Venetoclax With Ibrutinib or Acalabrutinib in Pts. With High-risk CLL

NCT03128879 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2016-0785NCI-2018-01182
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, open-label, phase II study of venetoclax (ABT-199) added to ibrutinib or acalabrutinib in patients with high-risk CLL who have received at least 12 months of ibrutinib or acalabrutinib monotherapy. The study will estimate the therapeutic efficacy of venetoclax consolidation in patients who have detectable CLL after receiving ibrutinib or acalabrutinib for at least 12 months and who have high risk CLL.

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• The primary endpoint will be the rate of MRD-negativity in the bone marrow, using an assay method with at least 0.01% sensitivity after 12 cycles of combination therapy. One cycle is 4 weeks of treatment.

  One cycle is 4 weeks of treatment. (each cycle 28 days)

  through study completion, an average of 1 year

Secondary Outcomes (5)

• Determine complete remission CR/complete remission with incomplete hematologic recovery CRi rate of combination therapy in patients who were not in CR/Cri at study initiation and estimate the time to best response with this combination.

  through study completion, an average of 1 year

• Determine the cumulative rate of bone marrow minimal residual disease (MRD)-free complete responders by an assay method with at least 0.01% sensitivity and median time to MRD-negativity.

  through study completion, an average of 1 year

• Determine the safety of combined ibrutinib and venetoclax.

  through study completion, an average of 1 year

• Determine the progression-free survival

  through study completion, an average of 1 year

• Determine the overall survival.

  through study completion, an average of 1 year

Study Arms (1)

Treatment (venetoclax, ibrutinib, acalabarutinib)

EXPERIMENTAL

Patients receive venetoclax PO QD and ibrutinib PO QD and acalabrutinib PO BID. Treatment repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unaccepted toxicity.

Drug: Ibrutinib; Drug: Venetoclax; Drug: Acalabrutinib

Interventions

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (venetoclax, ibrutinib, acalabarutinib)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (venetoclax, ibrutinib, acalabarutinib)

Acalabrutinib DRUG

Given BID

Treatment (venetoclax, ibrutinib, acalabarutinib)

Eligibility Criteria

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

You may qualify if:

• Patients must have a diagnosis of CLL/CLL and have high-risk cytogenetic features or molecular features, defined as: del(17p), mutated TP53, complex metaphase karyotype (defined as 3 unrelated chromosomal abnormalities, present in at least 2 metaphases on conventional, stimulated cytogenetic analysis)
• \*\*\* Note: some patients treated with ibrutinib or acalabrutinib may no longer have detectable FISH, karyotypic or molecular abnormalities after 12 months of therapy. These patients will be eligible if they fulfill the above criteria on a bone marrow biopsy or peripheral blood specimen taken either prior to starting ibrutinib or acalabrutinib, provided they did not receive treatment for their CLL between the date of the lab test and starting ibrutinib or acalabrutinib or at some time during their ibrutinib therapy and analyzed at a CLIA-accredited laboratory.
• Patients must have received at least 12 months of ibrutinib or acalabrutinib therapy and have measurable CLL by at least one of the following:
• Absolute monoclonal lymphocyte count \> 4000/L; OR
• Measurable lymph nodes with at least one node \>1.5 cm in diameter on CT; OR
• Bone marrow with \>/= 30% lymphocytes on aspirate differential OR
• Detectable CLL cells using a standardized flow cytometry assay for minimal residual disease
• Age 18 years or older.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
• Patients must have adequate renal and hepatic function:
• Serum bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for patients with Gilbert's disease.
• Serum creatinine clearance of 50ml/min (calculated or measured).
• ALT and AST ≤3.0 x ULN, unless clearly due to disease involvement.
• Adequate bone marrow function:
• Platelet count of greater than 50,000/µl, with no platelet transfusion in prior 2 weeks.

You may not qualify if:

• Richter transformation.
• 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.
• Major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 3 weeks prior to the first dose of the study drug.
• Grade 3 or 4 hemorrhage within the past 3 weeks.
• Uncontrolled active infections (viral, bacterial, and fungal).
• Females who are pregnant or lactating.
• Known positive serology for human immunodeficiency virus (HIV).
• 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 will have monthly monitoring of HBV DNA for the duration of the study, if clinically indicated. Please note that patients who have received IVIG may have false positive HBcAb results. In such patients, if HBV DNA and HBsAg are negative, serial HBV DNA monitoring is not necessary.
• Active hepatitis C, defined by the detection of hepatitis C RNA in plasma by PCR.
• Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy \>20mg prednisone daily or equivalent, within 7 days of starting venetoclax.
• Received other investigational therapeutic agent for CLL/SLL within 21 days of starting venetoclax.
• Concurrent use of warfarin.
• Received strong CYP3A inhibitors or strong CYP3A inducers within 7 days of starting venetoclax.
• Consuming grapefruit, grapefruit products, Seville oranges, or star fruit within 7 days of starting venetoclax.
• Prior treatment with venetoclax or other Bcl-2 inhibitor.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ibrutinib; venetoclax; acalabrutinib

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

Study Officials

• Alessandra Ferrajoli, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alessandra Ferrajoli, MD

CONTACT

(713) 792-2063; aferrajo@mdanderson.org

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: April 21, 2017
• First Posted: April 25, 2017
• Study Start: June 16, 2017
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: November 21, 2025

Record last verified: 2025-11

Locations

US (1)