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Clinical Trials List

Protocol NumberM14-728
NCT Number(ClinicalTrials.gov Identfier)NCT02966756
Active

2018-06-26 - 2030-12-31

Phase II

Recruiting7

ICD-10C91.10

Chronic lymphocytic leukemia of B-cell type not having achieved remission

A Phase 2 Open-Label Study of the Efficacy of Venetoclax in Subjects with Relapsed or Refractory Chronic Lymphocytic Leukemia in the Presence of 17p Deletion

  • Trial Applicant

    AbbVie

  • Sponsor

    AbbVie

  • Trial scale

    Multi-Regional Multi-Center

  • Update

    2026/02/01

Investigators and Locations

Principal Investigator Su-Peng Yeh Division of Hematology & Oncology
China Medical University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator 林炫聿 Division of Hematology & Oncology
CHANGHUA CHRISTIAN HOSPITAL

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Su-Peng Yeh 未分科
China Medical University Hospital-Taipei

Co-Principal Investigator

Audit

None

Principal Investigator Ming-Chung Kao Division of Hematology & Oncology
Linkou Chang Gung Medical Foundation

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Audit

None

Principal Investigator Shang-Ju Wu Division of Hematology & Oncology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Audit

None

Principal Investigator Yi-Chang Liu Division of Hematology & Oncology
Kaohsiung Medical Univeristy Chung-Ho Memorial Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Shang-Ju Wu Division of Hematology & Oncology
National Taiwan University Hospital Hsin-Chu Branch

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Yi-Chang Liu Division of Hematology & Oncology
Kaohsiung Municipal Ta-Tung Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Condition/Disease

Chronic Lymphocytic Leukemia

Objectives

Primary objective: The primary objective is to evaluate the overall response rate (ORR) of venetoclax (ABT-199/GDC-0199) monotherapy in subjects with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) in the presence of 17p deletion. Secondary objectives: The secondary objectives are to evaluate the complete remission (CR) rate, partial remission (PR) rate, progression free survival (PFS), event free survival (EFS), time to progression (TTP), time to 50% reduction in absolute lymphocyte count (ALC), overall survival (OS) and percent of subjects who move on to stem cell transplant. The safety and tolerability of venetoclax in subjects with relapsed or refractory CLL in the presence of 17p deletion will also be evaluated. Exploratory objectives: Minimal residual disease (MRD) assessed in both peripheral blood and the bone marrow, time to next anti-CLL treatment (TTNT), and pharmacokinetics may be evaluated as exploratory objectives. Time to first response and duration of overall response (DOR) will be assessed in a subset of subjects who elect to have optional CT scans performed at Weeks 5, 12, and 24. Health Economic and Patient Reported Outcome Measure will be the EORTC QLQ-C30.

Test Drug

Venetoclax

Active Ingredient

Venetoclax

Dosage Form

tablet

Dosage

20mg

Endpoints

1. Efficacy: Response will be assessed by the investigator, based on laboratory values, CT scans (or MRI if CT scan is medically contraindicated), and bone marrow examinations, using the 2008 Modified IWCLL NCI-WG Guidelines for Tumor Response.
In addition to being reviewed by the investigator, an Independent Review Committee (IRC) will also assess tumor response and disease progression. Clinical data and radiographic scans will be interpreted according to 2008 Modified IWCLL NCI-WG Guidelines for Tumor Response. The independent review facility will provide instructions regarding the preparation and shipment of the data. Interpretations from the independent review will not be sent to the site. Subject treatment management will be based on review by the local investigator.
All measurable disease must be documented at Screening by physical examination, laboratory testing, CT scan (or MRI if CT is medically contraindicated), and bone marrow. Subjects will undergo response assessment at baseline and at Week 36. Optional CT scans may be obtained at Weeks 5, 12, and 24. All subjects will undergo a bone marrow biopsy and aspirate at Week 36.
Subjects who no longer have measurable disease must have a negative bone marrow biopsy and aspirate to document complete remission (CR) status. Subjects with CR will not require response assessment after Week 36. Subjects with partial remission (PR) or stable disease (SD) will continue response assessments at Week 48 and then every 24 weeks thereafter until achieving CR, disease progression, death, discontinuation from the study, or study completion.
2. Safety: Adverse event monitoring, vital signs, physical examination, ECG, electrocardiogram or a Multi Gated Acquisition Scan and laboratory assessments will be summarized. Guidelines for the prophylaxis, monitoring and management of TLS are provided.
3. Pharmacokinetics: Pharmacokinetic samples will be collected for venetoclax at designated time points throughout the study. The first 12 subjects enrolled from China mainland must undergo intensive PK sampling. For these 12 subjects, values for PK parameters of venetoclax (and possible metabolites), including the maximum observed plasma concentration (Cmax), the time to Cmax(peak time, Tmax), the terminal phase elimination rate constant (β), terminal elimination half-life (t1/2), the area under the plasma concentration-time curve (AUC) from time 0 to last measurable concentration (AUCt), from time 0 to infinite time (AUC∞), and over a 24-hour dose interval (AUC0-24) will be determined as applicable, using non-compartmental methods. Values for the PK parameters of venetoclax, including the apparent clearance (CL/F) and the apparent volume of distribution (V/F), may be determined using a population PK approach. Additional parameters may be calculated if useful in the interpretation of the data.
4. Quality of life: Quality of life will be evaluate by using questionnaire EORTC QLQ-C30 at specific time points throughout the study.

Inclution Criteria

1. Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures.
2. Subject must be ≥ 18 years of age.
3. Subject must have a diagnosis of relapsed or refractory CLL that meets 2008 Modified IWCLL NCI-WG Guidelines and the following.
 Subject must have an indication for treatment according to the 2008 Modified IWCLL NCIWG Guidelines;
 Subject must have measurable disease (B-lymphocytosis > 5 × 109 /L or an enlarged lymph node(s) (LDi > 1.5 cm at baseline) or hepatomegaly or splenomegaly due to CLL);
 Subject must have relapsed or refractory CLL after receiving at least one prior line of therapy
Relapsed – must have completed at least 2 cycles of one prior line of therapy;
Refractory – must have progressed after at least 1 cycle of one prior line of therapy;
 Subject must have 17p deletion, assessed by a central laboratory (in peripheral blood).
4. Subject must have an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.
5. Subject must have adequate bone marrow function at Screening as follows:
 Absolute Neutrophil Count (ANC) ≥ 1000/μL, or
o for subjects with an ANC < 1000/μL at Screening and bone marrow heavily infiltrated with underlying disease, growth factor support may be administered after Screening and prior to the first dose of venetoclax to achieve the ANC eligibility criteria (≥ 1000/μL);
 Platelets ≥ 30,000/mm3
o without transfusion support within 14 days of Screening,
o without evidence of mucosal bleeding,
o without a history of bleeding episode within 3 months of Screening,
o without a history of a bleeding disorder.
 Hemoglobin ≥ 8.0 g/dL.
6. Subject must have adequate coagulation, hepatic, and renal function, per laboratory reference range at Screening as follows:
 Activated partial thromboplastin time (aPTT) and prothrombin time (PT) must not exceed 1.5 × the upper limit of normal (ULN);
 Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be ≤ 3.0 × ULN; bilirubin ≤ 1.5 × ULN. Subjects with Gilbert's Syndrome may have a bilirubin > 1.5 × ULN, per correspondence between the investigator and the AbbVie medical monitor;
 Calculated creatinine clearance > 50 mL/min using any of the following:
o 24-hour Creatinine Clearance
o modified Cockcroft-Gault equation (using Ideal Body Mass [IBM] instead of Mass):
eCCr = (140 – Age) × IBM (kg) × [0.85 if Female]
72 × Serum Creatinine (mg/dL)
Or, if serum creatinine is in μmol/L:
eCCr = (140 – Age) × IBM (kg) × [1.23 if Male, 1.04 if Female]
Serum Creatinine (μmol/L)
Ideal Body Mass should be used:
IBM (kg) = [(height cm – 154) × 0.9] + (50 if Male, 45.5 if Female)
Note: For subjects who have a BMI of > 30 kg/m2 or < 19 kg/m2 , 24-hour measured urine creatinine clearance is required.
o Chinese Modification of Diet in Renal Disease (C-MDRD) (required eGFR > 50 mL/min/1.73m2 )
 eGFR = 175 × (Serum Creatinine)–1.234 × (Age)–0.179 × (0.79 if female).
7. If female, subject must be either postmenopausal defined as:
 Age > 55 years with no menses for 12 or more months without an alternative medical cause
 Age ≤ 55 years with no menses for 12 or more months without an alternative medical cause AND an FSH level > 40 IU/L
OR
 Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
OR
 Women of Childbearing Potential (WOCBP) practicing at least one protocol specified method of birth control (Section 5.2.4), starting at Study Day 1 through at least 30 days after the last dose of venetoclax.
8. Females of childbearing potential must have a negative serum pregnancy test result at Screening, and a negative urine pregnancy test at Study Day 1. Females of non-bearing potential (either postmenopausal or prematurely surgically sterile as defined above) at Screening do not require pregnancy testing.
9. Male subjects must agree to refrain from sperm donation from initial venetoclax administration until 90 days after the last dose of venetoclax.
10. For high risk subjects approval by the AbbVie medical monitor is required prior to enrollment.

Exclusion Criteria

1. Subject has undergone an allogeneic stem cell transplant.
2. Subject has developed Richter's transformation confirmed by biopsy.
3. Subject has prolymphocytic leukemia.
4. Subject has active and uncontrolled autoimmune cytopenias (for 2 weeks prior to Screening), including autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP).
5. Subject has previously received venetoclax.
6. Subject is known to be positive for HIV (due to potential drug-drug interactions between antiretroviral medications and venetoclax, as well as anticipated venetoclax mechanism based lymphopenia that may potentially increase the risk of opportunistic infections).
7. Subject has received the following within 30 days prior to the first dose of venetoclax:
 A biologic agent (i.e., monoclonal antibodies) for anti-neoplastic intent.
8. Subject has received any of the following within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of venetoclax, or has not recovered to less than Common Terminology Criteria for Adverse Events (CTCAE) grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:
 Any anti-cancer therapy including chemotherapy or radiotherapy;
 Investigational therapy, including targeted small molecule agents.
9. Subject has received the following within 7 days prior to the first dose of venetoclax:
 Steroid therapy for anti-neoplastic intent;
 Strong and moderate CYP3A inhibitors;
 Strong and moderate CYP3A inducers.
10. Subject has consumed the following within 3 days prior to the first dose of venetoclax
 Grapefruit or grapefruit products;
 Seville oranges (including marmalade containing Seville oranges);
 Starfruit.
11. Subject has known allergy to both xanthine oxidase inhibitors and rasburicase.
12. Subject has a cardiovascular disability status of New York Heart Association Class ≥ 2. Class 2 is defined as cardiac disease in which subjects are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea or anginal pain.
13. Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
 Uncontrolled and/or active systemic infection (viral, bacterial, or fungal);
 Febrile neutropenia;
 Hepatitis B surface antigen (HBsAg) – positive test;
 Hepatitis B virus DNA > lower limit of quantitation;
 Chronic hepatitis C requiring treatment.
14. Subject has a significant history of cardiovascular, endocrine, hepatic, immunologic, metabolic, neurologic, psychiatric, pulmonary, or renal disease that in the opinion of the investigator would adversely affect her or his participating in this study. For subjects who have required an intervention for any of the above diseases within the past 6 months, correspondence between the investigator and the AbbVie medical monitor must occur.
15. A female subject is pregnant or breastfeeding or is considering becoming pregnant during the study or for approximately 30 days after the last dose of venetoclax.
16. Male subject who is considering fathering a child or donating sperm during the study or for approximately 90 days after the last dose of venetoclax.
17. Subject has a history of active malignancies other than CLL within the past 2 years prior to study entry, 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.
18. Subject has malabsorption syndrome or other condition that precludes enteral route of administration.

The Estimated Number of Participants

  • Taiwan

    10 participants

  • Global

    110 participants

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