Clinical Trials /

Duvelisib and Venetoclax in Relapsed or Refractory CLL or SLL or RS

NCT03534323

Description:

This research study is assessing a new drug, duvelisib, in combination with a drug that is already FDA approved, venetoclax, as a possible treatment for participants with CLL or those with Richter's Syndrome

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Richter Syndrome
  • Small Lymphocytic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Duvelisib and Venetoclax in Relapsed or Refractory CLL or SLL or RS
  • Official Title: A Phase I/II Study of Duvelisib and Venetoclax in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma or Patients With Richter's Syndrome

Clinical Trial IDs

  • ORG STUDY ID: 18-089
  • NCT ID: NCT03534323

Conditions

  • Chronic Lymphocytic Leukemia
  • Richter Syndrome

Interventions

DrugSynonymsArms
DuvelisibIPI-145Duvelisib +Venetoclax,
VenetoclaxVenclextaDuvelisib +Venetoclax,

Purpose

This research study is assessing a new drug, duvelisib, in combination with a drug that is already FDA approved, venetoclax, as a possible treatment for participants with CLL or those with Richter's Syndrome

Detailed Description

      This is a Phase I/II clinical trial. A Phase I clinical trial tests the safety of an
      investigational drugs and also tries to define the appropriate dose of the investigational
      drugs to use for further studies. "Investigational" means that the drugs are being studied
      together for the first time.

      This phase I study tests the safety of the drug duvelisib when used in combination with the
      drug venetoclax. Duvelisib is still being studied, but the FDA (the U.S. Food and Drug
      Administration) has approved the use of Duvelisib in patients with CLL/SLL with relapsed or
      refractory CLL after having received 2 or more prior therapies.

      Duvelisib is a drug that is given in capsule form and taken by mouth. This drug is designed
      to stop cancer growth by blocking a protein called phosphatidylinositide 3-kinase (PI3K),
      which is important for the survival of CLL cells. In laboratory studies and in other clinical
      trials that included participants with CLL, duvelisib was effective at killing CLL cells.

      Venetoclax is a tablet that is taken by mouth. Venetoclax targets a protein called BCL-2,
      which helps cancer cells survive. Venetoclax is an effective treatment for many participants
      with CLL who do not respond to chemotherapy or other approved drugs or who have relapsed
      after prior therapy.Venetoclax is FDA approved for participants with CLL who have never had
      therapy before or whose CLL has worsened after prior therapy.

      In the phase I portion of this study, the investigators are looking to determine the dose of
      venetoclax that is safe to give with duvelisib and to see what the side effects are of this
      combination.

      In the phase II portion of this study, we are looking to determine how effective
      thecombination of duvelisib and venetoclax is for patients with CLL or Richter's Syndrome
    

Trial Arms

NameTypeDescriptionInterventions
Duvelisib +Venetoclax,ExperimentalDuvelisib will be given alone for the first seven days. On day 8 Venetoclax will be added. Duvelisib will be administered orally twice daily Venetoclax will be administered orally daily All patients will be admitted for administration of the initial dose of venetoclax at each dose escalation
  • Duvelisib
  • Venetoclax

Eligibility Criteria

        Inclusion Criteria:

          -  Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic
             lymphoma requiring therapy, as per IW-CLL 2008 criteria OR Biopsy proven
             transformation to diffuse large B cell lymphoma (DLBCL), consistent with Richter's
             Syndrome

          -  Disease that has progressed during or relapsed after at least one previous CLL/SLL
             therapy - If Richter's Syndrome, this criterion is not applicable

          -  Age greater to or equal to 18 years

          -  ECOG performance status ≤2 (Karnofsky ≥60%)

          -  Patients must meet the following hematologic criteria at screening, unless they have
             significant bone marrow involvement of CLL confirmed on biopsy:

               -  Absolute neutrophil count ≥500 cells/mm3 (0.5 x 109/L). Growth factor is allowed
                  in order to achieve this

               -  Platelet count ≥25,000 cells/mm3 (25 x 109/L) independent of transfusion within 7
                  days of screening

          -  Adequate hepatic function defined as:

             --Serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x upper
             limit of normal (ULN), bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's
             syndrome or of non-hepatic origin

