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First-in-Human (FIH) Trial of GEN3009 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas

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ClinicalTrials.gov Identifier: NCT04358458
Recruitment Status : Recruiting
First Posted : April 24, 2020
Last Update Posted : August 26, 2020
Sponsor:
Information provided by (Responsible Party):
Genmab

Brief Summary:
The aim of this first-in-human trial is to characterize the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic characteristics of GEN3009 (DuoHexabody®-CD37) in subjects with relapsed/refractory B-cell Non-Hodgkin Lymphoma (NHL).

Condition or disease Intervention/treatment Phase
B-cell Non-Hodgkin Lymphoma Drug: GEN3009 Phase 1 Phase 2

Detailed Description:

This trial is a first-in-human (FIH), open-label, multicenter trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of GEN3009 in subjects with relapsed/refractory B-cell NHL (both aggressive and indolent subtypes).

The trial will be conducted in 2 parts; Dose Escalation and Dose Expansion. In the Dose Escalation part, GEN3009 will be administered by intravenous (IV) infusions at various dose levels in 28-day cycles. Dose Limiting Toxicity (DLT) will be assessed during the first treatment cycle and the Maximum Tolerated Dose (MTD) will be identified. Additional subjects will be treated in the Dose Expansion at the Recommended Phase 2 Dose (RP2D).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of GEN3009 (DuoHexaBody®-CD37) in Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma - A First-in-Human, Open-label, Phase 1/2a Dose Escalation Trial With Dose Expansion Cohorts
Actual Study Start Date : March 24, 2020
Estimated Primary Completion Date : November 30, 2022
Estimated Study Completion Date : May 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Treatment Administered Drug: GEN3009
GEN3009 will be administered by intravenous (IV) infusions at various dose levels in 28-day cycles. Expansion cohorts will be treated at the Recommended Phase 2 Dose (RP2D).
Other Name: DuoHexaBody®-CD37




Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: DLTs are assessed during the first treatment cycle (28 days) in each cohort. ]
    Dose liming toxicity (DLT) will be monitored to determine the maximum tolerated dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) of GEN3009.

  2. Adverse events [ Time Frame: AEs are collected throughout study until the end of the safety follow-up period (30 days after last dose). ]
    Incidence of treatment-emergent adverse events (AEs) as assessed by National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0

  3. Safety laboratory parameters (hematology) [ Time Frame: Safety laboratory data are collected at baseline, during all study cycles until the end of the safety follow-up period (30 days after last dose). ]
    CTCAE Grade changes from Baseline of hematology parameters: Hemoglobin, hematocrit, white blood cells including differential, neutrophils, basophils, eosinophils, absolute and percentage of lymphocytes, monocytes, reticulocytes, platelets, proportion of prolymphocytes.

  4. Safety laboratory parameters (biochemistry) [ Time Frame: Safety laboratory data are collected at baseline, during all study cycles until the end of the safety follow-up period (30 days after last dose). ]
    CTCAE Grade changes from Baseline of biochemistry parameters: albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bicarbonate, lactate dehydrogenase (LDH), calcium, chloride, magnesium, inorganic phosphorus (phosphate), sodium, potassium, creatinine, total bilirubin, blood urea nitrogen (BUN) or urea, uric acid, glucose, total protein, C reactive protein, D-dimer, ferritin.

  5. Safety laboratory parameters (coagulation) [ Time Frame: Safety laboratory data are collected at baseline, during all study cycles until the end of the safety follow-up period (30 days after last dose). ]
    CTCAE Grade changes from Baseline of coagulation parameters: International normalized ratio (INR), activated partial thromboplastin time (aPTT), and fibrinogen.

  6. Safety laboratory parameters (Immunoglobulins) [ Time Frame: Safety laboratory data are collected at baseline, during each treatment cycle, and at time of treatment discontinuation ]
    CTCAE Grade changes from Baseline of Immunoglobulins IgA, IgG, IgM

  7. Safety laboratory parameters (urinalysis) [ Time Frame: Safety laboratory data are collected at baseline, during each treatment cycle, and at time of treatment discontinuation ]
    CTCAE Grade changes from baseline of urinalysis parameters: pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase, specific gravity, urine pregnancy testing as applicable.

