Mocetinostat (MGCD0103) Plus Brentuximab Vedotin (SGN-35) in Patients With Relapsed or Refractory Hodgkin Lymphoma

Sponsor
Memorial Sloan Kettering Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT02429375
Collaborator
MethylGene Inc. (Industry)
7
1
1
69.9
0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to find out how safe and effective treatment with a new combination of drugs, mocetinostat and brentuximab vedotin, is in treating cancer. There will be 2 parts to this trial: a phase I part and a phase II part.

Brentuximab vedotin is approved by the U.S. Food and Drug Administration (FDA) to be given to patients with Hodgkin Lymphoma. Mocetinostat is an experimental drug that has been given to patients with Hodgkin lymphoma in another clinical trial. When given alone, mocetinostat caused lymphoma to shrink in about 1 out of 4 patients with Hodgkin lymphoma. This is the first study that will give mocetinostat and brentuximab vedotin together.

Condition or Disease Intervention/Treatment Phase
  • Drug: Mocetinostat Plus Brentuximab Vedotin
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
7 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase IB/II Study of Mocetinostat (MGCD0103) Plus Brentuximab Vedotin (SGN-35) in Patients With Relapsed or Refractory Hodgkin Lymphoma
Actual Study Start Date :
Apr 22, 2015
Actual Primary Completion Date :
Feb 17, 2021
Actual Study Completion Date :
Feb 17, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Mocetinostat (MGCD0103) Plus Brentuximab Vedotin (SGN-35)

Patients with relapsed or refractory Hodgkin lymphoma will receive brentuximab vedotin combined with mocetinostat. For the phase I portion of the study, patients will be enrolled in a traditional 3 + 3 phase 1 design on sequential dosing cohorts in order to determine the maximum tolerated dose (MTD) of mocetinostat when given with brentuximab vedotin. Once the MTD is determined, (up to) an additional 26 patients will be enrolled on to the phase II portion of the study at the MTD to determine the response rate and toxicity associated with treatment. The phase Ib and II study will include a lead-in with mocetinostat alone for 1 week followed by the combined treatment beginning day 15 following initiation of mocetinostat.

Drug: Mocetinostat Plus Brentuximab Vedotin
All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in.
Other Names:
  • MGCD0103
  • SGN-35
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) [1 year]

      For this objective the standard 3+3 dose-escalation scheme will be used. Patients will be accrued to the study in cohorts of 3 (starting with dose level 1). For any given dose an initial cohort of 3 patients will be treated at that dose. The dose level will be escalated if none of the 3 patients exhibits any DLT

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) [1 year]

      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.

    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 CD30 positive relapsed or refractory Hodgkin lymphoma

    • Measurable disease, as defined by the International Harmonization Project.14

    • Patients must have failed autologous stem cell transplant or at least 2 prior cytotoxic regimens for Hodgkin lymphoma. Patients who have failed only 1 prior cytotoxic regimen for Hodgkin lymphoma are permitted to enroll as long as they are not eligible for autologous stem cell transplant.

    • Age ≥18

    • ECOG performance status ≤2 (Karnofsky ≥60%)

    • Patients must have normal organ and marrow function as defined below:

    • absolute neutrophil count ≥1,000/mcL

    • platelets ≥75,000/mcL

    • total bilirubin within normal institutional limits or < 3x the upper limit of normal in patients with Gilbert's disease

    • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

    • Creatinine ≤1.5 x institutional upper limit of normal OR creatinine clearance ≥40 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

    • QTc ≤ 500 ms

    • The effects of mocetinostat and brentuximab vedotin on the developing human fetus are potentially harmful. For this reason, 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. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of mocetinostat and brentuximab vedotin administration.

    • Patients with known HIV infection must have CD4 count greater than 200.

    Exclusion Criteria:
    • Presence of a small (or greater size) pericardial effusion; definitions of pericardial effusions by echocardiographic assessment.

    • Patients who have had chemotherapy or radiotherapy within 3 weeks prior to entering the study

    • Patients who have not recovered from adverse events due to agents administered more than 3 weeks earlier.

    • Patients who are receiving any other investigational agents.

    • Patients with known cerebral or meningeal involvement by lymphoma are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to mocetinostat or brentuximab vedotin.

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

    • Women who are pregnant or breastfeeding

    • Previous primary progression or grade 3 toxicity on treatment with brentuximab vedotin

    • Systemic steroids are allowed as long as they are tapered to the equivalent of 20mg prednisone daily or less by the start of cycle 2.

