DYNAMO + R: Study of Duvelisib in Combination With Rituximab vs Rituximab in Subjects With Previously Treated Follicular Lymphoma

Sponsor
SecuraBio (Industry)
Overall Status
Terminated
CT.gov ID
NCT02204982
Collaborator
(none)
13
5
2
30
2.6
0.1

Study Details

Study Description

Brief Summary

A study to evaluate the safety and efficacy of duvelisib administered in combination with rituximab vs placebo in combination with rituximab in patients with previously treated CD20-positive follicular lymphoma who are not suitable candidates for chemotherapy.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Study IPI-145-08 is an international, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 study designed to evaluate the efficacy and safety of duvelisib in combination with rituximab vs placebo in combination with rituximab in subjects with previously treated CD20-positive follicular lymphoma.

Approximately 400 subjects will receive 25 mg of duvelisib or placebo, orally BID for 28 day continuous cycles, in combination with 375 mg/m2 of Rituximab given once weekly for 4 weeks during Cycle 1 and then once on Day 1 of Cycles 4, 6, 8, and 10. Patients will remain on treatment for up to 27 cycles and may continue treatment if clinical benefit is observed.

Study Design

Study Type:
Interventional
Actual Enrollment :
13 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Duvelisib in Combination With Rituximab vs Rituximab in Subjects With Previously Treated Follicular Lymphoma
Study Start Date :
Sep 1, 2014
Actual Primary Completion Date :
Dec 1, 2016
Actual Study Completion Date :
Mar 1, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Duvelisib + Rituximab

Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg.

Drug: Duvelisib
PI3K Inhibitor
Other Names:
  • Copiktra, IPI-145
  • Drug: Rituximab
    IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10.
    Other Names:
  • Rituxan
  • MabThera
  • Placebo Comparator: Placebo + Rituximab

    Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg.

    Drug: Placebo
    Matching Placebo (25 mg BID) administered orally in 28-day continuous treatment cycles.

    Drug: Rituximab
    IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10.
    Other Names:
  • Rituxan
  • MabThera
  • Outcome Measures

    Primary Outcome Measures

    1. Progression-Free Survival (PFS) [Until disease progression, for up to 5 years from randomization]

      Due to the small number of enrolled subjects and study being terminated, PFS endpoint analysis was not performed.

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) [Until disease progression, for up to 5 years from randomization]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Diagnosis of CD20-positive FL:

    • Histology grades 1, 2 or 3a

    • Biopsy-confirmed histopathological diagnosis of FL. Biopsy specimen should be obtained ≤2 years prior to randomization, unless medically contraindicated

    • CD20 immunophenotyping performed ≤2 years prior to randomization

    • First or subsequent relapse following at least one induction therapy regimen containing rituximab in combination with an anthracycline or rituximab in combination with an alkylating agent

    • Patients in first relapse must be chemoresistant or intolerant to chemotherapy

    • No response or disease progression ≤ 24 months from start of last previous therapy

    • At least 1 measurable disease lesion >1.5 cm in at least one diameter by CT/CT-PET or magnetic resonance imaging (MRI) in an area of no prior radiation therapy, or in an area that was previously irradiated that has documented progression

    Exclusion Criteria:
    • Clinical evidence of other indolent forms of lymphoma (e.g., marginal zone lymphoma [MZL], small lymphocytic lymphoma [SLL])

    • Transformation to a more aggressive subtype of lymphoma or grade 3b FL

    • Refractory to rituximab: defined as disease progression while receiving or within 6 months of completing either weekly rituximab induction therapy, or rituximab-based chemoimmunotherapy induction

    • Intolerance to rituximab or severe allergic or anaphylactic reaction to any humanized or murine monoclonal antibodies

    • Prior allogeneic hematopoietic stem cell transplant (HSCT)

    • Known Central Nervous System (CNS) lymphoma; subjects with symptoms of CNS disease must have a negative CT scan and negative diagnostic lumbar puncture

    • Prior treatment with a PI3K inhibitor or BTK inhibitor

    • History of tuberculosis within the preceding two years

    • Ongoing systemic bacterial, fungal, or viral infections at randomization (defined as requiring IV antimicrobial, antifungal or antiviral agents)

    • Subjects on antimicrobial, antifungal or antiviral prophylaxis are not specifically excluded if all other I/E criteria are met

    • Prior, current, or chronic hepatitis B or hepatitis C infection, positive result for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) or hepatitis C virus antibodies (HCV Ab)

    • History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Frankston Victoria Australia 3199
    2 Bordeaux France 33076
    3 Bologna Italy 40138
    4 Terni Italy 05100
    5 Gdynia Poland 81-519

    Sponsors and Collaborators

    • SecuraBio

    Investigators

    • Study Chair: Hagop Youssoufian, MD, Verastem, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    SecuraBio
    ClinicalTrials.gov Identifier:
    NCT02204982
    Other Study ID Numbers:
    • IPI-145-08
    • 2013-002406-31
    First Posted:
    Jul 31, 2014
    Last Update Posted:
    Mar 17, 2021
    Last Verified:
    Mar 1, 2021
    Keywords provided by SecuraBio
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Duvelisib + Rituximab Placebo + Rituximab
    Arm/Group Description Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Duvelisib: duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Placebo: Matching Placebo (25 mg BID) administered orally in 28-day continuous treatment cycles. Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10.
    Period Title: Overall Study
    STARTED 6 7
    COMPLETED 2 0
    NOT COMPLETED 4 7

    Baseline Characteristics

    Arm/Group Title Duvelisib + Rituximab Placebo + Rituximab Total
    Arm/Group Description Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Duvelisib: duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Placebo: Matching Placebo (25 mg BID) administered orally in 28-day continuous treatment cycles. Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. Total of all reporting groups
    Overall Participants 6 7 13
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    4
    66.7%
    2
    28.6%
    6
    46.2%
    >=65 years
    2
    33.3%
    5
    71.4%
    7
    53.8%
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    56.5
    68
    68
    Sex: Female, Male (Count of Participants)
    Female
    4
    66.7%
    1
    14.3%
    5
    38.5%
    Male
    2
    33.3%
    6
    85.7%
    8
    61.5%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    1
    14.3%
    1
    7.7%
    White
    5
    83.3%
    5
    71.4%
    10
    76.9%
    More than one race
    1
    16.7%
    0
    0%
    1
    7.7%
    Unknown or Not Reported
    0
    0%
    1
    14.3%
    1
    7.7%
    Region of Enrollment (Count of Participants)
    United States
    1
    16.7%
    1
    14.3%
    2
    15.4%
    Australia
    1
    16.7%
    0
    0%
    1
    7.7%
    Italy
    2
    33.3%
    1
    14.3%
    3
    23.1%
    Spain
    1
    16.7%
    1
    14.3%
    2
    15.4%
    Poland
    1
    16.7%
    2
    28.6%
    3
    23.1%
    Canada
    0
    0%
    1
    14.3%
    1
    7.7%
    France
    0
    0%
    1
    14.3%
    1
    7.7%
    Eastern Cooperative Oncology Group Performance Status (Count of Participants)
    0=Fully active, no restrictions
    4
    66.7%
    6
    85.7%
    10
    76.9%
    1= Restricted in physically strenuous activity
    2
    33.3%
    1
    14.3%
    3
    23.1%
    2=Ambulatory more than 50% of waking hours
    0
    0%
    0
    0%
    0
    0%
    3=Confined to bed or chair more than 50% of waking
    0
    0%
    0
    0%
    0
    0%
    4=Completely disabled
    0
    0%
    0
    0%
    0
    0%
    5=Dead
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Progression-Free Survival (PFS)
    Description Due to the small number of enrolled subjects and study being terminated, PFS endpoint analysis was not performed.
    Time Frame Until disease progression, for up to 5 years from randomization

    Outcome Measure Data

    Analysis Population Description
    Data could not be reported because the study was terminated early and a sufficient number of subjects and events were not available for analysis.
    Arm/Group Title Duvelisib + Rituximab Placebo + Rituximab
    Arm/Group Description Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Duvelisib: duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Placebo: Matching Placebo (25 mg BID) administered orally in 28-day continuous treatment cycles. Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10.
    Measure Participants 0 0
    2. Secondary Outcome
    Title Overall Response Rate (ORR)
    Description
    Time Frame Until disease progression, for up to 5 years from randomization

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Duvelisib + Rituximab Placebo + Rituximab
    Arm/Group Description Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Duvelisib: duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Placebo: Matching Placebo (25 mg BID) administered orally in 28-day continuous treatment cycles. Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10.
    Measure Participants 5 6
    Complete Response
    3
    50%
    0
    0%
    Partial Response
    2
    33.3%
    1
    14.3%
    Stable Disease
    0
    0%
    3
    42.9%
    Progressive Disease
    0
    0%
    2
    28.6%

    Adverse Events

    Time Frame 15 months
    Adverse Event Reporting Description
    Arm/Group Title Duvelisib + Rituximab Placebo + Rituximab
    Arm/Group Description Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Duvelisib: duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Placebo: Matching Placebo (25 mg BID) administered orally in 28-day continuous treatment cycles. Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10.
    All Cause Mortality
    Duvelisib + Rituximab Placebo + Rituximab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/6 (0%) 0/7 (0%)
    Serious Adverse Events
    Duvelisib + Rituximab Placebo + Rituximab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/6 (83.3%) 0/7 (0%)
    Gastrointestinal disorders
    Gastrointestinal Inflammation 1/6 (16.7%) 0/7 (0%)
    General disorders
    Pyrexia 1/6 (16.7%) 0/7 (0%)
    Infections and infestations
    Pneumonia 2/6 (33.3%) 0/7 (0%)
    Pneumonia Cytomegaloviral 1/6 (16.7%) 0/7 (0%)
    Respiratory, thoracic and mediastinal disorders
    Interstitial Lung Disease 2/6 (33.3%) 0/7 (0%)
    Chronic Obstructive pulmonary disease 1/6 (16.7%) 0/7 (0%)
    Respiratory Failure 1/6 (16.7%) 0/7 (0%)
    Pneumonitis 1/6 (16.7%) 0/7 (0%)
    Other (Not Including Serious) Adverse Events
    Duvelisib + Rituximab Placebo + Rituximab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/6 (100%) 7/7 (100%)
    Blood and lymphatic system disorders
    Neutropenia 2/6 (33.3%) 0/7 (0%)
    Eye disorders
    Vision blurred 0/6 (0%) 1/7 (14.3%)
    Gastrointestinal disorders
    Abdominal pain upper 1/6 (16.7%) 0/7 (0%)
    Constipation 1/6 (16.7%) 0/7 (0%)
    Diarrhoea 1/6 (16.7%) 1/7 (14.3%)
    Dysphagia 1/6 (16.7%) 0/7 (0%)
    Gastrointestinal Inflammation 1/6 (16.7%) 0/7 (0%)
    Mouth Ulceration 1/6 (16.7%) 0/7 (0%)
    Nausea 1/6 (16.7%) 0/7 (0%)
    Abdominal distension 0/6 (0%) 1/7 (14.3%)
    Dry mouth 0/6 (0%) 1/7 (14.3%)
    General disorders
    Asthenia 2/6 (33.3%) 2/7 (28.6%)
    Chest pain 1/6 (16.7%) 0/7 (0%)
    Oedema peripheral 1/6 (16.7%) 1/7 (14.3%)
    Pyrexia 1/6 (16.7%) 1/7 (14.3%)
    Chills 0/6 (0%) 2/7 (28.6%)
    Fatigue 0/6 (0%) 2/7 (28.6%)
    Influenza like illness 0/6 (0%) 1/7 (14.3%)
    Infections and infestations
    Gastroenteritis 1/6 (16.7%) 1/7 (14.3%)
    Bronchitis 0/6 (0%) 1/7 (14.3%)
    Bronchitis viral 0/6 (0%) 1/7 (14.3%)
    Nasopharyngitis 0/6 (0%) 1/7 (14.3%)
    Oral herpes 0/6 (0%) 1/7 (14.3%)
    Upper respiratory tract infection 0/6 (0%) 2/7 (28.6%)
    Injury, poisoning and procedural complications
    Infusion related reaction 0/6 (0%) 2/7 (28.6%)
    Investigations
    Alanine aminotransferase increased 3/6 (50%) 0/7 (0%)
    Aspartate aminotransferase increased 3/6 (50%) 0/7 (0%)
    Amylase increased 1/6 (16.7%) 0/7 (0%)
    Blood Cholesterol increased 1/6 (16.7%) 0/7 (0%)
    Gamma-glutamyltransferase increased 1/6 (16.7%) 0/7 (0%)
    Lipase increased 1/6 (16.7%) 0/7 (0%)
    Weight increased 1/6 (16.7%) 0/7 (0%)
    Blood Uric acid increased 0/6 (0%) 1/7 (14.3%)
    Metabolism and nutrition disorders
    Hyperglycaemia 1/6 (16.7%) 0/7 (0%)
    Hypertriglyceridaemia 1/6 (16.7%) 0/7 (0%)
    Hyperuricaemia 1/6 (16.7%) 0/7 (0%)
    Hypokalaemia 1/6 (16.7%) 0/7 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/6 (0%) 1/7 (14.3%)
    Metatarsalgia 0/6 (0%) 1/7 (14.3%)
    Muscle spasms 0/6 (0%) 1/7 (14.3%)
    Pain in extremity 0/6 (0%) 1/7 (14.3%)
    Nervous system disorders
    Dysgeusia 1/6 (16.7%) 0/7 (0%)
    Hypoaesthesia 1/6 (16.7%) 0/7 (0%)
    Balance disorder 0/6 (0%) 1/7 (14.3%)
    Sciatica 0/6 (0%) 1/7 (14.3%)
    Psychiatric disorders
    Anxiety 0/6 (0%) 2/7 (28.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 1/6 (16.7%) 0/7 (0%)
    Dyspnoea 1/6 (16.7%) 0/7 (0%)
    Hypoventilation 1/6 (16.7%) 0/7 (0%)
    Interstitial Lung Disease 1/6 (16.7%) 0/7 (0%)
    Productive cough 0/6 (0%) 1/7 (14.3%)
    Skin and subcutaneous tissue disorders
    Rash 1/6 (16.7%) 0/7 (0%)
    Pruritis 0/6 (0%) 1/7 (14.3%)
    Skin Discolouration 0/6 (0%) 1/7 (14.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Gloria Patrick
    Organization Verastem, Inc.
    Phone 1-781-469-1594
    Email gpatrick@verastem.com
    Responsible Party:
    SecuraBio
    ClinicalTrials.gov Identifier:
    NCT02204982
    Other Study ID Numbers:
    • IPI-145-08
    • 2013-002406-31
    First Posted:
    Jul 31, 2014
    Last Update Posted:
    Mar 17, 2021
    Last Verified:
    Mar 1, 2021