Clinical Trials /

Intermittent Duvelisib Dosing in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT03961672

Description:

This phase II trial studies how well duvelisib on an intermittent (irregular) dosing schedule works in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Duvelisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving duvelisib on an intermittent schedule may result in similar effectiveness with less amount of severe side effects.

Related Conditions:
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Intermittent Duvelisib Dosing in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
  • Official Title: A Phase II Study of Intermittent Duvelisib Dosing in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Clinical Trial IDs

  • ORG STUDY ID: STUDY00019402
  • SECONDARY ID: NCI-2019-02789
  • SECONDARY ID: HEM-19009-LM
  • SECONDARY ID: STUDY00019402
  • SECONDARY ID: P30CA069533
  • NCT ID: NCT03961672

Conditions

  • Recurrent Chronic Lymphocytic Leukemia
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Small Lymphocytic Lymphoma

Interventions

DrugSynonymsArms
Duvelisib8-Chloro-2-phenyl-3-((1S)-1-(7H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one, INK-1197, IPI-145Treatment (duvelisib)

Purpose

This phase II trial studies how well duvelisib on an intermittent (irregular) dosing schedule works in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Duvelisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving duvelisib on an intermittent schedule may result in similar effectiveness with less amount of severe side effects.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the efficacy of duvelisib (induction followed by maintenance [intermittent
      dosing]) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), as
      measured by the progression free survival (PFS).

      SECONDARY OBJECTIVES:

      I. To evaluate safety of duvelisib induction and maintenance (by intermittent dosing) in
      relapsed/refractory CLL.

      II. To evaluate clinical benefits to duvelisib treatment.

      EXPLORATORY OBJECTIVES:

      I. To evaluate T-cell populations in patients with CLL treated with duvelisib.

      OUTLINE:

      INDUCTION: Patients receive duvelisib orally (PO) twice daily (BID) on days 1-28. Cycles
      repeat every 28 days for 12 weeks in the absence of disease progression or unacceptable
      toxicity.

      MAINTENANCE: Patients receive duvelisib PO BID on days 1-2, 8-9, 15-16, and 22-23. Cycles
      repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for up to 12
      months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (duvelisib)ExperimentalINDUCTION: Patients receive duvelisib PO BID on days 1-28. Cycles repeat every 28 days for 12 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive duvelisib PO BID on days 1-2, 8-9, 15-16, and 22-23. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Duvelisib

Eligibility Criteria

        Inclusion Criteria:

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

          -  Histologically or flow cytometry confirmed diagnosis of B-CLL/small lymphocytic
             lymphoma (SLL) according to National Cancer Institute - Working Group (NCI-WG) 1996
             guidelines. Patients who lack CD23 expression on their leukemia cells should be
             examined for (and found NOT to have) either t(11;14) or cyclin D1 overexpression, to
             rule out mantle cell lymphoma.

          -  Participants have undergone >= 1 prior chemotherapy-based or immunotherapy-based
             regimen or targeted therapy (e.g., inhibitors of BTK [e.g., ibrutinib], or BCL2 [e.g.,
             venetoclax]) administered for >= 2 cycles (>= 8 weeks for oral therapies), and have
             had either documented disease progression or no response (i.e., stable disease [SD])
             to the most recent treatment regimen.

               -  Note: Individuals intolerant to ibrutinib therapy and those who progress on
                  ibrutinib are eligible as long as they satisfy the above criteria.

          -  Patients with CLL/SLL must demonstrate active disease meeting at least 1 of the
             International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for
             requiring treatment:

               -  A minimum of any one of the following constitutional symptoms:

                    -  Unintentional weight loss > 10% within the previous 6 months prior to
                       screening.

                    -  Extreme fatigue (unable to work or perform usual activities).

                    -  Fevers of greater than 100.5 degrees Fahrenheit (F) for >= 2 weeks without
                       evidence of infection.

                    -  Night sweats without evidence of infection.

               -  Evidence of progressive marrow failure as manifested by the development of, or
                  worsening of anemia or thrombocytopenia.

               -  Massive (i.e., > 6 cm below the left costal margin), progressive or symptomatic
                  splenomegaly.

               -  Massive nodes or clusters (i.e., > 10 cm in longest diameter) or progressive
                  lymphadenopathy.

               -  Progressive lymphocytosis with an increase of > 50% over a 2-month period, or an
                  anticipated doubling time of less than 6 months.

               -  Autoimmune anemia or thrombocytopenia that is poorly responsive to
                  corticosteroids.

          -  Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 2.

          -  Direct bilirubin =< 2 x institutional upper limit of normal (ULN); unless due to known
             Gilbert?s syndrome or compensated hemolysis directly attributable to CLL (prior to
             starting study drug).

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) less than 2.5 x
             institutional ULN (prior to starting study drug).

          -  Estimated creatinine clearance (CrCL) using the Cockcroft-Gault equation (or an
             alternative equation, per institutional standard) >= 30 mL/min (prior to starting
             study drug).

          -  Platelets >= 30,000/mm^3 independent of transfusion support, with no active bleeding,
             and absolute neutrophil count (ANC) >= 500/mm^3, unless due to disease involvement in
             the bone marrow (prior to starting study drug).

          -  Participant must be able to swallow tablets or capsules. A participant with any
             gastrointestinal disease that would impair ability to swallow, retain, or absorb drug
             is not eligible.

          -  Female participants of childbearing potential (defined as a sexually mature woman who
             has not undergone surgical sterilization or who has not been naturally postmenopausal
             for at least 12 consecutive months for women > 55 years of age) must have a negative
             urine or serum pregnancy test within 72 hours prior to receiving the first dose of
             study medication. If the urine test is positive or cannot be confirmed as negative, a
             serum pregnancy test will be required.

          -  Female participants of childbearing potential must agree to use adequate methods of
             contraception starting with the first dose of study therapy through 60 days after the
             last dose of study therapy.

               -  Participants of childbearing potential are those who have not been surgically
                  sterilized or have not been free from menses for > 1 year without an alternative
                  medical cause.

          -  Male participants must agree to use an adequate method of contraception starting with
             the first dose of study therapy through 60 days after the last dose of study therapy.

        Exclusion Criteria:

          -  Prior therapeutic intervention with any of the following:

               -  Therapeutic anticancer antibodies within 4 weeks;

               -  Radio- or toxin-immunoconjugates within 10 weeks;

               -  Inhibitors of Bruton tyrosine kinase (BTK) (e.g., ibrutinib), BH3-mimetic
                  venetoclax, lenalidomide and other ?targeted? therapy ? within 6 half-lives
                  (i.e., 36 hours for ibrutinib)

               -  All other chemotherapy, radiation therapy within 3 weeks prior to initiation of
                  therapy.

               -  PI3K inhibitors (idelalisib, copanlisib or any investigational PI3K inhibitor
                  including duvelisib and umbralisib) at any time.

          -  Inadequate recovery from adverse events related to prior therapy to grade =< 1
             (excluding grade 2 alopecia and neuropathy).

          -  Chronic use of corticosteroids in excess of prednisone 30 mg/day or its equivalent.

          -  Allogeneic stem cell transplant within the past 12 months, or ongoing
             immunosuppressive therapy other than prednisone =< 10 mg/day (or equivalent).

          -  Use of strong CYP3A4 inhibitors or inducers, in the one week prior to initiating study
             treatment or concomitant.

          -  Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV),
             or herpes zoster (varicella zoster virus [VZV]) at screening.

          -  History of prior malignancy except:

               -  Malignancy treated with curative intent and no known active disease present for
                  >= 2 years prior to initiation of therapy on current study;

               -  Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ)
                  without evidence of disease;

               -  Adequately treated in situ carcinomas (e.g., breast, cervical, esophageal, etc.)
                  without evidence of disease;

               -  Asymptomatic prostate cancer managed with ?watch and wait? strategy

          -  Uncontrolled immune hemolysis or thrombocytopenia (positive direct antiglobulin test
             in absence of hemolysis or history of immune-mediated cytopenias are not exclusions).

          -  History of human immunodeficiency virus (HIV) infection or active hepatitis B or C.

          -  History of chronic liver disease.

          -  Major surgery (requiring general anesthesia) within 2 weeks prior to initiation of
             therapy.

          -  Patients with clinically significant medical condition of malabsorption, inflammatory
             bowel disease, chronic conditions which manifest with diarrhea, refractory nausea,
             vomiting or any other condition that will interfere significantly with drug
             absorption.

          -  History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia
             requiring medication or a pacemaker within the last 6 months prior to screening.

          -  Baseline QT interval corrected with Fridericia?s method (QTcF) > 500 ms. (NOTE:
             criterion does not apply to subjects with a right or left bundle branch block BBB).

          -  Active uncontrolled infection.

          -  Psychiatric illness/social situations that would limit compliance with study
             requirements.

          -  Participant is pregnant or breastfeeding, or expecting to conceive or father children
             within the projected duration of the trial, starting with the screening visit through
             120 days after the last dose of trial treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of progression free survival (PFS) at 12 months
Time Frame:First dose of duvelisib until death, time of progression, start of new therapy, or 12 months from start of therapy, whichever occurs first
Safety Issue:
Description:Proportion of subjects achieving 12 month PFS will be estimated along with a two-sided exact Clopper-Pearson 95% confidence interval.

Secondary Outcome Measures

Measure:Objective response rate (ORR) (including complete response [CR] and partial response [PR])
Time Frame:First dose of duvelisib up to 12 months after discontinuation of duvelisib
Safety Issue:
Description:Probability of having ORR will be measured and reported (if available) with 95% exact confidence interval.
Measure:Median PFS
Time Frame:First dose of duvelisib until death, time of progression, or start of new therapy, whichever occurs first, assessed up to 12 months after discontinuation of duvelisib
Safety Issue:
Description:Estimated distribution of the PFS will be plotted using Kaplan Meier curves and reported with median PFS and 95% confidence intervals if available.
Measure:Duration of response (DOR)
Time Frame:From time of ORR until death, time of progression, start of new therapy, or end of follow-up, whichever occurs first, assessed up to 12 months after discontinuation of duvelisib
Safety Issue:
Description:Descriptive statistics of DOR including mean, median, minimum, maximum, standard deviation, and 95% confidence interval will be reported.
Measure:Incidence of toxicity (per Common Terminology Criteria for Adverse Events version 5.0 [CTCAE v5.0])
Time Frame:From first dose of duvelisib until 3 months post-discontinuation of duvelisib
Safety Issue:
Description:Incidence of having grade 3+ acute toxicity will be determined for participants with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) that received at least one dose of duvelisib. The 95% confidence interval will be reported with the point estimate of toxicity rate.
Measure:Duration of therapy
Time Frame:From first dose of duvelisib until time of duvelisib discontinuation (up to 5 years)
Safety Issue:
Description:Estimate the duration of therapy from the first dose of study drug until therapy is discontinued for any reason. The proportion of subjects completing the induction phase will be reported including 95% confidence interval. Proportion who move prematurely to maintenance phase will be reported.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:OHSU Knight Cancer Institute

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