    • Platelet or packed red blood cell transfusion within 14 days of pre-treatment evaluation

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Memorial Sloan Kettering Cancer Center New York New York United States 10065

    Sponsors and Collaborators

    • Memorial Sloan Kettering Cancer Center
    • MethylGene Inc.

    Investigators

    • Principal Investigator: Alison Moskowitz, MD, Memorial Sloan Kettering Cancer Center

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Memorial Sloan Kettering Cancer Center
    ClinicalTrials.gov Identifier:
    NCT02429375
    Other Study ID Numbers:
    • 14-232
    First Posted:
    Apr 29, 2015
    Last Update Posted:
    May 12, 2022
    Last Verified:
    Mar 1, 2022
    Keywords provided by Memorial Sloan Kettering Cancer Center
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Dose Level 1: 50mg Mocetinostat Dose Level 2: 70mg Mocetinostat Dose Level 3: 90mg Mocetinostat
    Arm/Group Description Mocetinostat Plus Brentuximab Vedotin: All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in. Mocetinostat Plus Brentuximab Vedotin: All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in. Mocetinostat Plus Brentuximab Vedotin: All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in.
    Period Title: Overall Study
    STARTED 3 3 1
    COMPLETED 3 3 1
    NOT COMPLETED 0 0 0

    Baseline Characteristics

    Arm/Group Title Dose Level 1: 50mg Mocetinostat Dose Level 2: 70mg Mocetinostat Dose Level 3: 90mg Mocetinostat Total
    Arm/Group Description Mocetinostat Plus Brentuximab Vedotin: All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in. Mocetinostat Plus Brentuximab Vedotin: All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in. Mocetinostat Plus Brentuximab Vedotin: All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in. Total of all reporting groups
    Overall Participants 3 3 1 7
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    43
    30
    43
    33
    Sex: Female, Male (Count of Participants)
    Female
    1
    33.3%
    3
    100%
    0
    0%
    4
    57.1%
    Male
    2
    66.7%
    0
    0%
    1
    100%
    3
    42.9%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    1
    33.3%
    0
    0%
    1
    14.3%
    Not Hispanic or Latino
    3
    100%
    2
    66.7%
    1
    100%
    6
    85.7%
    Unknown or Not Reported
    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%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    3
    100%
    3
    100%
    1
    100%
    7
    100%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    United States
    3
    100%
    3
    100%
    1
    100%
    7
    100%

    Outcome Measures

    1. Primary Outcome
    Title Maximum Tolerated Dose (MTD)
    Description For this objective the standard 3+3 dose-escalation scheme will be used. Patients will be accrued to the study in cohorts of 3 (starting with dose level 1). For any given dose an initial cohort of 3 patients will be treated at that dose. The dose level will be escalated if none of the 3 patients exhibits any DLT
    Time Frame 1 year

    Outcome Measure Data

    Analysis Population Description
    Data were not collected
    Arm/Group Title Mocetinostat (MGCD0103) Plus Brentuximab Vedotin (SGN-35)
    Arm/Group Description Patients with relapsed or refractory Hodgkin lymphoma will receive brentuximab vedotin combined with mocetinostat.
    Measure Participants 0
    2. Secondary Outcome
    Title Overall Response Rate (ORR)
    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 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Level 1: 50mg Mocetinostat Dose Level 2: 70mg Mocetinostat Dose Level 3: 90mg Mocetinostat
    Arm/Group Description Mocetinostat Plus Brentuximab Vedotin: All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in. Mocetinostat Plus Brentuximab Vedotin: All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in. Mocetinostat Plus Brentuximab Vedotin: All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in.
    Measure Participants 3 3 1
    Progression of Disease
    2
    66.7%
    0
    0%
    1
    100%
    Partial Response
    0
    0%
    2
    66.7%
    0
    0%
    Stable Disease
    0
    0%
    1
    33.3%
    0
    0%
    NA - Patient Withdrawal of Consent
    1
    33.3%
    0
    0%
    0
    0%

