A Phase I/Ib Safety and Efficacy Study of the PI3K-delta Inhibitor TGR-1202 and Ibrutinib in Patients With CLL or MCL

Sponsor
Dana-Farber Cancer Institute (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02268851
Collaborator
TG Therapeutics, Inc. (Industry), The Leukemia and Lymphoma Society (Other), Blood Cancer Research Partnership (Other)
45
Enrollment
6
Locations
2
Arms
107
Duration (Months)
7.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This research study will be evaluating the safety and efficacy of a study drug called TGR-1202 in combination with a known drug ibrutinib, also known as Imbruvica, as a possible treatment for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Mantle Cell Lymphoma (MCL) that has come back or that has not responded to standard treatment.

Detailed Description

This research study is a Phase I and Ib combination clinical trial, which aims to both evaluate the safety of an investigational drug combination and also tries to define the appropriate dose of the investigational drug to evaluate in later clinical trials. "Investigational" means that the intervention is being studied. It also means that the FDA (U.S. Food and Drug Administration) has not approved TGR-1202 in the United States for use in MCL/CLL/SLL cancers.

TGR-1202 is a newly developed drug that may stop cancer cells from growing based on recent laboratory experiments. The results from these experiments suggest this drug may help to kill cancer cells when coupled with ibrutinib. In this research study, the safety and tolerability of TGR-1202 is being investigated to determine the highest dose that can safely be used in combination with ibrutinib. The study is also aimed to evaluate whether TGR-1202 has any effect on tumor growth (nodal response), and to determine the overall repsonse rate and duration of response in patients with CLL/SLL or MCL

Study Design

Study Type:
Interventional
Actual Enrollment :
45 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multi-center Phase I/Ib Study Evaluating the Efficacy and Safety of the Novel PI3k Delta Inhibitor TGR-1202 in Combination With Ibrutinib in Patients With Select B-Cell Malignancies
Study Start Date :
Nov 1, 2014
Actual Primary Completion Date :
May 1, 2018
Anticipated Study Completion Date :
Oct 1, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: CLL

Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. Each Cycle = 28 days TGR-1202 (oral): Starting on Day 1 administered daily. Ibrutinib (oral): Starting on Day 1 administered daily.

Drug: TGR-1202
Capsules taken whole daily with water and with food
Other Names:
  • RP5264
  • Umbralisib
  • Drug: Ibrutinib
    Capsules taken whole with water- Do not consume fish oil, vitamin E, grapefruit, or Seville oranges
    Other Names:
  • Imbruvica
  • CRA-032765
  • PCI-32765
  • Experimental: MCL

    Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. Each Cycle = 28 days TGR-1202 (oral): Starting on Day 1 administered daily. Ibrutinib (oral): Starting on Day 1 administered daily.

    Drug: TGR-1202
    Capsules taken whole daily with water and with food
    Other Names:
  • RP5264
  • Umbralisib
  • Drug: Ibrutinib
    Capsules taken whole with water- Do not consume fish oil, vitamin E, grapefruit, or Seville oranges
    Other Names:
  • Imbruvica
  • CRA-032765
  • PCI-32765
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Patients Who Experienced a Dose Limiting Toxicity (DLT) During Phase I [Participants were assessed every week or more often as needed during Cycle 1 or more often for up to 28 days to assess Dose-limiting toxicities (DLTs) during Phase I]

      To assess the safety of TGR1202 in combination with ibrutinib relapsed or refractory CLL or MCL. DLT is based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. DLT refers to toxicities experienced at any time during the study treatment, defined as Grade 4 anemia; Grade 4 neutropenia lasting >7 days (while receiving growth factor support); Grade 4 thrombocytopenia lasting > 7 days; Grade ≥3 febrile neutropenia; and Grade ≥3 thrombocytopenia with Grade >2 hemorrhage;Grade ≥ 3 non-hematologic toxicity unresponsive to standard supportive care measure with the exception of asymptomatic Grade ≥3 lab abnormalities that resolve to ≤ Grade 1 or baseline within 7 days;treatment delay of ≥14 days due to unresolved toxicity; and non-hematologic toxicity of Grade 2 (at any time during treatment) that, in the judgment of the Investigators, Study Chair, and the Medical Monitor, is dose-limiting.

    Secondary Outcome Measures

    1. Overall Response Rate [At baseline, End of Cycle 2, End of Cycle 5, End of Cycle 9, End of Cycle 14 and approximately q6 months until C26, then investigator discretion thereafter]

      Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008) by Lugano Criteria ( Cheson et al,.24) for MCL

    2. Rate of Nodal Response With Lymphocytosis (nPR) [2 years]

    3. Rate of Progression Free Survival [2 Years]

    4. Duration of Response [2 Years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Confirmed diagnosis of Mantle Cell Lymphoma (MCL), Chronic Lymphocytic Leukemia (CLL), or Small Lymphocytic Lymphoma (SLL)

    • Adequate organ system function ( Absolute neutrophil count, Platelets,Bilirubin, Platelets, Aspartate transferase ,Alanine aminotransferase, Creatinine Clearance)

    • Eastern Cooperative Group (ECOG) Performance status ≤ 2

    • Ability to swallow and retain oral medication

    • Female patients: must have negative serum pregnancy test at study screening/ all male partners must consent to use a medically acceptable method of contraception

    • Willingness and ability to comply with trial and follow-up procedures, and give written informed consent

    Exclusion Criteria:-

    • Patients receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization) within 3 weeks of Cycle 1/Day 1,

    • Autologous hematologic stem cell transplant within 3 months of study entry.

    • Allogeneic hematologic stem cell transplant within 12 months.

    • Post-allo patients must not have active graft versus-host disease

    • Evidence of active Hepatitis B,Hepatitis C or HIV infection.

    • Active central nervous system involvement by lymphoma

    • Requires treatment with strong CYP3A4/5 inhibitors

    • Severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study

    • QTcF >470 msec (QT interval, Fredericia calculation)

    • Angina not well-controlled by medication

    • Poorly controlled or clinically significant atherosclerotic vascular disease

    • Presence of other active cancers, or history of treatment for invasive cancer within the past 2 years.

    • Require warfarin for anticoagulation

    • Women who are pregnant or lactating

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Pacific Cancer CareMontereyCaliforniaUnited States93940
    2St. Francis Hospital and Cancer CenterHartfordConnecticutUnited States06105
    3Eastern Maine Medical Center/ Northern Light Cancer CareBrewerMaineUnited States04412
    4Dana Farber Cancer InstituteBostonMassachusettsUnited States02115
    5Beth Israel Deaconness Medical CenterBostonMassachusettsUnited States02215
    6West Michigan Cancer CenterKalamazooMichiganUnited States49007

    Sponsors and Collaborators

    • Dana-Farber Cancer Institute
    • TG Therapeutics, Inc.
    • The Leukemia and Lymphoma Society
    • Blood Cancer Research Partnership

    Investigators

    • Principal Investigator: Matthew Davids, MD, Dana-Farber Cancer Institute

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Matthew S. Davids, MD, Principal Investigators, Dana-Farber Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT02268851
    Other Study ID Numbers:
    • 14-396
    • TGR-IB-105
    First Posted:
    Oct 20, 2014
    Last Update Posted:
    Oct 4, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Matthew S. Davids, MD, Principal Investigators, Dana-Farber Cancer Institute
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsParticipants in the Phase I portion of the study enrolled in outpatient clinic setting from 11/20/2014 to 12/22/2018 and to the Phase II study from 1/14/2016 to 5/29/2018. The MCL and CLL arms were enrolled independently of each other, and were allowed to begin enrolling to the protocol scheduled expansion independent of the other arm.
    Pre-assignment Detail
    Arm/Group TitleCLL: Phase I Cohort 1MCL: Phase I Cohort 1CLL: Phase I Cohort 2MCL: Phase I Cohort 2CLL: Phase I/II Cohort 3 (RPD2)MCL: Phase I/II Cohort 3 (RPD2)
    Arm/Group DescriptionPhase I Cohort 1 patients received oral agent TGR1202 400mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 1 patients received oral agent TGR1202 400mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 560 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 2 patients received oral agent TGR1202 600mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 2 patients received oral agent TGR1202 600mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 3 patients received oral agent TGR1202 800mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 3 patients received oral agent TGR1202 800mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.
    Period Title: Overall Study
    STARTED33431515
    COMPLETED203084
    NOT COMPLETED1313711

    Baseline Characteristics

    Arm/Group TitleCLL: Phase I Cohort 1MCL: Phase 1 Cohort 1CLL: Phase I Cohort 2MCL: Phase I Cohort 2CLL Phase I/IICohort 3 (RPD2)MCL Phase I/II Cohort 3 (RPD2)Total
    Arm/Group DescriptionPhase I Cohort 1 patients received oral agent TGR1202 400mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 1 patients received oral agent TGR1202 400mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 560 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 2 patients received oral agent TGR1202 600mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 2 patients received oral agent TGR1202 600mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 560 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 3 patients received oral agent TGR1202 800mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 3 patients received oral agent TGR1202 800mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 560 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Total of all reporting groups
    Overall Participants3343151543
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    3
    100%
    1
    33.3%
    2
    50%
    1
    33.3%
    2
    13.3%
    3
    20%
    12
    27.9%
    >=65 years
    0
    0%
    2
    66.7%
    2
    50%
    2
    66.7%
    13
    86.7%
    12
    80%
    31
    72.1%
    Sex: Female, Male (Count of Participants)
    Female
    2
    66.7%
    0
    0%
    3
    75%
    2
    66.7%
    5
    33.3%
    5
    33.3%
    17
    39.5%
    Male
    1
    33.3%
    3
    100%
    1
    25%
    1
    33.3%
    10
    66.7%
    10
    66.7%
    26
    60.5%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    2.3%
    White
    2
    66.7%
    3
    100%
    4
    100%
    2
    66.7%
    15
    100%
    15
    100%
    41
    95.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    1
    2.3%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    3
    100%
    3
    100%
    4
    100%
    3
    100%
    15
    100%
    15
    100%
    43
    100%

    Outcome Measures

    1. Primary Outcome
    TitleNumber of Patients Who Experienced a Dose Limiting Toxicity (DLT) During Phase I
    DescriptionTo assess the safety of TGR1202 in combination with ibrutinib relapsed or refractory CLL or MCL. DLT is based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. DLT refers to toxicities experienced at any time during the study treatment, defined as Grade 4 anemia; Grade 4 neutropenia lasting >7 days (while receiving growth factor support); Grade 4 thrombocytopenia lasting > 7 days; Grade ≥3 febrile neutropenia; and Grade ≥3 thrombocytopenia with Grade >2 hemorrhage;Grade ≥ 3 non-hematologic toxicity unresponsive to standard supportive care measure with the exception of asymptomatic Grade ≥3 lab abnormalities that resolve to ≤ Grade 1 or baseline within 7 days;treatment delay of ≥14 days due to unresolved toxicity; and non-hematologic toxicity of Grade 2 (at any time during treatment) that, in the judgment of the Investigators, Study Chair, and the Medical Monitor, is dose-limiting.
    Time FrameParticipants were assessed every week or more often as needed during Cycle 1 or more often for up to 28 days to assess Dose-limiting toxicities (DLTs) during Phase I

    Outcome Measure Data

    Analysis Population Description
    Patients who have been previously treated for MCL, CLL or SLL. MCL must have 1 measurable site of disease and have had received at least one prior standard therapy; CLL/SLL patients must have an indication for treatment according to 2008 ICWLL criteria and received at least one prior standard treatment regimen
    Arm/Group TitleCLL: Phase I Cohort 1MCL: Phase 1 Cohort 1CLL: Phase I Cohort 2MCL: Phase I Cohort 2CLL Phase I/IICohort 3 (RPD2)MCL Phase I/II Cohort 3 (RPD2)
    Arm/Group DescriptionPhase I Cohort 1 patients received oral agent TGR1202 400mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 1 patients received oral agent TGR1202 400mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 560 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 2 patients received oral agent TGR1202 600mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 2 patients received oral agent TGR1202 600mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 3 patients received oral agent TGR1202 800mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 3 patients received oral agent TGR1202 800mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.
    Measure Participants33331515
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2. Secondary Outcome
    TitleOverall Response Rate
    DescriptionResponse and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008) by Lugano Criteria ( Cheson et al,.24) for MCL
    Time FrameAt baseline, End of Cycle 2, End of Cycle 5, End of Cycle 9, End of Cycle 14 and approximately q6 months until C26, then investigator discretion thereafter

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    3. Secondary Outcome
    TitleRate of Nodal Response With Lymphocytosis (nPR)
    Description
    Time Frame2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    4. Secondary Outcome
    TitleRate of Progression Free Survival
    Description
    Time Frame2 Years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    5. Secondary Outcome
    TitleDuration of Response
    Description
    Time Frame2 Years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time FrameAdverse events are assessed at minimum every week during cycle 1, on days 1 and 15 of cycle 2, every Day 1 of cycles 3-6 where every cycle is 28 days. Cycles 8-12, participants are evaluated every other cycle on Day 1, and then every 3 cycles Cycle 12 onward to Cycle 36, then every 6 cycles on Day 1 thereafter. The DLT period was the first 28 days of treatment during Phase I. AEs were assessed up to 30 days after drug discontinuation.
    Adverse Event Reporting Description Maximum grade toxicity by type-Serious AEs were defined as per DFCI criteria: Any grade 2 or 3 unexpected and treatment related event, unexpected grade 4 events, all grade 5 events regardless of attribution to study treatment. Includes events deemed medically important by overall PI. Other AEs were defined as events with the attribution of at least possibly related to the study treatment that did not meet the SAE criteria. CTCAE 4.0 was used in investigator assessment and lab value review.
    Arm/Group TitleCLL: Phase I Cohort 1MCL: Phase I Cohort 1CLL: Phase I Cohort 2MCL: Phase I Cohort 2CLL: Phase I/IICohort 3 (RPD2)MCL: Phase I/II Cohort 3 (RPD2)
    Arm/Group DescriptionPhase I Cohort 1 patients received oral agent TGR1202 400mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 1 patients received oral agent TGR1202 400mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 560 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 2 patients received oral agent TGR1202 600mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 2 patients received oral agent TGR1202 600mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 3 patients received oral agent TGR1202 800mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.Phase I Cohort 3 patients received oral agent TGR1202 800mg daily on days 1-28 of a 28 day cycle and ibrutinib orally 420 mg daily on days 1-28 of a 28 day cycle. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.
    All Cause Mortality
    CLL: Phase I Cohort 1MCL: Phase I Cohort 1CLL: Phase I Cohort 2MCL: Phase I Cohort 2CLL: Phase I/IICohort 3 (RPD2)MCL: Phase I/II Cohort 3 (RPD2)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/3 (33.3%) 1/3 (33.3%) 0/4 (0%) 1/3 (33.3%) 2/15 (13.3%) 3/15 (20%)
    Serious Adverse Events
    CLL: Phase I Cohort 1MCL: Phase I Cohort 1CLL: Phase I Cohort 2MCL: Phase I Cohort 2CLL: Phase I/IICohort 3 (RPD2)MCL: Phase I/II Cohort 3 (RPD2)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total2/3 (66.7%) 1/3 (33.3%) 0/4 (0%) 1/3 (33.3%) 3/15 (20%) 5/15 (33.3%)
    Cardiac disorders
    Supraventricular Tachycardia1/3 (33.3%) 10/3 (0%) 00/4 (0%) 00/3 (0%) 00/15 (0%) 00/15 (0%) 0
    General disorders
    Sudden Death0/3 (0%) 00/3 (0%) 00/4 (0%) 00/3 (0%) 01/15 (6.7%) 11/15 (6.7%) 1
    Infections and infestations
    Sepsis1/3 (33.3%) 10/3 (0%) 00/4 (0%) 00/3 (0%) 00/15 (0%) 00/15 (0%) 0
    Paraspinal Infection0/3 (0%) 00/3 (0%) 00/4 (0%) 00/3 (0%) 00/15 (0%) 01/15 (6.7%) 1
    Fungal Pneumonia0/3 (0%) 00/3 (0%) 00/4 (0%) 00/3 (0%) 00/15 (0%) 01/15 (6.7%) 1
