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

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ClinicalTrials.gov Identifier: NCT03467867
Recruitment Status : Recruiting
First Posted : March 16, 2018
Last Update Posted : July 31, 2019
Sponsor:
Collaborator:
Hackensack Meridian Health
Information provided by (Responsible Party):
Maryam S. Yazdy, MD, Georgetown University

Tracking Information
First Submitted Date  ICMJE March 12, 2018
First Posted Date  ICMJE March 16, 2018
Last Update Posted Date July 31, 2019
Actual Study Start Date  ICMJE April 26, 2018
Estimated Primary Completion Date October 15, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 15, 2018)
Overall Response Rate (ORR) [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03467867 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2018)
  • Disease Response [ Time Frame: 12 weeks after Day 1 of last cycle of combination therapy (approximately 5 years, cycle length= 28 days) ]
    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
  • Duration of Responses (DOR) [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]
    Duration of Responses (DOR)
  • Time to Progression (TTP) [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ]
    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).
  • Progression-Free Survival (PFS) [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ] ]
    Investigator-Assessed Progression-Free Survival (PFS) Determined Using Standard International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines
  • Overall Survival (OS) [ Time Frame: Baseline up to death (up to approximately 5 years) ]
    Overall Survival (OS)
  • Time to Next Anti-CLL Treatment (TTNT) [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 5 years) ] ]
    Time to Next Anti-CLL Treatment (TTNT)
  • 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) ] ]
    Percentage of Participants With Minimal Residual Disease (MRD) Negativity at End of Combination Treatment Response Visit
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Venetoclax and Rituximab/Hyaluronidase Human in Relapsed/Refractory CLL
Official Title  ICMJE A Phase II Study of Venetoclax and Rituximab/Hyaluronidase Human in Relapsed/Refractory CLL
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Lymphocytic Leukemia
Intervention  ICMJE
  • Drug: Venetoclax
    Venetoclax will be administered as described in the reporting arm.
    Other Names:
    • GDC-0199
    • ABT-199
  • Drug: Rituximab
    Rituximab (IV) will be administered as described in the reporting arm.
    Other Name: Rituxan
  • Drug: Rituximab/Hyaluronidase Human
    Rituximab/Hyaluronidase Human (SC) ill be administered as described in the reporting arm.
    Other Name: Rituxan Hycela
Study Arms  ICMJE Experimental: Venetoclax + Rituximab
Participants 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.
Interventions:
  • Drug: Venetoclax
  • Drug: Rituximab
  • Drug: Rituximab/Hyaluronidase Human
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 15, 2018)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 15, 2023
Estimated Primary Completion Date October 15, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jenny Crawford, RN 202-687-0893 crawfojg@georgetown.edu
Contact: Pari Ramzi, RN 202-687-0038 ramzip1@georgetown.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03467867
Other Study ID Numbers  ICMJE 2017-1502
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Maryam S. Yazdy, MD, Georgetown University
Study Sponsor  ICMJE Georgetown University
Collaborators  ICMJE Hackensack Meridian Health
Investigators  ICMJE Not Provided
PRS Account Georgetown University
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP