RECRUITING

Acalabrutinib and Venetoclax with or Without Early Obinutuzumab for the Treatment of High Risk, Recurrent, or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Conditions

Recurrent Chronic Lymphocytic Leukemia Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Small Lymphocytic Lymphoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase II trial studies how well acalabrutinib and venetoclax with or without early obinutuzumab work for the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma that is high risk, has come back (recurrent), or does not respond to treatment (refractory). Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Venetoclax may stop the growth cancer cells by blocking BCL-2 protein needed for cell growth. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving acalabrutinib and venetoclax together with early obinutuzumab may improve clinical outcomes and control the disease.

Official Title

A Randomized Phase II Study of Acalabrutinib (ACA) + Venetoclax (VEN) +/- Early Obinutuzumab (OBIN) for Patients with Chronic Lymphocytic Leukemia (CLL)

Quick Facts

Study Start:2020-07-29

Study Completion:2026-07-09

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04169737

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Patients with a diagnosis of CLL/SLL and indication for treatment by 2018 iwCLL criteria: 2. Age 18 years or older 3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2 4. Adequate renal and hepatic function: * Total bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for patients with Gilbert's disease * Creatinine clearance \>50 mL/min (calculated according to institutional standards or using Cockcroft-Gault, MDRD, or CKD-EPI formula) * ALT and AST ≤3.0 x ULN, unless clearly due to disease involvement 5. Absolute neutrophil count greater than 750 neutrophils/L, unless thought to be due to marrow infiltration with CLL. Platelet count of greater than 30,000/µl, with no platelet transfusion in 2 weeks prior to registration , unless thought to be due to marrow infiltration with CLL. 6. Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test result within 7 days prior to the first dose of study drugs and must agree to use an effective contraception method during the study and for 2 days after the last dose of acalabrutinib, 30 days after the last dose of venetoclax, or 18 months after the last dose of obinutuzumab, whichever is longer. Women of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. Men who are sexually active must agree to use highly effective forms of contraception with the addition of a barrier method (condom) during the study and for 30 days after the last dose of venetoclax and for 18 months after the last dose obinutuzumab, whichever is longer. 7. Free of prior malignancies for 2 years with exception of patients diagnosed with basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast, who are eligible even if they are currently treated or have been treated and/or diagnosed in the past 2 years prior to study enrolment. If patients have another malignancy that was treated within the last 2 years, such patients may be enrolled, if the likelihood of requiring systemic therapy for this other malignancy within 2 years is less than 10%, as determined by an expert in that particular malignancy at MD Anderson Cancer Center, and after consultation with the Principal Investigator. 8. Patients must provide written informed consent.	1. Prior treatment with combined BTKi and BCL2i where patients do not achieve at least partial response or progress and need new treatment within 2 years of completing fixed-duration combined treatment. 2. Major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, investigational therapy or live virus vaccination within 3 weeks prior to the first dose of the study drugs, unless patients have rapidly progressive disease, in which case, washout will be 3 drug half-lives 3. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products 4. Uncontrolled clinically significant active infection (viral, bacterial, and fungal) 5. Known positive serology for human immunodeficiency virus (HIV), due to potential drug-drug interactions between anti-retroviral medications and the study drugs 6. Active hepatitis B infection (defined as the presence of detectable HBV DNA, HBe antigen or HBs antigen). Subjects with serologic evidence of prior vaccination (HBsAg negative, anti-HBs antibody positive, anti-HBc antibody negative) are eligible. Patients who are HBsAg negative/HBsAb positive but HBcAb positive are eligible, provided HBV DNA is negative. 7. Active hepatitis C, defined by the detectable hepatitis C RNA in plasma by PCR 8. Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy with \>20mg daily of prednisone dose or equivalent 9. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. 10. Patient is pregnant or breast-feeding 11. Concurrent use of warfarin 12. Received strong CYP3A inhibitors or strong CYP3A inducers within 7 days of starting study drugs and throughout venetoclax administration 13. Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 7 days of starting venetoclax 14. Known bleeding disorder or history of stroke or intracranial hemorrhage within past 6 months 15. Malabsorption syndrome or other condition that precludes enteral route of administration 16. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study.

