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GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT04824794
Recruitment Status : Recruiting
First Posted : April 1, 2021
Last Update Posted : September 2, 2021
Sponsor:
Information provided by (Responsible Party):
Genmab

Tracking Information
First Submitted Date  ICMJE March 9, 2021
First Posted Date  ICMJE April 1, 2021
Last Update Posted Date September 2, 2021
Actual Study Start Date  ICMJE March 22, 2021
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 29, 2021)
  • Escalation: Dose limiting toxicities (DLTs) [ Time Frame: DLTs will be assessed during the first cycle (21 days) in each cohort ]
    Incidence of DLTs
  • Escalation: Adverse events [ Time Frame: AEs are collected throughout study until the end of the safety follow-up period (30 days after last dose). ]
    To assess the safety and tolerability of GEN3014 throughout the treatment period of patients participating in the trial
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2021)
  • Escalation: To establish the pharmacokinetic profile (PK) profile of GEN3014 [ Time Frame: Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] ]
    Maximum concentration of GEN3014 (Cmax) after dosing
  • Escalation: To establish the PK profile of GEN3014 [ Time Frame: Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] ]
    Time after dosing at which the maximum drug concentration was observed (Tmax)
  • Escalation: To establish the PK profile of GEN3014 [ Time Frame: Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] ]
    Time after dosing at which the lowest drug concentration is observed before the next dose is administered (C_Trough)
  • Escalation: To establish the PK profile of GEN3014 [ Time Frame: Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] ]
    Area-under-the-concentration-time curve from zero to last quantifiable sample(AUC_0-C last)
  • Escalation: To establish the PK profile of GEN3014 [ Time Frame: Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] ]
    Area-under-the-concentration-time curve from zero to 168 h (AUC_0-168 h)
  • Escalation: To establish the PK profile of GEN3014 [ Time Frame: Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] ]
    Accumulation ratios in Cmax (R_A, Cmax)
  • Escalation: To establish the PK profile of GEN3014 [ Time Frame: Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] ]
    Accumulation ratios in area-under-the-concentration-time curve (R_A, AUC)
  • Escalation: Evaluate immunogenicity of GEN3014 [ Time Frame: ADA are collected throughout trial until the end of the safety follow-up period (30 days after last dose) ]
    Anti-drug antibody response (ADA)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies
Official Title  ICMJE An Open-Label, Multicenter, Phase 1/2 Trial of GEN3014 (HexaBody®-CD38) in Relapsed or Refractory Multiple Myeloma and Other Hematologic Malignancies
Brief Summary This trial is an open-label, safety trial of GEN3014 (HexaBody®-CD38). The trial consists of two parts: a dose escalation part phase 1, first-in-human (FIH), and an expansion part phase 2a.
Detailed Description The purpose of the escalation part of the trial is to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D), as well as to establish the safety profile of GEN3014 (HexaBody®-CD38) in Relapsed or Refractory Multiple Myeloma and Other Hematologic Malignancies
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE Biological: GEN3014 (HexaBody®-CD38)
GEN3014 is administered by intravenous (IV) infusion
Study Arms  ICMJE Experimental: Treatment
GEN3014
Intervention: Biological: GEN3014 (HexaBody®-CD38)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 29, 2021)
152
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria (Escalation)

  1. Must be at least 18 years of age.
  2. Must sign an informed consent form (ICF) prior to any Screening procedures.
  3. Must have fresh bone marrow samples collected at Screening.
  4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0, 1, or 2.
  5. Has acceptable laboratory test results during the Screening period
  6. A woman of reproductive potential must agree to use adequate contraception during the trial and for 12 months after the last GEN3014 administration.
  7. A woman of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) at Screening.
  8. A woman must agree not to donate eggs (ova, oocytes) for assisted reproduction during the trial and for 12 months after receiving the last dose of GEN3014.
  9. A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control.

    Specific for RRMM:

  10. Must have documented multiple myeloma as defined by the criteria below and have evidence of disease progression on the most recent prior treatment regimen based on IMWG criteria:

    • Prior documentation of monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy-proven plasmacytoma.

    and

    • Measurable disease at baseline as defined by any of the following:

    • IgG, IgA, IgD, or IgM myeloma: Serum M-protein level ≥0.5 g/dL (≥5 g/L) or urine M protein level ≥200 mg/24 hours; Or
    • Light chain myeloma: Serum Ig free light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio

    Note: Subjects with RRMM must have exhausted standard therapies, at the investigator's discretion.

  11. For anti-CD38 mAb-naive RRMM Cohort: Subject received at least 3 prior lines of therapy including a PI and an IMiD in any order, or is double refractory to a PI and an IMiD; or subject received ≥ 2 prior lines of therapy if 1 of those lines included a combination of PI and IMiD. Note: Subjects should not have received any anti-CD38 antibody. Anti-CD38 mAb naive RRMM subjects will be recruited from countries where anti-CD38 therapies are not available.
  12. For anti-CD38 mAb-treated RRMM Cohort: Subject has received at least 2 prior lines of therapy and must have discontinued daratumumab or isatuximab for at least 4 weeks prior to the first dose of GEN3014. Note: Subjects should not have received any other anti-CD38 antibody except daratumumab or isatuximab.
  13. Potassium level ≥3.0 mEq/L (≥3.0 mmol/L); or corrected serum calcium ≤14.0 mg/dL (≤3.5 mmol/L).

Exclusion Criteria

  1. Prior treatment with an anti-CD38 antibody except daratumumab or isatuximab.
  2. Treatment with an anti-cancer agent, chemotherapy, radiation therapy, or major surgery within 2 weeks prior to the first dose of GEN3014.
  3. Treatment with an investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of GEN3014.
  4. Cumulative dose of corticosteroids more than the equivalent of ≥140 mg of prednisone within 2-week period before the first dose of GEN3014.
  5. Has clinically significant cardiac disease.
  6. Toxicities from previous anti-cancer therapies have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy.
  7. Primary central nervous system (CNS) tumor or known CNS involvement at Screening.
  8. Has known history/positive serology for hepatitis B
  9. Known medical history or ongoing hepatitis C infection that has not been cured.
  10. HIV positive at screening
  11. Currently receiving any other investigational agents.
  12. A woman who is pregnant or breast-feeding, or who is planning to become pregnant while enrolled in this trial or within 12 months after the last dose of GEN3014.
  13. A man who plans to father a child while enrolled in this trial or within 12 months after the last dose of GEN3014.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Genmab A/S Trial Information +45 70202728 clinicaltrials@genmab.com
Listed Location Countries  ICMJE Denmark,   Spain,   Sweden,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04824794
Other Study ID Numbers  ICMJE GCT3014-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Genmab
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Genmab
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Genmab
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP