Clinical Trials /

The Combination of Venetoclax and Obinutuzumab in People With Chronic Lymphocytic Leukemia (CLL)

NCT04447768

Description:

This study will help researchers collect more information about how effective the combination of venetoclax and obinutuzumab is in treating CLL in people who have not received a previous treatment for their cancer.

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: The Combination of Venetoclax and Obinutuzumab in People With Chronic Lymphocytic Leukemia (CLL)
  • Official Title: A Phase II: Venetoclax-Based Therapy for the Treatment of Fit Patients With Chronic Lymphocytic Leukemia (CLL) in the Front-Line Setting

Clinical Trial IDs

  • ORG STUDY ID: 20-044
  • NCT ID: NCT04447768

Conditions

  • Chronic Lymphocytic Leukemia (CLL)

Interventions

DrugSynonymsArms
ObinutuzumabVenetoclax and Obinutuzumab
VenetoclaxVenetoclax and Obinutuzumab

Purpose

This study will help researchers collect more information about how effective the combination of venetoclax and obinutuzumab is in treating CLL in people who have not received a previous treatment for their cancer.

Trial Arms

NameTypeDescriptionInterventions
Venetoclax and ObinutuzumabExperimentalAll patients will receive a minimum of 12 cycles (cycle = 28 days) of therapy with venetoclax and obinutuzumab during the treatment period. For patients who remain MRD positive at Cycle 12 of therapy, an additional 12 cycles of venetoclax monotherapy will be given.
  • Obinutuzumab
  • Venetoclax

Eligibility Criteria

        Inclusion Criteria:

          -  Signed informed consent form.

          -  Ability and willingness to comply with the requirements of the study protocol.

          -  Age ≥18 years.

          -  Have documented previously untreated chronic lymphocytic leukemia according to iwCLL /
             WHO criteria.

          -  Require treatment of CLL per iwCLL guidelines.

          -  CIRS score ≤ 6.

          -  Eastern Cooperative Oncology Group Performance Status of 0 or 1.

          -  Adequate hematologic function (unless caused by underlying disease, as established by
             extensive bone marrow involvement or as a result of hypersplenism secondary to the
             involvement of the spleen by CLL per the investigator) defined as follows:

               -  Hemoglobin ≥ 8 g/dL without transfusion support, unless anemia is due to marrow
                  involvement of CLL.

               -  Absolute neutrophil count ≥ 1.0 x 10^9/L.

               -  Platelet count ≥ 30 x 109/L; in cases of thrombocytopenia clearly due to marrow
                  involvement of CLL (per the discretion of the investigator), platelet count
                  should be ≥ 10 x 109/L if there is bone marrow involvement.

          -  Adequate renal function, as indicated by modified Cockcroft-Gault equation (eCCR; with
             the use of ideal body mass [IBM] instead of mass) of > 70mL/min

          -  Adequate liver function, as indicated by:

               -  AST or ALT ≤ 2.5 x ULN.

               -  Total bilirubin ≤ 1.5 x ULN (or ≤ 5 x ULN for patients with documented Gilbert
                  syndrome).

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use a contraceptive method with a failure rate of < 1%
             per year during the treatment period and for at least 30 days after the last dose of
             venetoclax or 18 months after the last dose of obinutuzumab, whichever is longer.

               -  Women must refrain from donating eggs during this same period.

               -  A woman is considered to be of childbearing potential if she is postmenarcheal,
                  has not reached a postmenopausal state (> 12 continuous months of amenorrhea with
                  no identified cause other than menopause), and has not undergone surgical
                  sterilization (removal of ovaries and/or uterus).

               -  Examples of contraceptive methods with a failure rate of < 1% per year include
                  bilateral tubal ligation, male sterilization, hormonal contraceptives that
                  inhibit ovulation, hormone-releasing intrauterine devices, and copper
                  intrauterine devices.

               -  The reliability of sexual abstinence should be evaluated in relation to the
                  duration of the clinical trial and the preferred and usual lifestyle of the
                  patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
                  postovulation methods) and withdrawal are not acceptable methods of
                  contraception.

          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             contraceptive measures, and agreement to refrain from donating sperm, as defined
             below:

               -  With female partners of childbearing potential, men must remain abstinent or use
                  a condom plus an additional contraceptive method that together result in a
                  failure rate of < 1% per year during the treatment period and for at least 90
                  days after the last dose of venetoclax or 18 months after the last dose of
                  obinutuzumab, whichever is longer. Men must refrain from donating sperm during
                  this same period.

               -  With pregnant female partners, men must remain abstinent or use a condom for the
                  duration of the pregnancy to avoid exposing the embryo.

               -  The reliability of sexual abstinence should be evaluated in relation to the
                  duration of the clinical trial and the preferred and usual lifestyle of the
                  patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
                  postovulation methods) and withdrawal are not acceptable methods of
                  contraception.

        Exclusion Criteria:

          -  Prior CLL-directed therapy. Patients may have received a brief (≤7 days) course of
             systemic steroids prior to initiation of study therapy for control of lymphoma-related
             symptoms.

          -  Transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic
             leukemia).

          -  Known hypersensitivity to any of the study drugs.

          -  History of prior malignancy, except for conditions as listed below if patients have
             recovered from the acute side effects incurred as a result of previous therapy:

               -  Malignancies surgically treated with curative intent and with no known active
                  disease present for < 2 years

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease (no time constraint).

               -  Adequately treated cervical carcinoma in situ without evidence of disease (no
                  time constraint).

               -  Surgically/adequately treated low grade, early stage, localized prostate cancer
                  without evidence of disease (no time constraint).

          -  Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
             (excluding fungal infections of nail beds) at study enrollment, or any major episode
             of infection requiring treatment with IV antibiotics or hospitalization (relating to
             the completion of the course of antibiotics) within 4 weeks prior to Cycle 1 Day 1.

          -  Requires the use of warfarin (because of potential drug-drug interactions that may
             potentially increase the exposure of warfarin).

          -  Received the following agents within 7 days prior to the first dose of venetoclax:

               -  Steroid therapy >20 mg of prednisone for anti-neoplastic intent.

               -  Strong and moderate CYP3A inhibitors.

               -  Strong and moderate CYP3A inducers.

               -  Consumed grapefruit, grapefruit products, Seville oranges (including marmalade
                  containing Seville oranges), or star fruit within 3 days prior to the first dose
                  of venetoclax.

          -  Clinically significant history of liver disease, including active viral or other
             hepatitis, current alcohol abuse, or cirrhosis

          -  Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface
             antigen (HBsAg), or hepatitis C (HCV) antibody

               -  Patients who are positive for HCV antibody must be negative for HCV by polymerase
                  chain reaction (PCR) to be eligible for study participation

               -  Patients with occult or prior HBV infection (defined as positive total hepatitis
                  B core antibody [HBcAb] and negative HBsAg) may be included if HBV DNA is
                  undetectable. These patients must be willing to undergo monthly DNA testing and
                  should consider antiviral prophylaxis as per institutional standards.

          -  Known infection with HIV or human T-cell leukemia virus 1 (HTLV-1)

          -  Receipt of live-virus vaccines within 28 days prior to the initiation of study
             treatment or need for live-virus vaccines at any time during study treatment

          -  Pregnant or lactating, or intending to become pregnant during the study

             °Women of childbearing potential must have a negative pregnancy test result within 21
             days prior to initiation of study drug.

          -  Recent major surgery (within 4 weeks prior to the start of Cycle 1, Day 1) other than
             for diagnosis.

          -  Inability to swallow a large number of tablets.

          -  Malabsorption syndrome or other condition that precludes enteral route of
             administration. This is subject to investigator discretion.

          -  Known allergy to both xanthine oxidase inhibitors and rasburicase.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:progression-free survival (PFS)
Time Frame:36 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:2 years
Safety Issue:
Description:Overall response rate (ORR) is defined as the proportion of patients with a best overall response of partial response (PR) or complete response (CR). Patients who do not have a tumor response assessment for any reason will be considered non-responders and will be included in the denominator when calculating the ORR.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Venetoclax
  • Obinutuzumab
  • 20-044

Last Updated

June 24, 2020