Ofatumumab and Dinaciclib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-Cell Prolymphocytic Leukemia

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT01515176
Collaborator
(none)
36
1
1
54.6
0.7

Study Details

Study Description

Brief Summary

This phase I/II trial studies the side effects and the best dose of ofatumumab and dinaciclib and to see how well they work in treating patients with relapsed or refractory chronic lymphocytic leukemia, small lymphocytic lymphoma, or B-cell prolymphocytic leukemia. Monoclonal antibodies, such as ofatumumab, can find cancer cells and help kill them. Dinaciclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving ofatumumab together with dinaciclib may kill more cancer cells.

Condition or Disease Intervention/Treatment Phase
  • Drug: Dinaciclib
  • Other: Laboratory Biomarker Analysis
  • Biological: Ofatumumab
  • Other: Pharmacological Study
Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To determine the tolerable dose of combination therapy with ofatumumab and dinaciclib (phase 1b component) in chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), and B-cell prolymphocytic leukemia (B-PLL).

  2. To characterize the toxicity of combination therapy with ofatumumab and dinaciclib in CLL/SLL/B-PLL.

  3. To determine the overall response rate associated with this treatment as assessed by consensus response criteria. (Phase II)

SECONDARY OBJECTIVES:
  1. To estimate progression-free survival (PFS) after combination treatment with ofatumumab and dinaciclib.

  2. To characterize the pharmacokinetics of dinaciclib when given in combination with ofatumumab.

  3. To correlate pharmacokinetic features of dinaciclib with response, toxicity (particularly tumor lysis syndrome), and pharmacodynamic endpoints.

  4. To perform detailed baseline and serial pharmacodynamic studies of combination therapy with ofatumumab and dinaciclib and correlate these with response to therapy.

  5. To correlate baseline disease-risk parameters (i.e., zeta-chain-associated protein kinase [ZAP]-70 expression, interphase cytogenetics, immunoglobulin heavy chain variable region [IgVH] mutational analysis, and other clinical prognostic factors) with response to therapy.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive ofatumumab intravenously (IV) over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib IV over 2 hours on days 2, 8, and 15 of course 2, and on days 1, 8, and 15 of courses 3-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for up to 3 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
36 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1b/2 Study of Dinaciclib (SCH 727965) and Ofatumumab in Relapsed and Refractory CLL/SLL/B-PLL
Actual Study Start Date :
Jan 1, 2012
Actual Primary Completion Date :
Mar 4, 2015
Actual Study Completion Date :
Jul 19, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (ofatumumab, dinaciclib)

Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib IV over 2 hours on days 2, 8, and 15 of course 2, and on days 1, 8, and 15 of courses 3-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.

Drug: Dinaciclib
Given IV
Other Names:
  • CDK Inhibitor SCH 727965
  • MK-7965
  • SCH 727965
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Biological: Ofatumumab
    Given IV
    Other Names:
  • Arzerra
  • GSK1841157
  • HuMax-CD20
  • HuMax-CD20, 2F2
  • Other: Pharmacological Study
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Maximum-tolerated Dose of Dinaciclib When Given in Combination With Ofatumumab, Defined as a Dose Level Where at Most One of 6 Evaluable Patients Has a Dose Limiting Toxicity (Phase Ia) [Day 56]

      Graded according to the National Cancer Institute (NCI) CTCAE version (v)4.0. Assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization.

    2. Number of Patients With Dose-limiting Toxicity Incidents Graded According to the NCI CTCAE v4.0 (Phase I) [Up to day 56]

      Hematologic dose-limiting toxicity measures will be assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via CTCAE version 4 standard toxicity grading. Non-hematologic dose-limiting toxicities such as dyspnea and renal will be evaluated via the ordinal CTCAE standard toxicity grading only.