          -  Adequate renal function as defined as:

             --Serum creatinine ≤1.5 times the upper limit of normal or creatinine clearance ≥ 50
             mL/min using a 24-hour urine collection

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal, barrier method or abstinence) prior to study entry and for the duration of
             study participation

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Previous treatment with venetoclax or duvelisib

          -  Patients receiving cancer therapy (i.e., chemotherapy, radiation therapy,
             immunotherapy, biologic therapy, surgery within 2 weeks of Cycle 1/Day 1 with the
             following exceptions:

               -  For patients on targeted therapies, a washout of least five half lives is
                  required

               -  Patients who experience clinical deterioration may start therapy after a shorter
                  washout period with prior approval by the PI

               -  Corticosteroid therapy (prednisone or equivalent <20 mg daily) is allowed

          -  Confirmed central nervous system involvement

          -  Allogeneic hematologic stem cell transplant within 6 months of starting study
             treatment or active graft vs. host disease (GVHD) requiring treatment or prophylaxis

          -  History of active malignancy requiring therapy with the exception of hormonal therapy

          -  Any active systemic infection requiring IV antibiotics or uncontrolled, active
             infections

          -  Known history of human immunodeficiency virus (HIV), hepatitis C virus (HCV), or
             hepatitis B virus (HBV)

          -  Major surgery within 4 weeks of first dose of study drug

          -  Currently active gastrointestinal disease, including colitis, inflammatory bowel
             disease and diarrhea requiring therapy

          -  Currently active, clinically significant cardiovascular disease, such as uncontrolled
             arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart
             Association Functional Classification; or a history of myocardial infarction, unstable
             angina, or acute coronary syndrome within 6 months prior to randomization

          -  Any life-threatening illness, medical condition, or organ system dysfunction that, in
             the investigator's opinion, could compromise the subject's safety or put the study
             outcomes at undue risk

          -  Use of Coumadin for anticoagulation (other anticoagulants permitted)

          -  Lactating or pregnant

          -  Concurrent administration of medications or foods that are strong inhibitors or
             inducers of CYP3A (see Appendix D) . The concomitant use of drugs or foods that are
             strong or moderate inhibitors or inducers of CYP3A are not allowed beginning 1 week
             prior to the first dose of duvelisib.

          -  Patients with ongoing use of prophylactic antibiotics are eligible as long as there is
             no evidence of active infection and the antibiotic is not included on the list of
             prohibited medications

          -  Unable to swallow capsules or malabsorption syndrome, disease significantly affecting
             gastrointestinal function, or resection of the stomach or small bowel, symptomatic
             inflammatory bowel disease or ulcerative colitis, or partial or complete bowel
             obstruction resulting in malabsorption or chronic diarrhea

          -  Active abuse of alcohol

          -  History of chronic liver disease or veno-occlusive disease/sinusoidal obstruction
             syndrome

          -  History or concurrent condition of interstitial lung disease of any severity and/or
             severely impaired lung function

          -  Known hypersensitivity to duvelisib and/or its excipients

          -  History of tuberculosis treatment within the 2 years prior to initiation of therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose of Venetoclax When Administered with Duvelisib
Time Frame:Up to 7 weeks
Safety Issue:
Description:As assessed by protocol-specified DLT criteria (phase I)

Secondary Outcome Measures

Measure:Cmax
Time Frame:Up to 7 weeks
Safety Issue:
Description:Cmax
Measure:Half-life
Time Frame:Up to 7 weeks
Safety Issue:
Description:Half-life
Measure:Volume of Distribution
Time Frame:Up to 7 weeks
Safety Issue:
Description:Volume of Distribution
Measure:Objective response rate
Time Frame:2 years
Safety Issue:
Description:By IW-CLL Criteria
Measure:Duration of response
Time Frame:2 years
Safety Issue:
Description:By IW-CLL Criteria
Measure:Progression free survival
Time Frame:2 years
Safety Issue:
Description:By IW-CLL Criteria
Measure:Rate of minimal residual disease negativity
Time Frame:2 years
Safety Issue:
Description:By IW-CLL Criteria

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • chronic lymphocytic leukemia (CLL)
  • Richter's Syndrome
  • Richter's Transformation

Last Updated

November 12, 2019