UC-961 (Cirmtuzumab) in Relapsed or Refractory Chronic Lymphocytic Leukemia

Sponsor
Thomas Kipps (Other)
Overall Status
Completed
CT.gov ID
NCT02222688
Collaborator
(none)
26
1
7
44.7
0.6

Study Details

Study Description

Brief Summary

The purpose of the study is to investigate the safety of the investigational agent, cirmtuzumab. Cirmtuzumab is a monoclonal antibody drug designed to attach to a protein, called ROR1, on the surface of chronic lymphocytic leukemia (CLL) cells to block cell growth and survival. ROR1 is rarely expressed on healthy cells so the idea is to preferentially get rid of the cancer cells. Although there is evidence in laboratory animals that cirmtuzumab can decrease the number of CLL cells, the investigators do not know if this will work in humans. This drug will be given to humans for the first time in this study. Therefore, the goal of this study is to see if cirmtuzumab is safe and tolerated in study participants.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

This is a first in human, open-label single institution, Phase I dose escalation study of in patients with relapsed or refractory CLL. Treatment cycle (14 days) will consist of cirmtuzumab administered intravenously on a bi-weekly (every two weeks) schedule for a total of 4 doses. Eight dose cohorts (of 3 to 6 patients in size) plus an expansion cohort of 6 patients are planned. In the first 4 dose cohorts, there is intra-patient dose escalation to monitor for acute toxicities, such as tumor lysis syndrome.

A cycle may be repeated every 14 days if the patient has at least stable disease by clinical examination (or interim response assessment) and has again met hematologic, renal, and hepatic laboratory parameters as defined in the eligibility section, and is without ongoing Grade 3 non-hematologic or Grade 4 hematologic toxicities attributable to cirmtuzumab. The total duration of study drug administration is 4 cycles. Each cycle consists of clinical and laboratory evaluation on Day 1 and safety assessments on Days 3 and 8.

Study Design

Study Type:
Interventional
Actual Enrollment :
26 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Clinical Trial to Determine the Safety and Tolerability of UC-961 (Cirmtuzumab), an Anti-ROR1 Monoclonal Antibody, for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia Who Are Ineligible for Chemotherapy
Actual Study Start Date :
Aug 8, 2014
Actual Primary Completion Date :
Oct 10, 2017
Actual Study Completion Date :
May 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cirmtuzumab 0.015 - 0.03 mg/kg

Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion

Drug: cirmtuzumab
Other Names:
  • UC-961
  • Experimental: Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg

    Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion

    Drug: cirmtuzumab
    Other Names:
  • UC-961
  • Experimental: Cirmtuzumab 0.5 - 1.0 mg/kg

    Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion

    Drug: cirmtuzumab
    Other Names:
  • UC-961
  • Experimental: Cirmtuzumab 2.0 - 4.0 mg/kg

    Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion

    Drug: cirmtuzumab
    Other Names:
  • UC-961
  • Experimental: Cirmtuzumab 8 mg/kg

    Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion

    Drug: cirmtuzumab
    Other Names:
  • UC-961
  • Experimental: Cirmtuzumab 16 mg/kg

    Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion

    Drug: cirmtuzumab
    Other Names:
  • UC-961
  • Experimental: Cirmtuzumab 20 mg/kg

    Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)

    Drug: cirmtuzumab
    Other Names:
  • UC-961
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) or Biologically Active Dose of Cirmtuzumab [1 year]

      The MTD is defined as the highest dose studied at which no more than one in six patients experience a dose-limiting toxicity (DLT) during the DLT observation period. The biologically active dose will be determined at a dose below or equal to the MTD upon review of the the study data; the final determination will also consider any cumulative or delayed toxicity.

    2. Rate of Dose Limiting Toxicities (DLTs) [The DLT observation period is 56 days from the start of the first infusion for the intra-patient dosing cohorts and 28 days after the start of the first infusion for subsequent dosing cohorts]

      The occurrence of any of the following adverse events considered to be possibly, probably, or definitely related to cirmtuzumab within the DLT observation period (56 days from the first infusion for cohorts with intrapatient dose escalation, and 28 days of the start investigational treatment for cohorts without intrapatient dose escalation): Grade 3 or greater non-hematologic toxicity with the exception of Grade 3 infusion reaction. Grade 4 neutropenia lasting more than 5 days despite appropriate medical management. Grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding or any requirement for platelets transfusion. Grade 3 or greater febrile neutropenia (temperature ≥ 38.5ºC). Grade 4 anemia unexplained by underlying disease. Any AE requiring a dose delay of greater than 14 days. Patients with baseline cytopenias or starting blood counts in the grade 2 range are evaluable for hematologic DLT.

    Secondary Outcome Measures

    1. Safety and Tolerability of UC-961 by Ongoing Evaluation of AEs. [From the start of investigational treatment to completion of follow-up, an average of 33 weeks]

      Treatment emergent adverse events (description, timing, CTCAE grade, severity, seriousness, and relatedness)

    2. Clinical Activity Determined by the International Working Group in CLL (iwCLL) Criteria [From baseline visit to response assessment visit at 56 days after final cirmtuzumab infusion, an average of 52 days]

      Clinical response [stable disease (SD) or progressive disease (PD)] defined by iwCLL criteria including clinical, hematological, and bone marrow features for a period of at least 2 months from completion of therapy

    3. Progression Free Survival as Determined by iwCLL Criteria [From start of treatment until objective tumor progression or death]

      The duration of time from the start of study treatment until objective tumor progression or death

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    INCLUSION CRITERIA:
    • Clinical and phenotypic verification of B cell CLL and measurable disease. Immunophenotyping of the leukemic cells must demonstrate a monoclonal B cell population with immunophenotype consistent with CLL.

    • Relapsed or refractory disease, defined by failure to achieve a partial response within 6 months of initiation of therapy, or a 50% increase of baseline disease measurements after achieving a clinical response.

    • Not amenable to approved therapies.

    • Prior Therapy: Must have progressed after purine-analog or alkylator based therapy, or be considered inappropriate for chemo-immunotherapy due to one of the following:

    • Del 17p, which is associated with poor response to chemo-immunotherapy, or

    • Age greater than 70, or

    • Age greater than 65 with one of the following:

    • Grade ≥ 3 neutropenia, anemia, or thrombocytopenia attributable to cumulative myelotoxicity from prior administration of cytotoxic agents (as documented by bone marrow biopsy obtained since last prior therapy), or

    • Clinically apparent autoimmune cytopenia which may be exacerbated by fludarabine therapy, or

    • Estimated creatinine clearance (eCCr) <70 mL/min (as determined by the Cockcroft-Gault method), or

    • Eastern Cooperative Oncology Group (ECOG) performance status greater than 0.

    • Has recovered from the toxic effects of prior therapy to their clinical baseline.

    • Women of childbearing potential must agree not to become pregnant for the duration of the study. Both men and women must agree to use a barrier method of contraception for the duration of the study and until 10 weeks after the final dose of cirmtuzumab.

    • Subjects must have at least one of the following indications for treatment:

    • Symptomatic or progressive splenomegaly;

    • Symptomatic lymph nodes, nodal clusters, or progressive lymphadenopathy;

    • Progressive anemia (hemoglobin ≤ 11 g/dL);

    • Progressive thrombocytopenia (platelets ≤ 100 x 10^9/L);

    • Weight loss > 10% body weight over the preceding 6 month period;

    • Fatigue attributable to CLL;

    • Fever or night sweats for > 2 weeks without evidence of infection;

    • Progressive lymphocytosis with an increase of > 50% over a 2-month period or an anticipated doubling time of less than 12 months.

    • Subjects must have an ECOG performance status of 0-2.

    • Adequate hematologic function

    • Adequate renal function

    • Adequate hepatic function

    • Adequate coagulation tests

    EXCLUSION CRITERIA:
    • Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies.

    • Patients who are currently receiving another investigational agent are excluded.

    • Patients who have had chemotherapy (e.g., purine analogues, alkylating agents), immunotherapy, radiation therapy, or participation in any investigational drug treatment within 4 weeks of initiation of UC-961 or at any time during the study.

    • Patients who have had prior (within 8 weeks of initiation of UC-961) or concurrent antibody therapy directed against CLL (i.e., Rituxan® and Campath®).

    • Current infection requiring parenteral antibiotics.

    • Active infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV).

    • Concurrent malignancy or prior malignancy within the previous 3 years (other than completely resected carcinoma in situ, prostate cancer, or localized non-melanoma skin cancer).

    • Known central nervous system (CNS) involvement by malignancy.

    • Untreated autoimmunity such as autoimmune hemolytic anemia, or immune thrombocytopenia.

    • Uncompensated hypothyroidism (defined as thyroid-stimulating hormone (TSH) greater than 2x upper limit of normal not treated with replacement hormone).

    • Presence of more than 55% pro-lymphocytes in peripheral blood. Patients with Richter's transformation are not excluded.

    • Insufficient recovery from surgical-related trauma or wound healing.

    • Impaired cardiac function including any of the following:

    • Myocardial infarction within 6 months of starting study drug;

    • A past medical history of clinically significant ECG abnormalities, including QTc 481 milliseconds or greater;

    • Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCSD Moores Cancer Center La Jolla California United States 92093

    Sponsors and Collaborators

    • Thomas Kipps

    Investigators

    • Principal Investigator: Catriona Jamieson, M.D., Ph.D., University of California Medical Center
    • Principal Investigator: Michael Choi, M.D., University of Calilfornia Medical Center

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Thomas Kipps, Deputy Director of Research Operations, Moores Cancer Center, University of California, San Diego
    ClinicalTrials.gov Identifier:
    NCT02222688
    Other Study ID Numbers:
    • #140141
    First Posted:
    Aug 21, 2014
    Last Update Posted:
    Aug 13, 2020
    Last Verified:
    Jul 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Thomas Kipps, Deputy Director of Research Operations, Moores Cancer Center, University of California, San Diego
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Subjects were enrolled into the study between August 2014 and September 2017 and included patients seen in the UCSD Health system.
    Pre-assignment Detail Twenty-seven subjects were treated with cirmtuzumab and are included in the primary outcome analysis. One subject was enrolled into the trial twice; first in Cohort 1 and then again in Cohort 4 and is counted once for reporting of the baseline characteristics.
    Arm/Group Title Cirmtuzumab 0.015 - 0.03 mg/kg Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg Cirmtuzumab 0.5 - 1.0 mg/kg Cimrtuzumab 2.0 - 4.0 mg/kg Cirmtuzumab 8 mg/kg Cirmtuzumab 16 mg/kg Cirmtuzumab 20 mg/kg
    Arm/Group Description Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)
    Period Title: Overall Study
    STARTED 4 3 3 5 3 3 6
    COMPLETED 3 3 3 3 2 3 5
    NOT COMPLETED 1 0 0 2 1 0 1

    Baseline Characteristics

    Arm/Group Title Cirmtuzumab 0.015 - 0.03 mg/kg Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg Cirmtuzumab 0.5 - 1.0 mg/kg Cirmtuzumab 2.0 - 4.0 mg/kg Cirmtuzumab 8 mg/kg Cirmtuzumab 16 mg/kg Cirmtuzumab 20 mg/kg Total
    Arm/Group Description Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg) Total of all reporting groups
    Overall Participants 4 3 3 5 3 3 6 27
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    0
    0%
    1
    33.3%
    1
    33.3%
    1
    20%
    0
    0%
    1
    33.3%
    1
    16.7%
    5
    18.5%
    >=65 years
    4
    100%
    2
    66.7%
    2
    66.7%
    4
    80%
    3
    100%
    2
    66.7%
    5
    83.3%
    22
    81.5%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    72.75
    (1.5)
    70.67
    (11.68)
    66.67
    (3.51)
    69.4
    (7.23)
    70
    (2.65)
    71.67
    (9.29)
    77.33
    (8.78)
    71.81
    (7.32)
    Sex: Female, Male (Count of Participants)
    Female
    2
    50%
    2
    66.7%
    0
    0%
    3
    60%
    1
    33.3%
    1
    33.3%
    4
    66.7%
    13
    48.1%
    Male
    2
    50%
    1
    33.3%
    3
    100%
    2
    40%
    2
    66.7%
    2
    66.7%
    2
    33.3%
    14
    51.9%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    4
    100%
    3
    100%
    3
    100%
    5
    100%
    3
    100%
    3
    100%
    6
    100%
    27
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    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%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    1
    3.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    4
    100%
    3
    100%
    2
    66.7%
    5
    100%
    3
    100%
    2
    66.7%
    6
    100%
    25
    92.6%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    3.7%
    Region of Enrollment (participants) [Number]
    United States
    4
    100%
    3
    100%
    3
    100%
    5
    100%
    3
    100%
    3
    100%
    6
    100%
    27
    100%

    Outcome Measures

    1. Primary Outcome
    Title Maximum Tolerated Dose (MTD) or Biologically Active Dose of Cirmtuzumab
    Description The MTD is defined as the highest dose studied at which no more than one in six patients experience a dose-limiting toxicity (DLT) during the DLT observation period. The biologically active dose will be determined at a dose below or equal to the MTD upon review of the the study data; the final determination will also consider any cumulative or delayed toxicity.
    Time Frame 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title All Participants
    Arm/Group Description All participants who received any treatment with cirmtuzumab
    Measure Participants 27
    Number [mg/kg]
    20
    2. Primary Outcome
    Title Rate of Dose Limiting Toxicities (DLTs)
    Description The occurrence of any of the following adverse events considered to be possibly, probably, or definitely related to cirmtuzumab within the DLT observation period (56 days from the first infusion for cohorts with intrapatient dose escalation, and 28 days of the start investigational treatment for cohorts without intrapatient dose escalation): Grade 3 or greater non-hematologic toxicity with the exception of Grade 3 infusion reaction. Grade 4 neutropenia lasting more than 5 days despite appropriate medical management. Grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding or any requirement for platelets transfusion. Grade 3 or greater febrile neutropenia (temperature ≥ 38.5ºC). Grade 4 anemia unexplained by underlying disease. Any AE requiring a dose delay of greater than 14 days. Patients with baseline cytopenias or starting blood counts in the grade 2 range are evaluable for hematologic DLT.
    Time Frame The DLT observation period is 56 days from the start of the first infusion for the intra-patient dosing cohorts and 28 days after the start of the first infusion for subsequent dosing cohorts

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cirmtuzumab 0.015 - 0.03 mg/kg Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg Cirmtuzumab 0.5 - 1.0 mg/kg Cirmtuzumab 2.0 - 4.0 mg/kg Cirmtuzumab 8 mg/kg Cirmtuzumab 16 mg/kg Cirmtuzumab 20 mg/kg
    Arm/Group Description Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)
    Measure Participants 4 3 3 5 3 3 6
    Number [Occurrence of DLTs]
    0
    0
    0
    0
    0
    0
    0
    3. Secondary Outcome
    Title Safety and Tolerability of UC-961 by Ongoing Evaluation of AEs.
    Description Treatment emergent adverse events (description, timing, CTCAE grade, severity, seriousness, and relatedness)
    Time Frame From the start of investigational treatment to completion of follow-up, an average of 33 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cirmtuzumab 0.015 - 0.03 mg/kg Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg Cirmtuzumab 0.5 - 1.0 mg/kg Cirmtuzumab 2.0 - 4.0 mg/kg Cirmtuzumab 8 mg/kg Cirmtuzumab 16 mg/kg Cirmtuzumab 20 mg/kg
    Arm/Group Description Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)
    Measure Participants 4 3 3 5 3 3 6
    Number [Treatment emergent AEs]
    20
    37
    15
    31
    17
    34
    46
    4. Secondary Outcome
    Title Clinical Activity Determined by the International Working Group in CLL (iwCLL) Criteria
    Description Clinical response [stable disease (SD) or progressive disease (PD)] defined by iwCLL criteria including clinical, hematological, and bone marrow features for a period of at least 2 months from completion of therapy
    Time Frame From baseline visit to response assessment visit at 56 days after final cirmtuzumab infusion, an average of 52 days

    Outcome Measure Data

    Analysis Population Description
    Evaluable subjects or those who completed 4 cycles of cirmtuzumab
    Arm/Group Title Cirmtuzumab 0.015 - 0.03 mg/kg Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg Cirmtuzumab 0.5 - 1.0 mg/kg Cirmtuzumab 2.0 - 4.0 mg/kg Cirmtuzumab 8 mg/kg Cirmtuzumab 16 mg/kg Cirmtuzumab 20 mg/kg
    Arm/Group Description Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)
    Measure Participants 3 3 3 3 2 3 5
    Stable Disease
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    1
    33.3%
    1
    33.3%
    2
    33.3%
    Progressive Disease
    3
    75%
    3
    100%
    2
    66.7%
    3
    60%
    1
    33.3%
    2
    66.7%
    3
    50%
    5. Secondary Outcome
    Title Progression Free Survival as Determined by iwCLL Criteria
    Description The duration of time from the start of study treatment until objective tumor progression or death
    Time Frame From start of treatment until objective tumor progression or death