    3. Percentage of Patients Who Achieve an Overall Response, Defined as Achieving a Complete Response, an Unconfirmed Complete Response (SLL Only), or a Partial Response (Phase II) [Up to 28 weeks]

      Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Secondary Outcome Measures

    1. Complete Response Rate [Up to 28 weeks]

      Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions

    2. Overall Survival [Time from study entry to death due to any cause, assessed up to 5 years]

      Distributions will be explored and assessed using the methods of Kaplan and Meier.

    3. Progression Free Survival [Time from study entry to documentation of disease progression and/or death, assessed up to 5 years]

      95% confidence intervals will be constructed using the methods of Duffy and Santner with the assumption that these rates are binomially distributed. Distributions will be explored and assessed using the methods of Kaplan and Meier.

    4. Time to Treatment Failure [Time from study entry to the date patients end treatment, up to 28 weeks]

      Distributions will be explored and assessed using the methods of Kaplan and Meier.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients must have histologically confirmed B-cell chronic lymphocytic leukemia (B-CLL)/small lymphocytic lymphoma (SLL) or a B-cell prolymphocytic leukemia (B-PLL) according to 2008 World Health Organization (WHO) diagnostic criteria

    • Patients must meet one or more of the following modified indications for treatment as described in the 2008 International Workshop on chronic lymphocytic leukemia (CLL) (IWCLL) guidelines for the diagnosis and treatment of CLL:

    • Progressive disease or marked splenomegaly and/or lymphadenopathy or disease requiring de-bulking for future allogeneic transplantation

    • Anemia (hemoglobin < 11 mg/dL) or thrombocytopenia (platelets < 100,000/μL)

    • Unexplained weight loss exceeding 10% of body weight over the preceding 6 months

    • Cancer Therapy Evaluation Program (CTEP) active version of the Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or 3 fatigue

    • Fevers > 100.5 º F or night sweats for greater than 2 weeks without evidence of infection

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

    • Need for cytoreduction prior to allogeneic stem cell transplant

    • Patients must have received at least one prior therapy that includes either fludarabine or equivalent nucleoside analogue, or an alternative regimen if there was a contraindication (i.e. autoimmune hemolytic anemia) or patient elected not to receive fludarabine

    • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

    • Life expectancy >= 12 weeks

    • Absolute neutrophil count >= 1,000/μL in absence of bone marrow involvement

    • Platelets >= 30,000/μL in absence of bone marrow involvement

    • Total bilirubin =< 1.5 X institutional upper limit of normal (ULN) unless secondary to Gilbert's

    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal (ULN) unless due to infiltration of the liver

    • Creatinine =< 2.0 mg/dL OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients(Cockcroft-Gault estimated)

    • Patients with a history of current/previous infection with hepatitis B virus will be eligible if receiving appropriate antiviral prophylaxis

    • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

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

    Exclusion Criteria:
    • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; corticosteroids alone will not be considered prior therapy, but must be discontinued at least 24 hours prior to the first day of therapy unless continued for indications other than the primary malignancy

    • Patients who are receiving any other investigational agents

    • Patients who have received prior treatment with dinaciclib will not be eligible; patients previously treated with ofatumumab will be eligible as long as their disease responded to previous treatment (defined as achieving at least stable disease by consensus criteria) and did not subsequently progress < 3 months from completing treatment

    • Patients with known brain metastases should be excluded from this clinical trial

    • History of allergic reactions attributed to compounds of similar chemical or biologic composition as dinaciclib

    • History of anaphylactic reaction to rituximab or other anti-cluster of differentiation (CD)20 monoclonal antibody

    • Because dinaciclib is metabolized by the cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) liver enzyme, the eligibility of patients taking medications that are potent inducers or inhibitors of that enzyme will be determined following a review of their case by the principal investigator; every effort should be made to switch patients taking such agents or substances to other medications; any identified agent needs to be stopped at least 2 weeks prior to study registration; use of aprepitant will be permitted, however, based on drug-drug interaction study performed by the manufacturer showing no effect on dinaciclib pharmacokinetics (PK)

    • Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are excluded

    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

    • Pregnant and/or breast-feeding women are excluded from this study; breastfeeding should be discontinued if the mother is treated with dinaciclib

    • Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject is considered by his or her physician to have a 2 year survival expectation

    • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Kerry Rogers, MD, Ohio State University Comprehensive Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01515176
    Other Study ID Numbers:
    • NCI-2012-00101
    • NCI-2012-00101
    • OSU-11120
    • OSU11120
    • CDR0000721353
    • OSU 11120
    • 9031
    • N01CM00070
    • N01CM62207
    • P30CA016058
    • P50CA140158
    • U01CA076576
    • UM1CA186712
    First Posted:
    Jan 23, 2012
    Last Update Posted:
    Mar 15, 2018
    Last Verified:
    Feb 1, 2018

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Dose Level I: Treatment (Ofatumumab, Dinaciclib) Dose Level II: Treatment (Ofatumumab, Dinaciclib)
    Arm/Group Description Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib 7 mg/m2 as a 2-hour infusion on cycle 2 day 2, escalated to 10 mg/m2 beginning with cycle 2 day 8 and continuing thereafter. Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib 7 mg/m2 as a 2-hour infusion on cycle 2 day 2, escalated to 10 mg/m2 as a 2-hour infusion on cycle 2 day 8, and to 14 mg/m2 on cycle 2 day 15 and continuing thereafter
    Period Title: Overall Study
    STARTED 4 32
    COMPLETED 4 32
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Dose Level I: Treatment (Ofatumumab, Dinaciclib) Dose Level II: Total
    Arm/Group Description Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib 7 mg/m2 as a 2-hour infusion on cycle 2 day 2, escalated to 10 mg/m2 beginning with cycle 2 day 8 and continuing thereafter. Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib 7 mg/m2 as a 2-hour infusion on cycle 2 day 2, escalated to 10 mg/m2 as a 2-hour infusion on cycle 2 day 8, and to 14 mg/m2 on cycle 2 day 15 and continuing thereafter Total of all reporting groups
    Overall Participants 4 32 36
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    2
    50%
    15
    46.9%
    17
    47.2%
    >=65 years
    2
    50%
    17
    53.1%
    19
    52.8%
    Sex: Female, Male (Count of Participants)
    Female
    2
    50%
    11
    34.4%
    13
    36.1%
    Male
    2
    50%
    21
    65.6%
    23
    63.9%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    4
    100%
    32
    100%
    36
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    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%
    5
    15.6%
    5
    13.9%
    White
    4
    100%
    27
    84.4%
    31
    86.1%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    4
    100%
    32
    100%
    36
    100%

    Outcome Measures

    1. Primary Outcome
    Title Maximum-tolerated Dose of Dinaciclib When Given in Combination With Ofatumumab, Defined as a Dose Level Where at Most One of 6 Evaluable Patients Has a Dose Limiting Toxicity (Phase Ia)
    Description Graded according to the National Cancer Institute (NCI) CTCAE version (v)4.0. Assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization.
    Time Frame Day 56

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Ofatumumab, Dinaciclib)
    Arm/Group Description Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib IV over 2 hours on days 2, 8, and 15 of course 2, and on days 1, 8, and 15 of courses 3-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity. Dinaciclib: Given IV Laboratory Biomarker Analysis: Correlative studies Ofatumumab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 36
    2 hr infusion cycle 2 day 2
    7
    2 hr infusion cycle 2 day 8
    10
    cycle 2 day 8
    14
    2. Primary Outcome
    Title Number of Patients With Dose-limiting Toxicity Incidents Graded According to the NCI CTCAE v4.0 (Phase I)
    Description Hematologic dose-limiting toxicity measures will be assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via CTCAE version 4 standard toxicity grading. Non-hematologic dose-limiting toxicities such as dyspnea and renal will be evaluated via the ordinal CTCAE standard toxicity grading only.
    Time Frame Up to day 56

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Level I: Treatment (Ofatumumab, Dinaciclib) Dose Level II: Treatment (Ofatumumab, Dinaciclib)
    Arm/Group Description Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib 7 mg/m2 as a 2-hour infusion on cycle 2 day 2, escalated to 10 mg/m2 beginning with cycle 2 day 8 and continuing thereafter. Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib 7 mg/m2 as a 2-hour infusion on cycle 2 day 2, escalated to 10 mg/m2 as a 2-hour infusion on cycle 2 day 8, and to 14 mg/m2 on cycle 2 day 15 and continuing thereafter
    Measure Participants 4 32
    Count of Participants [Participants]
    0
    0%
    0
    0%
    3. Primary Outcome
    Title Percentage of Patients Who Achieve an Overall Response, Defined as Achieving a Complete Response, an Unconfirmed Complete Response (SLL Only), or a Partial Response (Phase II)
    Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
    Time Frame Up to 28 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Level I and Dose Level II
    Arm/Group Description Dose Level I: Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Dose Level II: Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib IV over 2 hours on days 2, 8, and 15 of course 2, and on days 1, 8, and 15 of courses 3-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants 36
    Number (95% Confidence Interval) [percentage of patients]
    39
    4. Secondary Outcome
    Title Complete Response Rate
    Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions
    Time Frame Up to 28 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Ofatumumab, Dinaciclib)
    Arm/Group Description Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib IV over 2 hours on days 2, 8, and 15 of course 2, and on days 1, 8, and 15 of courses 3-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity. Dinaciclib: Given IV Laboratory Biomarker Analysis: Correlative studies Ofatumumab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 36
    Number (95% Confidence Interval) [patients with complete response]
    0
    5. Secondary Outcome
    Title Overall Survival
    Description Distributions will be explored and assessed using the methods of Kaplan and Meier.
    Time Frame Time from study entry to death due to any cause, assessed up to 5 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Ofatumumab, Dinaciclib)
    Arm/Group Description Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib IV over 2 hours on days 2, 8, and 15 of course 2, and on days 1, 8, and 15 of courses 3-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity. Dinaciclib: Given IV Laboratory Biomarker Analysis: Correlative studies Ofatumumab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 36
    Median (95% Confidence Interval) [days]
    990
    6. Secondary Outcome
    Title Progression Free Survival
    Description 95% confidence intervals will be constructed using the methods of Duffy and Santner with the assumption that these rates are binomially distributed. Distributions will be explored and assessed using the methods of Kaplan and Meier.
    Time Frame Time from study entry to documentation of disease progression and/or death, assessed up to 5 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Level I and Dose Level II
    Arm/Group Description Dose Level I: Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Dose Level II: Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib IV over 2 hours on days 2, 8, and 15 of course 2, and on days 1, 8, and 15 of courses 3-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants 36
    Median (95% Confidence Interval) [days]
    322
    7. Secondary Outcome
    Title Time to Treatment Failure
    Description Distributions will be explored and assessed using the methods of Kaplan and Meier.
    Time Frame Time from study entry to the date patients end treatment, up to 28 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Ofatumumab, Dinaciclib)
    Arm/Group Description Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib IV over 2 hours on days 2, 8, and 15 of course 2, and on days 1, 8, and 15 of courses 3-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity. Dinaciclib: Given IV Laboratory Biomarker Analysis: Correlative studies Ofatumumab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 36
    Median (95% Confidence Interval) [days]
    248

    Adverse Events

    Time Frame
    Adverse Event Reporting Description All toxicities will be assessed using the CTEP Active Version of the NCI Common Terminology Criteria for Adverse Events (CTCAE).
    Arm/Group Title Dose Level I: Treatment (Ofatumumab, Dinaciclib) Dose Level II: Treatment (Ofatumumab, Dinaciclib)
    Arm/Group Description Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib 7 mg/m2 as a 2-hour infusion on cycle 2 day 2, escalated to 10 mg/m2 beginning with cycle 2 day 8 and continuing thereafter. Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib 7 mg/m2 as a 2-hour infusion on cycle 2 day 2, escalated to 10 mg/m2 as a 2-hour infusion on cycle 2 day 8, and to 14 mg/m2 on cycle 2 day 15 and continuing thereafter
    All Cause Mortality
    Dose Level I: Treatment (Ofatumumab, Dinaciclib) Dose Level II: Treatment (Ofatumumab, Dinaciclib)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 1/32 (3.1%)
    Serious Adverse Events
    Dose Level I: Treatment (Ofatumumab, Dinaciclib) Dose Level II: Treatment (Ofatumumab, Dinaciclib)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/4 (75%) 32/32 (100%)
    Blood and lymphatic system disorders
    FEBRILE NEUTROPENIA 0/4 (0%) 0 1/32 (3.1%) 2
    LEUKOCYTOSIS 1/4 (25%) 1 0/32 (0%) 0
    Cardiac disorders
    HEART FAILURE 0/4 (0%) 0 1/32 (3.1%) 1
    SUPRAVENTRICULAR TACHYCARDIA 0/4 (0%) 0 1/32 (3.1%) 1
    Gastrointestinal disorders
    ABDOMINAL PAIN 0/4 (0%) 0 1/32 (3.1%) 1
    ASCITES 0/4 (0%) 0 1/32 (3.1%) 1
    General disorders
    DEATH NOS 0/4 (0%) 0 1/32 (3.1%) 1
    FATIGUE 0/4 (0%) 0 2/32 (6.3%) 3
    Infections and infestations
    CATHETER RELATED INFECTION 0/4 (0%) 0 1/32 (3.1%) 1
    HEPATITIS VIRAL 0/4 (0%) 0 1/32 (3.1%) 1
    LUNG INFECTION 0/4 (0%) 0 4/32 (12.5%) 5
    PLEURAL INFECTION 1/4 (25%) 1 0/32 (0%) 0
    SEPSIS 0/4 (0%) 0 3/32 (9.4%) 3
    Investigations
    ALKALINE PHOSPHATASE INCREASED 0/4 (0%) 0 1/32 (3.1%) 2
    EJECTION FRACTION DECREASED 0/4 (0%) 0 1/32 (3.1%) 1
    LYMPHOCYTE COUNT DECREASED 1/4 (25%) 1 0/32 (0%) 0
    Metabolism and nutrition disorders
    HYPERCALCEMIA 0/4 (0%) 0 1/32 (3.1%) 1
    HYPERKALEMIA 0/4 (0%) 0 1/32 (3.1%) 1
    HYPOKALEMIA 0/4 (0%) 0 1/32 (3.1%) 1
    HYPOMAGNESEMIA 0/4 (0%) 0 1/32 (3.1%) 1
    HYPOPHOSPHATEMIA 0/4 (0%) 0 12/32 (37.5%) 14
    TUMOR LYSIS SYNDROME 0/4 (0%) 0 1/32 (3.1%) 1
    Musculoskeletal and connective tissue disorders
    ARTHRITIS 0/4 (0%) 0 1/32 (3.1%) 1
    Respiratory, thoracic and mediastinal disorders
    ATELECTASIS 0/4 (0%) 0 1/32 (3.1%) 1
    DYSPNEA 0/4 (0%) 0 1/32 (3.1%) 1
    HYPOXIA 0/4 (0%) 0 1/32 (3.1%) 1
    PLEURAL EFFUSION 0/4 (0%) 0 1/32 (3.1%) 1
    Vascular disorders
    HEMATOMA 0/4 (0%) 0 1/32 (3.1%) 1
    THROMBOEMBOLIC EVENT 0/4 (0%) 0 1/32 (3.1%) 1
    Other (Not Including Serious) Adverse Events
    Dose Level I: Treatment (Ofatumumab, Dinaciclib) Dose Level II: Treatment (Ofatumumab, Dinaciclib)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/4 (100%) 32/32 (100%)
    Blood and lymphatic system disorders
    Anemia 3/4 (75%) 7 28/32 (87.5%) 54
    Lymphode Pain 0/4 (0%) 0 6/32 (18.8%) 8
    Gastrointestinal disorders
    Abdominal pain 1/4 (25%) 1 2/32 (6.3%) 2
    Bloating 0/4 (0%) 0 3/32 (9.4%) 5
    Constipation 1/4 (25%) 2 11/32 (34.4%) 15
    Diarrhea 1/4 (25%) 1 12/32 (37.5%) 18
    Dyspepsia 0/4 (0%) 0 6/32 (18.8%) 7
    Mucositis 0/4 (0%) 0 4/32 (12.5%) 5
    Nausea 1/4 (25%) 1 10/32 (31.3%) 12
    Oral Dysesthesia 0/4 (0%) 0 3/32 (9.4%) 4
    Oral Pain 0/4 (0%) 0 3/32 (9.4%) 3
    Vomiting 2/4 (50%) 2 4/32 (12.5%) 5
    General disorders
    Chills 1/4 (25%) 1 3/32 (9.4%) 3
    Fatigue 2/4 (50%) 2 15/32 (46.9%) 18
    Fever 1/4 (25%) 1 2/32 (6.3%) 2
    General Disorders and Administration site Conditions-other 1/4 (25%) 1 0/32 (0%) 0
    Infusion Related Reactions 0/4 (0%) 0 3/32 (9.4%) 3
    Pain 3/4 (75%) 3 6/32 (18.8%) 6
    Infections and infestations
    Lung Infection 0/4 (0%) 0 2/32 (6.3%) 3
    Skin Infection 0/4 (0%) 0 2/32 (6.3%) 4
    Upper Respiratory Infection 0/4 (0%) 0 3/32 (9.4%) 4
    Injury, poisoning and procedural complications
    Ankle Fracture 1/4 (25%) 1 0/32 (0%) 0
    Bruising 1/4 (25%) 1 2/32 (6.3%) 2
    Fracture 1/4 (25%) 1 0/32 (0%) 0
    Investigations
    Alanine Aminotransferase Increased 2/4 (50%) 5 9/32 (28.1%) 14
    Alkaline Phosphatase Increased 0/4 (0%) 0 12/32 (37.5%) 28
    Aspartate Aminotransferase Increased 2/4 (50%) 5 9/32 (28.1%) 24
    Blood Bilirubin Decreased 1/4 (25%) 1 4/32 (12.5%) 6
    Creatinine Increased 0/4 (0%) 0 11/32 (34.4%) 19
    Investigations-Other 0/4 (0%) 0 2/32 (6.3%) 2
    Lymphocyte Count Decreased 2/4 (50%) 5 20/32 (62.5%) 57
    Lymphocyte Count Increased 2/4 (50%) 3 14/32 (43.8%) 21
    Neutrophil Count Decreased 4/4 (100%) 10 26/32 (81.3%) 91
    Platelet Count Decreased 4/4 (100%) 4 23/32 (71.9%) 48
    Weight Gain 0/4 (0%) 0 2/32 (6.3%) 2
    Weight Loss 0/4 (0%) 0 3/32 (9.4%) 3
    White Blood Cell Decreased 2/4 (50%) 4 22/32 (68.8%) 87
    Hypercalcemia 0/4 (0%) 0 5/32 (15.6%) 8
    Hyperglycemia 4/4 (100%) 10 31/32 (96.9%) 84
    Hyperkalemia 0/4 (0%) 0 8/32 (25%) 8
    Hypermagnesemia 1/4 (25%) 1 2/32 (6.3%) 2
    Hypernatremia 0/4 (0%) 0 3/32 (9.4%) 3
    Hyperuricemia 0/4 (0%) 0 7/32 (21.9%) 10
    Hypoalbuminemia 3/4 (75%) 5 19/32 (59.4%) 23
    Hypocalcemia 3/4 (75%) 5 18/32 (56.3%) 37
    Hypoglycemia 0/4 (0%) 0 6/32 (18.8%) 7
    Hypokalemia 2/4 (50%) 3 17/32 (53.1%) 21
    Hypomagnesemia 2/4 (50%) 3 7/32 (21.9%) 20
    Hyponatremia 1/4 (25%) 2 11/32 (34.4%) 13
    Hypophosphatemia 1/4 (25%) 2 24/32 (75%) 45
    Musculoskeletal and connective tissue disorders
    Back Pain 0/4 (0%) 0 4/32 (12.5%) 5
    Bone Pain 0/4 (0%) 0 3/32 (9.4%) 3
    Musculoskeletal and connective tissue disorder 1/4 (25%) 1 0/32 (0%) 0
    Myalgia 1/4 (25%) 1 8/32 (25%) 9
    Neck Pain 0/4 (0%) 0 2/32 (6.3%) 3
    Pain in Extremity 1/4 (25%) 1 2/32 (6.3%) 2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, Malignant and unspecified 0/4 (0%) 0 2/32 (6.3%) 2
    Nervous system disorders
    Dizziness 0/4 (0%) 0 5/32 (15.6%) 6
    Dysesthesia 0/4 (0%) 0 10/32 (31.3%) 11
    Dysgeusia 0/4 (0%) 0 3/32 (9.4%) 3
    Headache 1/4 (25%) 1 9/32 (28.1%) 9
    Paresthesia 2/4 (50%) 2 4/32 (12.5%) 4
    Peripheral sensory neuropathy 2/4 (50%) 2 2/32 (6.3%) 2
    Psychiatric disorders
    Insomnia 0/4 (0%) 0 4/32 (12.5%) 5
    Restlessness 0/4 (0%) 0 2/32 (6.3%) 2
    Renal and urinary disorders
    Chronic kidney disease 0/4 (0%) 0 2/32 (6.3%) 3
    Proteinuria 1/4 (25%) 1 0/32 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 0/4 (0%) 0 3/32 (9.4%) 3
    Cough 2/4 (50%) 3 5/32 (15.6%) 7
    Dyspnea 0/4 (0%) 0 7/32 (21.9%) 8
    Epistaxis 0/4 (0%) 0 2/32 (6.3%) 2
    Hypoxia 1/4 (25%) 1 0/32 (0%) 0
    Nasal congestion 1/4 (25%) 1 1/32 (3.1%) 1
    Productive cough 0/4 (0%) 0 7/32 (21.9%) 8
    Sore throat 0/4 (0%) 0 2/32 (6.3%) 2
    Hyperhidrosis 1/4 (25%) 1 0/32 (0%) 0
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 0/4 (0%) 0 7/32 (21.9%) 8
    Skin and subcutaneous tissue disorders 0/4 (0%) 0 2/32 (6.3%) 2
    Vascular disorders
    Hypertension 0/4 (0%) 0 22/32 (68.8%) 45
    Hypotension 0/4 (0%) 0 2/32 (6.3%) 2

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Jeffrey Jones, MD
    Organization The Ohio State University Comprehensive Cancer Center
    Phone 614-293-3507
    Email Jeffrey.Jones@osumc.edu
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01515176
    Other Study ID Numbers:
    • NCI-2012-00101
    • NCI-2012-00101
    • OSU-11120
    • OSU11120
    • CDR0000721353
    • OSU 11120
    • 9031
    • N01CM00070
    • N01CM62207
    • P30CA016058
    • P50CA140158
    • U01CA076576
    • UM1CA186712
    First Posted:
    Jan 23, 2012
    Last Update Posted:
    Mar 15, 2018
    Last Verified:
    Feb 1, 2018