Inclusion Criteria

Exclusion Criteria

1. Patients with a diagnosis of CLL/SLL and indication for treatment by 2018 iwCLL criteria:
2. Age 18 years or older
3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2
4. Adequate renal and hepatic function:
* Total bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for patients with Gilbert's disease
* Creatinine clearance \>50 mL/min (calculated according to institutional standards or using Cockcroft-Gault, MDRD, or CKD-EPI formula)
* ALT and AST ≤3.0 x ULN, unless clearly due to disease involvement
5. Absolute neutrophil count greater than 750 neutrophils/L, unless thought to be due to marrow infiltration with CLL. Platelet count of greater than 30,000/µl, with no platelet transfusion in 2 weeks prior to registration , unless thought to be due to marrow infiltration with CLL.
6. Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test result within 7 days prior to the first dose of study drugs and must agree to use an effective contraception method during the study and for 2 days after the last dose of acalabrutinib, 30 days after the last dose of venetoclax, or 18 months after the last dose of obinutuzumab, whichever is longer. Women of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. Men who are sexually active must agree to use highly effective forms of contraception with the addition of a barrier method (condom) during the study and for 30 days after the last dose of venetoclax and for 18 months after the last dose obinutuzumab, whichever is longer.
7. Free of prior malignancies for 2 years with exception of patients diagnosed with basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast, who are eligible even if they are currently treated or have been treated and/or diagnosed in the past 2 years prior to study enrolment. If patients have another malignancy that was treated within the last 2 years, such patients may be enrolled, if the likelihood of requiring systemic therapy for this other malignancy within 2 years is less than 10%, as determined by an expert in that particular malignancy at MD Anderson Cancer Center, and after consultation with the Principal Investigator.
8. Patients must provide written informed consent.

1. Prior treatment with combined BTKi and BCL2i where patients do not achieve at least partial response or progress and need new treatment within 2 years of completing fixed-duration combined treatment.
2. Major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, investigational therapy or live virus vaccination within 3 weeks prior to the first dose of the study drugs, unless patients have rapidly progressive disease, in which case, washout will be 3 drug half-lives
3. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
4. Uncontrolled clinically significant active infection (viral, bacterial, and fungal)
5. Known positive serology for human immunodeficiency virus (HIV), due to potential drug-drug interactions between anti-retroviral medications and the study drugs
6. Active hepatitis B infection (defined as the presence of detectable HBV DNA, HBe antigen or HBs antigen). Subjects with serologic evidence of prior vaccination (HBsAg negative, anti-HBs antibody positive, anti-HBc antibody negative) are eligible. Patients who are HBsAg negative/HBsAb positive but HBcAb positive are eligible, provided HBV DNA is negative.
7. Active hepatitis C, defined by the detectable hepatitis C RNA in plasma by PCR
8. Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy with \>20mg daily of prednisone dose or equivalent
9. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.
10. Patient is pregnant or breast-feeding
11. Concurrent use of warfarin
12. Received strong CYP3A inhibitors or strong CYP3A inducers within 7 days of starting study drugs and throughout venetoclax administration
13. Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 7 days of starting venetoclax
14. Known bleeding disorder or history of stroke or intracranial hemorrhage within past 6 months
15. Malabsorption syndrome or other condition that precludes enteral route of administration
16. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study.

Contacts and Locations

Study Contact

William G Wierda

CONTACT

713-745-0428

wwierda@mdanderson.org

Principal Investigator

William G Wierda

PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Study Locations (Sites)

M D Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

William G Wierda, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-07-29

Study Completion Date2026-07-09

Study Record Updates

Study Start Date2020-07-29

Study Completion Date2026-07-09

Terms related to this study

Additional Relevant MeSH Terms

Recurrent Chronic Lymphocytic Leukemia
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Small Lymphocytic Lymphoma