Clinical Trials /

A Study of Venetoclax and Rituximab/Hyaluronidase Human in Relapsed/Refractory CLL

NCT03467867

Description:

This is an open-label, multicenter, Phase II study to investigate the efficacy and safety of venetoclax in combination with Rituximab/hyaluronidase human in participants with relapsed or refractory chronic lymphocytic leukemia (CLL).

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Venetoclax and Rituximab/Hyaluronidase Human in Relapsed/Refractory CLL
  • Official Title: A Phase II Study of Venetoclax and Rituximab/Hyaluronidase Human in Relapsed/Refractory CLL

Clinical Trial IDs

  • ORG STUDY ID: 2017-1502
  • NCT ID: NCT03467867

Conditions

  • Chronic Lymphocytic Leukemia

Interventions

DrugSynonymsArms
VenetoclaxGDC-0199, ABT-199Venetoclax + Rituximab
RituximabRituxanVenetoclax + Rituximab
Rituximab/Hyaluronidase HumanRituxan HycelaVenetoclax + Rituximab

Purpose

This is an open-label, multicenter, Phase II study to investigate the efficacy and safety of venetoclax in combination with Rituximab/hyaluronidase human in participants with relapsed or refractory chronic lymphocytic leukemia (CLL).

Detailed Description

      The study has one arm and all the patients will receive venetoclax and rituximab.
    

Trial Arms

NameTypeDescriptionInterventions
Venetoclax + RituximabExperimentalParticipants will be initially placed in a venetoclax 5 weeks ramp-up period, and will be administered an initial 20 mg oral tablet dose once daily (QD), incrementing weekly up to a maximum dose of 400 mg. Participants will then continue taking venetoclax 400 mg QD from Week 5 onwards, as directed by the investigator in combination with rituximab 375 mg/m^2 IV on Day 1 of Cycle 1 followed by 13.4 mL of rituximab SC 1,600 mg/26,800 Units vial (1,600 mg rituximab and 26,800 Units hyaluronidase human) on Day 1 of Cycle 2-6.
  • Venetoclax
  • Rituximab
  • Rituximab/Hyaluronidase Human

Eligibility Criteria

        Inclusion Criteria:

          -  Signed Informed Consent Form

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

          -  Patient must have diagnosis of CLL that meets published 2008 IWCLL NCI-WG criteria.

          -  Patient must have relapsed/refractory disease with an indication for treatment.

          -  Patient must have an Eastern Cooperative Oncology Group (ECOG) performance score of ≤
             2

          -  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 lymphoma per the investigator) defined as follows:

               -  Hemoglobin (> / =) 9 g/dL

               -  Absolute neutrophil count (> / =) 1.0 x 109/L

               -  Platelet count (> / =)75 x 109/L

          -  Adequate renal function, as indicated by:

               -  Calculated creatinine clearance ≥ 30 mL/min using 24-hour Creatinine Clearance or
                  modified Cockcroft-Gault equation (eCCR; with the use of ideal body mass [IBM]
                  instead of mass)

          -  Adequate liver function, as indicated by:

               -  AST or ALT (< / =) 2.5 x ULN

               -  Total bilirubin < 1.5 x ULN (or (< / =) 3 x ULN for patients with documented
                  Gilbert syndrome)

          -  Female patients who are not of child-bearing potential and female patients of
             child-bearing potential who have a negative serum pregnancy test within 3 days prior
             to Cycle 1, Day 1.

          -  Patients with HIV infection could be included in the study, as long as their disease
             is under control on anti-retroviral therapy. Precautions should be taken to modify
             their HAART regimen to minimize drug interaction

          -  Warfarin is considered a cautionary medication. Patients on warfarin will be
             encouraged to replace warfarin with other anticoagulants if possible. If it is not
             possible or patient is not willing to switch, they could still be included in the
             study with caution.

        Exclusion Criteria:

          -  Known hypersensitivity to any of the study drugs

          -  Allogeneic stem cell transplant within the past 1 year.

          -  Richter's transformation confirmed by biopsy

          -  History of other malignancy that could affect compliance with the protocol or
             interpretation of results

               -  Patients with a history of curatively treated basal or squamous cell carcinoma or
                  Stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible.

               -  Patients with a malignancy that has been treated with surgery alone with curative
                  intent will be included. Individuals in documented remission without treatment
                  for (> / =) 2 years prior to enrollment may be included at the discretion of the
                  investigator.

          -  Evidence of significant, uncontrolled concomitant diseases that could affect
             compliance with the protocol or interpretation of results or that could increase risk
             to the patient, including renal disease that would preclude chemotherapy
             administration or pulmonary disease (including obstructive pulmonary disease and
             history of bronchospasm)

          -  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

          -  Received the following agents 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

               -  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 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.

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

          -  Patients with uncontrolled HIV infection

          -  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 serum pregnancy test result within 21 days
             prior to initiation of study drug.

          -  Recent major surgery (within 6 weeks prior to the start of Cycle 1, Day 1) other than
             for diagnosis

          -  Malabsorption syndrome or other condition that precludes enteral route of
             administration

          -  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:Overall Response Rate (ORR)
Time Frame:Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)
Safety Issue:
Description:Percentage of Participants With Best Overall Response (OR)(Defined as Complete Response [CR], Initial CR [CRi], Nodular Partial Response [nPR], PR) as Assessed by Investigator Determined Using iwCLL Guidelines

Secondary Outcome Measures

Measure:Disease Response
Time Frame:12 weeks after Day 1 of last cycle of combination therapy (approximately 5 years, cycle length= 28 days)
Safety Issue:
Description:Percentage of Participants With Disease Response (OR, CR, CRi, nPR, PR) as Assessed by Investigator Determined Using iwCLL Guidelines at end of Combination Treatment Visit
Measure:Duration of Responses (DOR)
Time Frame:Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)
Safety Issue:
Description:Duration of Responses (DOR)
Measure:Time to Progression (TTP)
Time Frame:Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)
Safety Issue:
Description:Time to progression will be defined as the time from the date of first dose (date of enrollment if not dosed) to the date of earliest disease progression (per the investigator assessment).
Measure:Progression-Free Survival (PFS)
Time Frame:Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]
Safety Issue:
Description:Investigator-Assessed Progression-Free Survival (PFS) Determined Using Standard International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines
Measure:Overall Survival (OS)
Time Frame:Baseline up to death (up to approximately 5 years)
Safety Issue:
Description:Overall Survival (OS)
Measure:Time to Next Anti-CLL Treatment (TTNT)
Time Frame:Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]
Safety Issue:
Description:Time to Next Anti-CLL Treatment (TTNT)
Measure:Percentage of Participants With Minimal Residual Disease (MRD)
Time Frame:12 weeks after Day 1 of last cycle of combination therapy (up to approximately 5 years, cycle length= 28 days) ]
Safety Issue:
Description:Percentage of Participants With Minimal Residual Disease (MRD) Negativity at End of Combination Treatment Response Visit

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Georgetown University

Trial Keywords

  • Chronic Lymphocytic Leukemia
  • Leukemia
  • Venetoclax
  • Rituximab
  • Lymphoid
  • Lymphoproliferative Disorders
  • Antineoplastic Agents
  • Neoplasm

Last Updated

July 29, 2019