria:

1. Richter transformation.
2. Active malignancy requiring systemic therapy, other than CLL, with the exception of: adequately treated in situ carcinoma of the cervix uteri; adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
3. Major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 3 weeks prior to the first dose of the study drug.
4. Grade 3 or 4 hemorrhage within the past 3 weeks.
5. Uncontrolled active infections (viral, bacterial, and fungal).
6. Females who are pregnant or lactating.
7. Known HIV positive.
8. Active hepatitis B infection (defined as the presence of detectable HBV DNA or HBe antigen). Patients who are HBsAg positive or HBcAb positive are eligible, provided HBV DNA is negative. These patients must have monthly monitoring of HBV DNA for the duration of the study.
9. Active hepatitis C, defined by the detection of hepatitis C RNA in plasma by PCR.
10. Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy > 20 mg prednisone daily or equivalent, within 7 days of starting venetoclax.
11. Received other therapeutic agents for CLL/SLL during BTK inhibitor treatment prior to enrollment.
12. Concurrent use of warfarin or equivalent vitamin K inhibitor or other oral anticoagulant treatment.
13. Received strong CYP3A inhibitors or strong CYP3A inducers within 7 days of starting venetoclax.
14. Consuming grapefruit, grapefruit products, Seville oranges, or star fruit within 7 days of starting venetoclax.
15. Prior treatment with venetoclax or other Bcl-2 inhibitor.
16. Malabsorption syndrome or other condition that precludes enteral route of administration.

Name	Role	Phone	Extension	Email
Jianyong Li, PhD, MD	Contact	86-13951877733		lijianyonglm@126.com
Huayuan Zhu, PhD, MD	Contact	86-13813810650		huayuan.zhu@hotmail.com

ID	Term
D015448	Leukemia, B-Cell
D007945	Leukemia, Lymphoid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C551803	ibrutinib
C000629551	zanubrutinib
C000604908	acalabrutinib
C000729508	orelabrutinib