    Cellulitis0/3 (0%) 00/3 (0%) 00/4 (0%) 00/3 (0%) 00/15 (0%) 01/15 (6.7%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Disease Progression1/3 (33.3%) 11/3 (33.3%) 10/4 (0%) 01/3 (33.3%) 12/15 (13.3%) 22/15 (13.3%) 2
    Other (Not Including Serious) Adverse Events
    CLL: Phase I Cohort 1MCL: Phase I Cohort 1CLL: Phase I Cohort 2MCL: Phase I Cohort 2CLL: Phase I/IICohort 3 (RPD2)MCL: Phase I/II Cohort 3 (RPD2)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/3 (100%) 3/3 (100%) 4/4 (100%) 3/3 (100%) 15/15 (100%) 15/15 (100%)
    Blood and lymphatic system disorders
    Anemia2/3 (66.7%) 3/3 (100%) 3/4 (75%) 2/3 (66.7%) 15/15 (100%) 7/15 (46.7%)
    Leukocytosis2/3 (66.7%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 5/15 (33.3%) 0/15 (0%)
    Cardiac disorders
    Atrial fibrillation0/3 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 3/15 (20%) 1/15 (6.7%)
    Ear and labyrinth disorders
    Hearing impaired1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 2/15 (13.3%) 1/15 (6.7%)
    Eye disorders
    Blurred vision1/3 (33.3%) 0/3 (0%) 1/4 (25%) 1/3 (33.3%) 3/15 (20%) 1/15 (6.7%)
    Gastrointestinal disorders
    Abdominal pain1/3 (33.3%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 1/15 (6.7%) 2/15 (13.3%)
    Bloating0/3 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 1/15 (6.7%) 2/15 (13.3%)
    Colitis1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/15 (0%) 2/15 (13.3%)
    Constipation1/3 (33.3%) 0/3 (0%) 1/4 (25%) 1/3 (33.3%) 4/15 (26.7%) 4/15 (26.7%)
    Diarrhea2/3 (66.7%) 3/3 (100%) 2/4 (50%) 3/3 (100%) 10/15 (66.7%) 12/15 (80%)
    Dyspepsia1/3 (33.3%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 1/15 (6.7%) 2/15 (13.3%)
    Flatulence0/3 (0%) 0/3 (0%) 1/4 (25%) 1/3 (33.3%) 0/15 (0%) 1/15 (6.7%)
    Gastroesophageal reflux disease0/3 (0%) 1/3 (33.3%) 0/4 (0%) 3/3 (100%) 2/15 (13.3%) 5/15 (33.3%)
    Gastrointestinal disorders - Other, specify0/3 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 1/15 (6.7%) 3/15 (20%)
    Lip pain0/3 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 2/15 (13.3%) 1/15 (6.7%)
    Mucositis oral1/3 (33.3%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 1/15 (6.7%) 2/15 (13.3%)
    Nausea1/3 (33.3%) 0/3 (0%) 1/4 (25%) 2/3 (66.7%) 8/15 (53.3%) 9/15 (60%)
    Oral pain0/3 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 1/15 (6.7%) 1/15 (6.7%)
    Stomach pain1/3 (33.3%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 2/15 (13.3%) 0/15 (0%)
    Toothache0/3 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Vomiting1/3 (33.3%) 0/3 (0%) 1/4 (25%) 1/3 (33.3%) 2/15 (13.3%) 5/15 (33.3%)
    General disorders
    Edema limbs2/3 (66.7%) 0/3 (0%) 2/4 (50%) 1/3 (33.3%) 3/15 (20%) 3/15 (20%)
    Fatigue3/3 (100%) 2/3 (66.7%) 3/4 (75%) 3/3 (100%) 12/15 (80%) 13/15 (86.7%)
    Fever1/3 (33.3%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 1/15 (6.7%) 2/15 (13.3%)
    Localized edema2/3 (66.7%) 0/3 (0%) 1/4 (25%) 1/3 (33.3%) 1/15 (6.7%) 3/15 (20%)
    Malaise0/3 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 2/15 (13.3%) 1/15 (6.7%)
    Non-cardiac chest pain1/3 (33.3%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Pain0/3 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 3/15 (20%) 0/15 (0%)
    Infections and infestations
    Infections and infestations - Other, specify0/3 (0%) 0/3 (0%) 3/4 (75%) 0/3 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Lung infection0/3 (0%) 0/3 (0%) 2/4 (50%) 0/3 (0%) 5/15 (33.3%) 4/15 (26.7%)
    Nail infection0/3 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 1/15 (6.7%) 2/15 (13.3%)
    Sinusitis0/3 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 2/15 (13.3%) 0/15 (0%)
    Skin infection1/3 (33.3%) 0/3 (0%) 2/4 (50%) 0/3 (0%) 2/15 (13.3%) 2/15 (13.3%)
    Upper respiratory infection3/3 (100%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 6/15 (40%) 1/15 (6.7%)
    Urinary tract infection1/3 (33.3%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 2/15 (13.3%) 0/15 (0%)
    Injury, poisoning and procedural complications
    Bruising1/3 (33.3%) 2/3 (66.7%) 1/4 (25%) 0/3 (0%) 9/15 (60%) 7/15 (46.7%)
    Fall0/3 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 3/15 (20%) 2/15 (13.3%)
    Investigations
    Alanine aminotransferase increased1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 2/15 (13.3%) 3/15 (20%)
    Alkaline phosphatase increased2/3 (66.7%) 1/3 (33.3%) 3/4 (75%) 1/3 (33.3%) 1/15 (6.7%) 2/15 (13.3%)
    Aspartate aminotransferase increased3/3 (100%) 2/3 (66.7%) 1/4 (25%) 2/3 (66.7%) 7/15 (46.7%) 5/15 (33.3%)
    Blood bilirubin increased1/3 (33.3%) 0/3 (0%) 2/4 (50%) 1/3 (33.3%) 3/15 (20%) 4/15 (26.7%)
    Creatinine increased1/3 (33.3%) 1/3 (33.3%) 1/4 (25%) 1/3 (33.3%) 5/15 (33.3%) 3/15 (20%)
    Lipase increased0/3 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Lymphocyte count decreased0/3 (0%) 1/3 (33.3%) 2/4 (50%) 1/3 (33.3%) 1/15 (6.7%) 6/15 (40%)
    Lymphocyte count increased3/3 (100%) 2/3 (66.7%) 2/4 (50%) 0/3 (0%) 11/15 (73.3%) 2/15 (13.3%)
    Neutrophil count decreased1/3 (33.3%) 3/3 (100%) 2/4 (50%) 0/3 (0%) 13/15 (86.7%) 7/15 (46.7%)
    Platelet count decreased2/3 (66.7%) 3/3 (100%) 2/4 (50%) 2/3 (66.7%) 15/15 (100%) 10/15 (66.7%)
    Weight gain0/3 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 4/15 (26.7%) 2/15 (13.3%)
    Weight loss0/3 (0%) 1/3 (33.3%) 2/4 (50%) 0/3 (0%) 0/15 (0%) 2/15 (13.3%)
    White blood cell decreased2/3 (66.7%) 2/3 (66.7%) 2/4 (50%) 0/3 (0%) 4/15 (26.7%) 7/15 (46.7%)
    Metabolism and nutrition disorders
    Anorexia0/3 (0%) 0/3 (0%) 0/4 (0%) 3/3 (100%) 4/15 (26.7%) 2/15 (13.3%)
    Dehydration2/3 (66.7%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Hyperglycemia3/3 (100%) 1/3 (33.3%) 2/4 (50%) 3/3 (100%) 14/15 (93.3%) 7/15 (46.7%)
    Hyperkalemia0/3 (0%) 1/3 (33.3%) 1/4 (25%) 1/3 (33.3%) 1/15 (6.7%) 3/15 (20%)
    Hyperuricemia0/3 (0%) 1/3 (33.3%) 0/4 (0%) 1/3 (33.3%) 3/15 (20%) 2/15 (13.3%)
    Hypoalbuminemia1/3 (33.3%) 1/3 (33.3%) 2/4 (50%) 3/3 (100%) 4/15 (26.7%) 4/15 (26.7%)
    Hypocalcemia1/3 (33.3%) 2/3 (66.7%) 2/4 (50%) 2/3 (66.7%) 7/15 (46.7%) 5/15 (33.3%)
    Hypoglycemia0/3 (0%) 2/3 (66.7%) 0/4 (0%) 2/3 (66.7%) 6/15 (40%) 4/15 (26.7%)
    Hypokalemia0/3 (0%) 1/3 (33.3%) 2/4 (50%) 0/3 (0%) 3/15 (20%) 8/15 (53.3%)
    Hypomagnesemia1/3 (33.3%) 1/3 (33.3%) 0/4 (0%) 1/3 (33.3%) 2/15 (13.3%) 6/15 (40%)
    Hyponatremia1/3 (33.3%) 1/3 (33.3%) 3/4 (75%) 3/3 (100%) 5/15 (33.3%) 6/15 (40%)
    Hypophosphatemia2/3 (66.7%) 1/3 (33.3%) 1/4 (25%) 1/3 (33.3%) 3/15 (20%) 6/15 (40%)
    Musculoskeletal and connective tissue disorders
    Arthralgia2/3 (66.7%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 3/15 (20%) 1/15 (6.7%)
    Arthritis1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 2/15 (13.3%) 0/15 (0%)
    Back pain3/3 (100%) 0/3 (0%) 1/4 (25%) 1/3 (33.3%) 5/15 (33.3%) 3/15 (20%)
    Generalized muscle weakness0/3 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 2/15 (13.3%) 2/15 (13.3%)
    Musculoskeletal and connective tissue disorder - Other, specify0/3 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 1/15 (6.7%) 2/15 (13.3%)
    Myalgia2/3 (66.7%) 2/3 (66.7%) 1/4 (25%) 0/3 (0%) 4/15 (26.7%) 2/15 (13.3%)
    Pain in extremity2/3 (66.7%) 0/3 (0%) 3/4 (75%) 1/3 (33.3%) 2/15 (13.3%) 2/15 (13.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify1/3 (33.3%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/15 (0%) 3/15 (20%)
    Nervous system disorders
    Dizziness2/3 (66.7%) 1/3 (33.3%) 2/4 (50%) 2/3 (66.7%) 6/15 (40%) 4/15 (26.7%)
    Dysgeusia0/3 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 2/15 (13.3%) 1/15 (6.7%)
    Headache2/3 (66.7%) 2/3 (66.7%) 2/4 (50%) 1/3 (33.3%) 4/15 (26.7%) 6/15 (40%)
    Memory impairment0/3 (0%) 0/3 (0%) 1/4 (25%) 1/3 (33.3%) 1/15 (6.7%) 2/15 (13.3%)
    Nervous system disorders - Other, specify1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 2/15 (13.3%) 0/15 (0%)
    Paresthesia0/3 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 1/15 (6.7%) 1/15 (6.7%)
    Peripheral sensory neuropathy0/3 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 1/15 (6.7%) 1/15 (6.7%)
    Tremor0/3 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/15 (0%) 2/15 (13.3%)
    Psychiatric disorders
    Anxiety1/3 (33.3%) 0/3 (0%) 1/4 (25%) 1/3 (33.3%) 0/15 (0%) 3/15 (20%)
    Confusion0/3 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 2/15 (13.3%) 4/15 (26.7%)
    Insomnia2/3 (66.7%) 0/3 (0%) 1/4 (25%) 1/3 (33.3%) 3/15 (20%) 4/15 (26.7%)
    Renal and urinary disorders
    Urinary frequency0/3 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 3/15 (20%) 1/15 (6.7%)
    Reproductive system and breast disorders
    Reproductive system and breast disorders - Other, specify1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/15 (0%) 2/15 (13.3%)
    Respiratory, thoracic and mediastinal disorders
    Cough1/3 (33.3%) 1/3 (33.3%) 2/4 (50%) 1/3 (33.3%) 7/15 (46.7%) 3/15 (20%)
    Dyspnea0/3 (0%) 1/3 (33.3%) 2/4 (50%) 0/3 (0%) 5/15 (33.3%) 4/15 (26.7%)
    Epistaxis1/3 (33.3%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 2/15 (13.3%) 0/15 (0%)
    Nasal congestion2/3 (66.7%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 3/15 (20%) 3/15 (20%)
    Sore throat0/3 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Skin and subcutaneous tissue disorders
    Alopecia1/3 (33.3%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 1/15 (6.7%) 0/15 (0%)
    Dry skin0/3 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 1/15 (6.7%) 2/15 (13.3%)
    Hyperhidrosis3/3 (100%) 0/3 (0%) 2/4 (50%) 1/3 (33.3%) 3/15 (20%) 1/15 (6.7%)
    Nail loss0/3 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 3/15 (20%) 1/15 (6.7%)
    Pruritus0/3 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 2/15 (13.3%) 2/15 (13.3%)
    Rash acneiform0/3 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 1/15 (6.7%) 2/15 (13.3%)
    Rash maculo-papular0/3 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 6/15 (40%) 3/15 (20%)
    Skin/subcutaneous tissue disorders1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Vascular disorders
    Hematoma1/3 (33.3%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 4/15 (26.7%) 0/15 (0%)
    Hypertension0/3 (0%) 0/3 (0%) 2/4 (50%) 1/3 (33.3%) 3/15 (20%) 5/15 (33.3%)
    Hypotension0/3 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Thromboembolic event1/3 (33.3%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 1/15 (6.7%) 0/15 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT 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/TitleMatthew Davids, MD, MMSc
    OrganizationDana-Farber Cancer Institute
    Phone617-632-6331
    Emailmatthew_davids@dfci.harvard.edu
    Responsible Party:
    Matthew S. Davids, MD, Principal Investigators, Dana-Farber Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT02268851
    Other Study ID Numbers:
    • 14-396
    • TGR-IB-105
    First Posted:
    Oct 20, 2014
    Last Update Posted:
    Oct 4, 2021
    Last Verified:
    Sep 1, 2021