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Trial record 40 of 182 for:    Venetoclax

Study of Venetoclax (ABT-199) Added to Ibrutinib in Patients With High-Risk Chronic Lymphocytic Leukemia (CLL)

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ClinicalTrials.gov Identifier: NCT03128879
Recruitment Status : Recruiting
First Posted : April 25, 2017
Last Update Posted : September 13, 2018
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if giving the drug venetoclax with ibrutinib can help to control the disease in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The safety of this combination treatment will also be studied.

This is an investigational study. Ibrutinib is FDA approved and commercially available for the treatment of CLL/SLL. Venetoclax is FDA approved for some patients with CLL whose disease has come back after 1 or more previous treatments. The use of venetoclax in combination with ibrutinib is considered investigational.

The study doctor can describe how the study drugs are designed to work.

Up to 45 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Primary Lymphoid Haematopoietic Neoplasms Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Drug: Venetoclax Drug: Ibrutinib Drug: Allopurinol Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Venetoclax (ABT-199) Added to Ibrutinib in Patients With High-Risk Chronic Lymphocytic Leukemia (CLL)
Actual Study Start Date : June 16, 2017
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2023


Arm Intervention/treatment
Experimental: Venetoclax + Ibrutinib
Participants receive Ibrutinib and Venetoclax by mouth once per day.
Drug: Venetoclax

Participants take Venetoclax by mouth on Day 1 of Cycle 1 and dose-escalate according to the following schedule:

i) Day 1 - Venetoclax 20 mg daily. ii) Day 8 - Venetoclax 50 mg daily. iii) Day 15 - Venetoclax 100 mg daily. iv) Day 22 - Venetoclax 200 mg daily. v) Day 29 - Venetoclax 400 mg daily and continuously thereafter.

Other Names:
  • ABT-199
  • GDC-0199

Drug: Ibrutinib
Participants receive Ibrutinib by mouth up to 420 mg per day.
Other Names:
  • PCI-32765
  • Imbruvica

Drug: Allopurinol
Allopurinol 300 mg/day by mouth beginning at least 72 hours prior to Venetoclax dose.
Other Names:
  • Lopurin
  • Zurinol
  • Zyloprim




Primary Outcome Measures :
  1. Overall Response (OR) [ Time Frame: 48 weeks ]
    OR defined as a complete response (CR) or partial response (PR) or CR with incomplete marrow recovery (CRi) as determined by investigator assessment using IWCLL 2008 response criteria.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have a diagnosis of CLL/CLL and EITHER Have high-risk cytogenetic features or molecular features, defined as: del(17p), del(11q), mutated TP53, complex metaphase karyotype (defined as >/=3 unrelated chromosomal abnormalities, present in at least 2 metaphases on conventional, stimulated cytogenetic analysis) OR Have developed a BTK or PLCG2 mutation, detected by sequencing and have not developed disease progression during ibrutinib therapy as defined by IWCLL criteria (Appendix 1) OR B2M has not normalized after 1y ibrutinib therapy or is elevated at the screening *** Note: some patients treated with ibrutinib 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 within the 3 months prior to starting ibrutinib or at some time during their ibrutinib therapy and analyzed at a CLIA-accredited laboratory.
  2. Patients must have received at least 12 months of ibrutinib therapy and have measurable CLL by at least one of the following: Absolute monoclonal lymphocyte count > 4000/microL; 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
  3. Age 18 years or older.
  4. Eastern Cooperative Oncology Group (ECOG) Performance Status </=2.
  5. Patients must have adequate renal and hepatic function: i) Serum bilirubin </=1.5 x upper limit of normal (ULN) or </=3 x ULN for patients with Gilbert's disease ii) Serum creatinine clearance of >/= 50ml/min (calculated or measured) iv) ALT and AST </=3.0 x ULN, unless clearly due to disease involvement.
  6. Adequate bone marrow function: i) Platelet count of greater than 20,000/µl, with no platelet transfusion in prior 2 weeks ii) ANC >/=500/µl in the absence of growth factor support unless due to compromised bone marrow production from CLL, indicated by >/=80% CLL in marrow. iii) Hemoglobin >/=8mg/dL.
  7. INR <1.5
  8. Adequate cardiac function, as assessed by: - Absence of uncontrolled cardiac arrhythmia. - Echocardiogram demonstrating LVEF >/=35%. - NYHA functional class </=2.
  9. Ability to provide informed consent and adhere to the required follow-up.
  10. 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 use both a highly effective method of birth control (eg, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete abstinence, or sterilized partner) and a barrier method (eg., condoms, vaginal ring, sponge, etc) during the period of therapy and for 30 days after the last dose of study drug. Women of non- childbearing potential are those who are postmenopausal (defined as absence of menses for >/=1 year) or who have had a bilateral tubal ligation or hysterectomy. Men who have partners of childbearing potential must agree to use effective contraception, defined above, during the study and for 30 days following the last dose of study drug.
  11. Patients or their legally authorized representative must provide written informed consent.

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 positive serology for human immunodeficiency virus (HIV).
  8. Active hepatitis B infection (defined as the presence of detectable HBV DNA or HBe antigen). Patients who are HBsAg 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 >20mg prednisone daily or equivalent, within 7 days of starting venetoclax.
  11. Received other investigational therapeutic agent for CLL/SLL within 21 days of starting venetoclax.
  12. Concurrent use of warfarin.
  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.

Information from the National Library of Medicine

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): NCT03128879


Contacts
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Contact: Philip A. Thompson, MBBS 713-792-7430 pathompson2@mdanderson.org

Locations
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United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact       pathompson2@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
AbbVie
Investigators
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Principal Investigator: Philip A. Thompson, MBBS M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03128879     History of Changes
Other Study ID Numbers: 2016-0785
NCI-2018-01182 ( Registry Identifier: NCI CTRP )
First Posted: April 25, 2017    Key Record Dates
Last Update Posted: September 13, 2018
Last Verified: September 2018

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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:
Venetoclax
ABT-199
GDC-0199
Primary lymphoid haematopoietic neoplasms
Chronic lymphocytic leukemia
CLL
Small lymphocytic lymphoma
SLL
High risk
Ibrutinib
PCI-32765
Imbruvica
Allopurinol
Lopurin
Zurinol
Zyloprim

Additional relevant MeSH terms:
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Venetoclax
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Neoplasms by Site
Hematologic Diseases
Allopurinol
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Gout Suppressants
Antirheumatic Agents
Free Radical Scavengers
Antioxidants
Protective Agents
Physiological Effects of Drugs