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cirmtuzumab 0.015 - 0.03 mg/kg Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg Cirmtuzumab 0.5 - 1.0 mg/kg Cirmtuzumab 2.0 - 4.0 mg/kg Cirmtuzumab 8 mg/kg Cirmtuzumab 16 mg/kg Cirmtuzumab 20 mg/kg
    Arm/Group Description Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion
    Measure Participants 4 3 3 5 3 3 6
    Mean (Full Range) [Weeks]
    29.5
    27.6
    24.5
    36.6
    25.4
    26.2
    19.9

    Adverse Events

    Time Frame Adverse events collected from the start of the first infusion of cirmtuzumab to the last subject's final visit in long-term follow-up (on average 3 years 8 months)
    Adverse Event Reporting Description Note that some patients elected to enroll in extension study (ClinicalTrails.gov record #NCT02860676) and therefor the cut-off date for some may be the date patient was first treated on extension protocol. Timeframe for this result therefore difficult to reconcile as asked to report here. Note no deaths observed during the timeframe of the study observation period.
    Arm/Group Title Cirmtuzumab 0.015 - 0.03 mg/kg Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg Cirmtuzumab 0.5 - 1.0 mg/kg Cimrtuzumab 2.0 - 4.0 mg/kg Cirmtuzumab 8 mg/kg Cirmtuzumab 16 mg/kg Cirmtuzumab 20 mg/kg
    Arm/Group Description Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)
    All Cause Mortality
    Cirmtuzumab 0.015 - 0.03 mg/kg Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg Cirmtuzumab 0.5 - 1.0 mg/kg Cimrtuzumab 2.0 - 4.0 mg/kg Cirmtuzumab 8 mg/kg Cirmtuzumab 16 mg/kg Cirmtuzumab 20 mg/kg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%)
    Serious Adverse Events
    Cirmtuzumab 0.015 - 0.03 mg/kg Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg Cirmtuzumab 0.5 - 1.0 mg/kg Cimrtuzumab 2.0 - 4.0 mg/kg Cirmtuzumab 8 mg/kg Cirmtuzumab 16 mg/kg Cirmtuzumab 20 mg/kg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/5 (0%) 0/3 (0%) 1/3 (33.3%) 2/6 (33.3%)
    Gastrointestinal disorders
    Gastrointestinal disorders 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Lung infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 2
    Skin and subcutaneous tissue disorders
    Skin infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Other (Not Including Serious) Adverse Events
    Cirmtuzumab 0.015 - 0.03 mg/kg Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg Cirmtuzumab 0.5 - 1.0 mg/kg Cimrtuzumab 2.0 - 4.0 mg/kg Cirmtuzumab 8 mg/kg Cirmtuzumab 16 mg/kg Cirmtuzumab 20 mg/kg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/4 (100%) 3/3 (100%) 3/3 (100%) 5/5 (100%) 3/3 (100%) 3/3 (100%) 6/6 (100%)
    Blood and lymphatic system disorders
    Anemia 4/4 (100%) 6 3/3 (100%) 12 3/3 (100%) 9 3/5 (60%) 9 3/3 (100%) 10 3/3 (100%) 14 4/6 (66.7%) 10
    Cardiac disorders
    Atrial fibrillation 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Atrial flutter 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Chest pain - cardiac 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Palpitations 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Sinus bradycardia 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Ear and labyrinth disorders
    Ear and labyrinth disorders - other 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    External ear pain 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Eye disorders
    Conjunctivitis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1
    Eye disorders - other 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Floater 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 3 0/6 (0%) 0
    Bloating 0/4 (0%) 0 1/3 (33.3%) 1 2/3 (66.7%) 2 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Constipation 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 3/6 (50%) 3
    Diarrhea 1/4 (25%) 2 3/3 (100%) 3 0/3 (0%) 0 2/5 (40%) 2 2/3 (66.7%) 2 1/3 (33.3%) 2 1/6 (16.7%) 1
    Dry mouth 0/4 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Dyspepsia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1
    Fecal incontinence 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Gastrointestinal reflux disease 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Gastrointestinal disorders - other 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Nausea 1/4 (25%) 1 1/3 (33.3%) 1 1/3 (33.3%) 1 2/5 (40%) 3 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Vomiting 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    General disorders
    Chills 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Fatigue 2/4 (50%) 2 1/3 (33.3%) 1 0/3 (0%) 0 1/5 (20%) 1 1/3 (33.3%) 1 0/3 (0%) 0 2/6 (33.3%) 2
    Fever 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 3 0/6 (0%) 0
    Flu-like symptoms 0/4 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Non-cardiac chest pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Infections and infestations
    Bronchial infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Lung infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 2
    Mucosal infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Papulopustular rash 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Sepsis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Sinusitis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Skin infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 1/6 (16.7%) 1
    Upper respiratory infection 0/4 (0%) 0 1/3 (33.3%) 1 2/3 (66.7%) 2 0/5 (0%) 0 1/3 (33.3%) 2 1/3 (33.3%) 1 2/6 (33.3%) 2
    Urinary tract infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 2
    Injury, poisoning and procedural complications
    Bruising 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Investigations
    Alanine aminotransferase increased 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Aspartate aminotransferase increased 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Blood bilirubin increased 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Creatinine increased 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/5 (20%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Lipase increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 3 0/3 (0%) 0 3/3 (100%) 6 1/6 (16.7%) 1
    Serum amylase increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 2 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Weight loss 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Thrombocytopenia 4/4 (100%) 13 2/3 (66.7%) 9 2/3 (66.7%) 4 4/5 (80%) 8 3/3 (100%) 5 2/3 (66.7%) 7 1/6 (16.7%) 11
    Neutropenia 1/4 (25%) 4 2/3 (66.7%) 7 2/3 (66.7%) 4 2/5 (40%) 2 2/3 (66.7%) 3 2/3 (66.7%) 10 1/6 (16.7%) 3
    Metabolism and nutrition disorders
    Anorexia 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Hyperglycemia 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Hyperkalemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Hypernatremia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hyperuricemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 3 2/6 (33.3%) 3
    Hypokalemia 0/4 (0%) 0 1/3 (33.3%) 3 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Arthritis 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Myalgia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 2
    Pain in extremity 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Nervous system disorders
    Akathisia 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Dizziness 2/4 (50%) 2 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Headache 1/4 (25%) 1 1/3 (33.3%) 3 0/3 (0%) 0 2/5 (40%) 2 0/3 (0%) 0 1/3 (33.3%) 1 2/6 (33.3%) 3
    Parasthesia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Sinus pain 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Transient ischemic attacks 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Psychiatric disorders
    Confusion 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Depression 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Insomnia 2/4 (50%) 2 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Restlessness 0/4 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Renal and urinary disorders
    Cystitis noninfective 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Urinary frequency 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 1/6 (16.7%) 1
    Urinary urgency 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 2
    Urine discoloration 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Reproductive system and breast disorders
    Breast pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Cough 0/4 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 1/5 (20%) 1 1/3 (33.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1
    Dyspnea 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 3/6 (50%) 3
    Epistaxis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 2 0/6 (0%) 0
    Hoarseness 1/4 (25%) 3 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Nasal congestion 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1
    Productive cough 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 1
    Skin and subcutaneous tissue disorders
    Hyperhidrosis 0/4 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Rash maculo-papular 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 1/6 (16.7%) 1
    Skin induration 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Vascular disorders
    Flushing 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hot flashes 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0

    Limitations/Caveats

    Some patients enrolled in extension study (#NCT02860676)& cut-off date for AE observation may be date patient was first treated on extension, therefor AE Timeframe period difficult to reconcile. 0 deaths observed during study observation period.

    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/Title Thomas Kipps, MD, PhD
    Organization University of California, San Diego
    Phone 858-534-5400
    Email tkipps@ucsd.edu
    Responsible Party:
    Thomas Kipps, Deputy Director of Research Operations, Moores Cancer Center, University of California, San Diego
    ClinicalTrials.gov Identifier:
    NCT02222688
    Other Study ID Numbers:
    • #140141
    First Posted:
    Aug 21, 2014
    Last Update Posted:
    Aug 13, 2020
    Last Verified:
    Jul 1, 2020