    Adverse Events

    Time Frame 1 year
    Adverse Event Reporting Description
    Arm/Group Title Dose Level 1: 50mg Mocetinostat Dose Level 2: 70mg Mocetinostat Dose Level 3: 90mg Mocetinostat
    Arm/Group Description Mocetinostat Plus Brentuximab Vedotin: All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in. Mocetinostat Plus Brentuximab Vedotin: All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in. Mocetinostat Plus Brentuximab Vedotin: All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in.
    All Cause Mortality
    Dose Level 1: 50mg Mocetinostat Dose Level 2: 70mg Mocetinostat Dose Level 3: 90mg Mocetinostat
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 0/3 (0%) 1/1 (100%)
    Serious Adverse Events
    Dose Level 1: 50mg Mocetinostat Dose Level 2: 70mg Mocetinostat Dose Level 3: 90mg Mocetinostat
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/3 (33.3%) 0/3 (0%) 1/1 (100%)
    General disorders
    Malaise 0/3 (0%) 0/3 (0%) 1/1 (100%)
    Infections and infestations
    Infections and infestations - Other, specify 1/3 (33.3%) 0/3 (0%) 0/1 (0%)
    Metabolism and nutrition disorders
    Anorexia 0/3 (0%) 0/3 (0%) 1/1 (100%)
    Dehydration 0/3 (0%) 0/3 (0%) 1/1 (100%)
    Hypokalemia 0/3 (0%) 0/3 (0%) 1/1 (100%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 0/3 (0%) 0/3 (0%) 1/1 (100%)
    Other (Not Including Serious) Adverse Events
    Dose Level 1: 50mg Mocetinostat Dose Level 2: 70mg Mocetinostat Dose Level 3: 90mg Mocetinostat
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 3/3 (100%) 1/1 (100%)
    Blood and lymphatic system disorders
    Anemia 2/3 (66.7%) 2/3 (66.7%) 1/1 (100%)
    Gastrointestinal disorders
    Nausea 1/3 (33.3%) 0/3 (0%) 0/1 (0%)
    Diarrhea 1/3 (33.3%) 0/3 (0%) 0/1 (0%)
    General disorders
    Fatigue 2/3 (66.7%) 2/3 (66.7%) 0/1 (0%)
    Investigations
    White blood cell decreased 0/3 (0%) 2/3 (66.7%) 0/1 (0%)
    Platelet count decreased 0/3 (0%) 1/3 (33.3%) 0/1 (0%)
    Alanine aminotransferase increased 0/3 (0%) 1/3 (33.3%) 0/1 (0%)
    Aspartate aminotransferase increased 0/3 (0%) 1/3 (33.3%) 0/1 (0%)
    Neutrophil count decreased 0/3 (0%) 3/3 (100%) 1/1 (100%)
    Cholesterol high 0/3 (0%) 1/3 (33.3%) 0/1 (0%)
    INR increased 0/3 (0%) 0/3 (0%) 1/1 (100%)
    Lymphocyte count decreased 1/3 (33.3%) 1/3 (33.3%) 0/1 (0%)
    Metabolism and nutrition disorders
    Hyperglycemia 0/3 (0%) 0/3 (0%) 1/1 (100%)
    Hyponatremia 0/3 (0%) 0/3 (0%) 1/1 (100%)
    Anorexia 1/3 (33.3%) 0/3 (0%) 0/1 (0%)
    Hypertriglyceridemia 0/3 (0%) 1/3 (33.3%) 0/1 (0%)
    Hypoalbuminemia 0/3 (0%) 0/3 (0%) 1/1 (100%)
    Hypocalcemia 0/3 (0%) 1/3 (33.3%) 1/1 (100%)
    Hypokalemia 0/3 (0%) 0/3 (0%) 1/1 (100%)
    Hypophosphatemia 0/3 (0%) 0/3 (0%) 1/1 (100%)
    Nervous system disorders
    Peripheral sensory neuropathy 1/3 (33.3%) 0/3 (0%) 0/1 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 1/3 (33.3%) 0/3 (0%) 0/1 (0%)
    Vascular disorders
    Hypertension 1/3 (33.3%) 0/3 (0%) 0/1 (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/Title Dr. Alison Moskowitz, MD
    Organization Memorial Sloan Kettering Cancer Center
    Phone \646-608-3726
    Email moskowia@mskcc.org
    Responsible Party:
    Memorial Sloan Kettering Cancer Center
    ClinicalTrials.gov Identifier:
    NCT02429375
    Other Study ID Numbers:
    • 14-232
    First Posted:
    Apr 29, 2015
    Last Update Posted:
    May 12, 2022
    Last Verified:
    Mar 1, 2022