  8. Vital signs (body temperature) [ Time Frame: Vital signs are collected throughout study until the end of the safety follow-up period (30 days after last dose). ]
    Changes in body temperature will be measured by degrees Celsius (°C)

  9. Vital signs (blood pressure) [ Time Frame: Vital signs are collected throughout study until the end of the safety follow-up period (30 days after last dose). ]
    Changes in systolic and diastolic blood pressure will be measured by millimetres of mercury (mmHg)

  10. Vital signs (heart rate) [ Time Frame: Vital signs are collected throughout study until the end of the safety follow-up period (30 days after last dose). ]
    Changes in heart rate will be measured by beats per minute.

  11. Vital signs (oxygen saturation) [ Time Frame: Vital signs are collected throughout study until the end of the safety follow-up period (30 days after last dose). ]
    Changes in oxygen saturation will be measured by peripheral oxygen saturation (SpO2)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Be at least 18 years of age.
  2. Must sign an informed consent form prior to any screening procedures.
  3. Has histologically or cytologically confirmed relapsed and/or refractory B-cell NHL with no available standard therapy or is not a candidate for available standard therapy, and for whom, in the opinion of the investigator, experimental therapy with GEN3009 may be beneficial. All subjects must have received at least two prior lines of systemic therapy.
  4. Has one of the specified subtypes for B-cell NHL for the Dose Escalation and Dose Expansion parts of the study.
  5. Has measurable disease for B-cell NHL or has active disease for Chronic Lymphocytic Leukemia (CLL).
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  7. Has adequate hepatic, renal, and bone marrow functions.
  8. Before the first dose of GEN3009, during the trial, and for 12 months after the last dose of GEN3009, a woman must be either not of childbearing potential or of childbearing potential and practicing a highly effective method of birth control, and must have a negative serum beta-human chorionic gonadotropin (beta-hCG) and urine pregnancy test at screening.
  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.

Exclusion Criteria:

  1. Prior treatment with a CD37-targeting agent.
  2. Prior allogeneic Hematopoietic Stem Cell Transplantation (HSCT).
  3. Autologous HSCT within 3 months before the first dose of GEN3009.
  4. Treatment with an anti-cancer biologic including anti-CD20 therapy, radio-conjugated or toxin-conjugated antibody or chimeric antigen receptor (CAR) T-cell therapy within 4 weeks or 5 half-lives, whichever is shorter, before the first dose of GEN3009.
  5. Chemotherapy or radiation therapy within 2 weeks of the first dose of GEN3009.
  6. Treatment with an investigational drug or an invasive investigational medical device within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of GEN3009.
  7. Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
  8. Received a cumulative dose of corticosteroids more than the equivalent of 250 mg of prednisone within the 2-week period before the first dose of GEN3009.
  9. Has uncontrolled intercurrent illness.
  10. Toxicities from previous anti-cancer therapies have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy.
  11. Primary central nervous system (CNS) lymphoma or known CNS involvement at screening.
  12. Known past or current malignancy other than inclusion diagnosis,
  13. Has had major surgery within 3 weeks before screening or will not have fully recovered from surgery, or has major surgery planned during the time the subject is expected to participate in the trial (or within 4 weeks after the last dose of GEN3009).
  14. Known history/positive serology for hepatitis B.
  15. Known medical history or ongoing hepatitis C infection that has not been cured.
  16. HIV tested positive at screening.
  17. Is 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 GEN3009.
  18. Is a man who plans to father a child while enrolled in this trial or within 12 months after the last dose of GEN3009.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04358458


Contacts
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Contact: Genmab A/S Trial Information +4570202728 clinicaltrials@genmab.com

Locations
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United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Contact: Ben Burtness       Ben.Burtness@sarahcannon.com   
Principal Investigator: Michael Tees         
United States, Ohio
University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Adaora Adigwe       adaora.adigwe@uhhospitals.org   
Principal Investigator: Paolo Caimi         
Ohio State University Active, not recruiting
Columbus, Ohio, United States, 43210
Spain
ICO Badalona - Hospital Universitari Germans Trias i Pujol Active, not recruiting
Badalona, Barcelona, Spain, 08916
ICO l'Hospitalet - Hospital Duran i Reynals Active, not recruiting
Barcelona, L'Hospitalet De Llobregat, Spain, 08908
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Ana Rodrigues Mafalda       amafaldanrodrigues@vhio.net   
Principal Investigator: Pau Abrisqueta Costa         
Sponsors and Collaborators
Genmab
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Responsible Party: Genmab
ClinicalTrials.gov Identifier: NCT04358458    
Other Study ID Numbers: GCT3009-01
First Posted: April 24, 2020    Key Record Dates
Last Update Posted: August 26, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases