Venetoclax and Ibrutinib in Patients With Chronic Lymphocytic Leukemia (CLL)
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ClinicalTrials.gov Identifier: NCT02756897 |
Recruitment Status
:
Recruiting
First Posted
: April 29, 2016
Last Update Posted
: April 18, 2018
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The goal of this clinical research study is to learn if venetoclax given in combination with ibrutinib can help to control CLL or SLL. The safety of the drug combination will be also studied.
This is an investigational study. Ibrutinib is FDA approved and commercially available for the treatment of patients with mantle cell lymphoma and in patients with CLL who have received at least 1 prior treatment. Its use in this study is investigational. Venetoclax is FDA approved and commercially available for the treatment of patients with CLL who have have received at least 1 prior treatment. The combination of venetoclax and ibrutinib is investigational.
The study doctor can describe how the study drugs are designed to work.
Up to 160 participants will be enrolled in this study. All will take part at MD Anderson.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Leukemia Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma | Drug: Ibrutinib Drug: Venetoclax | Phase 2 |

Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 160 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase II Study of Venetoclax and Ibrutinib in Patients With Chronic Lymphocytic Leukemia (CLL) |
Actual Study Start Date : | July 7, 2016 |
Estimated Primary Completion Date : | July 2024 |
Estimated Study Completion Date : | July 2025 |

Arm | Intervention/treatment |
---|---|
Experimental: Relapsed/Refractory CLL Group
Participants receive Ibrutinib monotherapy for 3 cycles. Each cycle is 4 weeks. At the start of cycle 4, Venetoclax added as a weekly dose escalation. The combination of Venetoclax and Ibrutinib continues for an additional 24 cycles for a total of 27 cycles of treatment.
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Drug: Ibrutinib
420 mg by mouth once daily in a 28 day cycle.
Other Names:
Drug: Venetoclax
At the start of cycle 4 Venetoclax taken by mouth as weekly dose escalation: 20 mg daily for 1 week, 50 mg daily for 1 week, 100 mg daily for 1 week, 200 mg daily for 1 week, then 400 mg daily for duration of treatment. Other Names:
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Experimental: High-Risk CLL Participants With No Prior Therapy Group
Participants receive Ibrutinib monotherapy for 3 cycles. Each cycle is 4 weeks. At the start of cycle 4, Venetoclax added as a weekly dose escalation. The combination of Venetoclax and Ibrutinib continues for an additional 24 cycles for a total of 27 cycles of treatment.
|
Drug: Ibrutinib
420 mg by mouth once daily in a 28 day cycle.
Other Names:
Drug: Venetoclax
At the start of cycle 4 Venetoclax taken by mouth as weekly dose escalation: 20 mg daily for 1 week, 50 mg daily for 1 week, 100 mg daily for 1 week, 200 mg daily for 1 week, then 400 mg daily for duration of treatment. Other Names:
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- Best Response (CR/CRi)) of Combined Ibrutinib and Venetoclax in Participants with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) [ Time Frame: Start of drug combination up to 2 months after drug combination stopped ]Response defined as a complete response (CR) or partial response (PR) (or CR with incomplete marrow recovery) as determined by investigator assessment using CLL response criteria.

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Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients with a diagnosis of CLL/SLL who are refractory to and/or relapsed after at least one prior therapy will be eligible (Cohort 1). Untreated patients with high-risk features (del(17p), or mutated TP53, or del(11q), or unmutated IGHV, or >/= 65 years of age) are eligible (Cohort 2) provided they have active disease requiring treatment as defined by the International Working Group for CLL (IWCLL)
- Age 18 years or older
- Eastern Cooperative Oncology Group (ECOG) Performance Status </=2
- Patients must have 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 (In pts with elevated total bilirubin due to increased indirect bilirubin, pts with direct bilirubin </= 1.5 x ULN are eligible), -- Creatinine clearance >50 mL/min (calculated according to institutional standards or using Cockcroft-Gault , MDRD, or CKD-EPI formula), -- alanine aminotransferase (ALT) and alanine aminotransferase (AST) </=3.0 x ULN, unless clearly due to disease involvement
- Platelet count of greater than 20,000/mul, with no platelet transfusion in 2 weeks prior to registration. This criteria is waived if the thrombocytopenia is due to bone marrow involvement with the disease
- Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (Beta-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 30 days following the last dose of study drug. 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 have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug
- 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.
- Patients or their legally authorized representative must provide written informed consent
Exclusion Criteria:
- Major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, investigational therapy within 3 weeks prior to the first dose of the study drugs
- Uncontrolled active systemic infection (viral, bacterial, and fungal)
- Known positive serology for human immunodeficiency virus (HIV), due to potential drug-drug interactions between anti-retroviral medications and the study drugs
- 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. NOTE - definitions for abbreviations: HBV - hepatitis B virus; DNA - deoxyribonucleic acid; HBe - hepatitis B e; anti-HBs - hepatitis B surface antibody; anti-HBc - hepatitis B core antibody; HBsAg - hepatitis B surface antigen; HBsAb - hepatitis B surface antibody; HBcAb - hepatitis B core antibody
- Active hepatitis C, defined by the detectable hepatitis C ribonucleic acid (RNA) in plasma by polymerase chain reaction (PCR)
- Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy with >20mg daily of prednisone dose or equivalent
- Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 2 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.
- Patient is pregnant or breast-feeding
- Concurrent use of warfarin
- Received strong (CYP3A) inhibitors or strong CYP3A inducers within 7 days of starting study drugs
- Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 7 days of starting study drugs
- Prior treatment with venetoclax or ibrutinib
- Malabsorption syndrome or other condition that precludes enteral route of administration
- 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02756897
Contact: Nitin Jain, MBBS | 713-745-6080 |
United States, Texas | |
University of Texas MD Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 |
Principal Investigator: | Nitin Jain, MBBS | M.D. Anderson Cancer Center |
Additional Information:
Responsible Party: | M.D. Anderson Cancer Center |
ClinicalTrials.gov Identifier: | NCT02756897 History of Changes |
Other Study ID Numbers: |
2015-0860 NCI-2016-00797 ( Registry Identifier: NCI CTRP ) |
First Posted: | April 29, 2016 Key Record Dates |
Last Update Posted: | April 18, 2018 |
Last Verified: | April 2018 |
Studies a U.S. FDA-regulated Drug Product: | Yes | |
Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by M.D. Anderson Cancer Center:
Leukemia Chronic Lymphocytic Leukemia CLL Small Lymphocytic Lymphoma SLL Refractory and/or relapsed |
Ibrutinib PCI-32765 Imbruvica Venetoclax ABT-199 GDC-0199 |
Additional relevant MeSH terms:
Leukemia Leukemia, Lymphoid Leukemia, Lymphocytic, Chronic, B-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders |
Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Leukemia, B-Cell Venetoclax Antineoplastic Agents |