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Study of TG-1801 in Subjects With B-Cell Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03804996
Recruitment Status : Recruiting
First Posted : January 15, 2019
Last Update Posted : September 15, 2020
Sponsor:
Information provided by (Responsible Party):
TG Therapeutics, Inc.

Brief Summary:
Phase 1 first in human Study to Assess the Bispecific Antibody TG-1801 in Subjects with B-Cell Lymphoma

Condition or disease Intervention/treatment Phase
B-Cell Lymphoma Drug: TG-1801 Biological: Ublituximab Phase 1

Detailed Description:
This is an open-label, multi-center, accelerated titration design study. Planned enrollment includes 1 subject at low dose levels. Subjects will receive weekly infusions of TG-1801 in a 4 week-cycles.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 First-in-Human Study of Bispecific Antibody TG-1801 in Subjects With B-Cell Lymphoma
Actual Study Start Date : March 5, 2019
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: TG-1801
Arm Description: TG-1801 will be administered once every 4 weeks (28-day) cycles. Subjects who experience disease progression after completing 6 months of single agent TG-1801 will be eligible for TG-1801 single-agent re-treatment at the discretion of the investigator.
Drug: TG-1801
Intravenous infusion over 1 hour every 4 weeks

Experimental: TG-1101
Arm Description: TG-1801 will be administered once every 4 weeks (28-day) cycles. To explore the safety of TG-1801 in combination with ublituximab will be explored at doses below and up to the RP2D. TG-1801 intrapatient dose escalation will not be permitted in combination therapy.
Drug: TG-1801
Intravenous infusion over 1 hour every 4 weeks

Biological: Ublituximab
"recombinant chimeric anti-CD20 monoclonal antibody, available in 25 mg/mL administered as an IV infusion once every 4 weeks"
Other Names:
  • TG-1101
  • LFB-R603




Primary Outcome Measures :
  1. Identification of Recommended Dose [ Time Frame: 18 months of therapy ]
    To determine the recommended Phase 2 dose (RP2D) by identifying dose limiting toxicity (DLT), maximum tolerable dose (MTD), and optimum biologic dose (OBD).

  2. Characterize the Safety Profile of TG-1801 [ Time Frame: 18 months of therapy ]
    To characterize the safety profile of TG-1801 alone and in combination with ublituximab by evaluating the adverse event profile.


Secondary Outcome Measures :
  1. Pharmacokinetic data collection [ Time Frame: 6 months of therapy ]
    To evaluate the pharmacokinetics (PK) of TG-1801 including Cmax.

  2. Anticancer activity Evaluation [ Time Frame: 6 months of therapy ]
    To evaluate the preliminary anticancer activity of TG-1801 by evaluating the single-agent arm by assessing the populations of lymphocytes by flow cytometry.



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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. Histologically confirmed B-cell lymphoma, relapsed to or refractory after at least one prior standard therapy. For subjects with aggressive lymphoma: those who are non-candidates for high-dose therapy or autologous stem cell transplant. Refractory is defined as disease progression during or within 6 months of the most recent prior therapy, while relapsed is defined as disease progression greater than 6 months after the most recent prior therapy.
  2. Measurable disease defined as at least 1 measurable disease lesion ≥ 1.5 cm in at least one diameter by CT/CT-PET or magnetic resonance imaging (MRI) in an area of no prior radiation therapy, or in an area that was previously irradiated that has documented progression.
  3. Be able to provide a core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy at Screening.
  4. Adequate organ function defined as:

    1. Absolute neutrophil count (ANC) > 1,000/µL and platelet count > 75,000/µL. Platelet requirements cannot be met by use of recent transfusion (within 30 days of study treatment initiation [Cycle 1 Day 1]). Growth factor support (e.g. G-CSF) is not allowed within 2 weeks prior to treatment initiation.
    2. Total bilirubin ≤ 1.5 times the ULN, or direct bilirubin ≤ ULN for subjects with total bilirubin > 1.5 ULN.
    3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN if no liver involvement or ≤ 5 x the ULN if known liver involvement.
    4. Calculated creatinine (Cr) clearance (CL) > 30 mL/min (as calculated by the Cockcroft-Gault or MDRD formula, 24-hour urine Cr CL also acceptable).
  5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  6. Male or female ≥ 18 years of age.
  7. Female subjects who are not of child-bearing potential (see Appendix B- Contraceptive Guidelines and Pregnancy), and female subjects of child-bearing potential who have a negative serum pregnancy test within 3 days prior to Cycle 1, Day 1. Female subjects of child-bearing potential, and male partners must consent to use a medically acceptable method of contraception throughout the study period and for 4 months after the last dose of study drug. Men of reproductive potential may not participate unless they agree to use medically acceptable contraception.
  8. Willingness and ability to comply with trial and follow-up procedures and provide written informed consent.

Exclusion Criteria:

  1. Prior therapy with any agent blocking the CD47/SIRPα pathway or any previous CD19 targeting therapy, including but not limited to: antibodies, fragments, bispecific bodies, or chimeric antigen receptor (CAR) T-cells.
  2. Subjects receiving cancer therapy (i.e. chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization) or any investigational drug within 21 days of Day 1 of Cycle 1 (42 days for prior mitomycin C or a nitrosourea).

    a. Corticosteroid therapy started at least 7 days prior to Cycle 1 Day 1 (prednisone ≤ 10 mg daily or equivalent) is allowed as clinically warranted. Topical or inhaled corticosteroids are permitted.

  3. Prior autologous stem cell transplant within 6 months. Prior allogeneic hematologic stem cell transplant within 1 year and excluded if there is active graft versus host disease.
  4. Subjects who have not recovered (≤ Grade 1 or at baseline) from adverse events due to previous therapy, except for alopecia and Grade 2 neuropathy due to previous cancer therapy.

    Note: Toxicity that has not recovered to ≤ Grade 1 is allowed if it meets the inclusion requirements for laboratory parameters defined above.

  5. Any severe or uncontrolled illness or other conditions that could affect their participation in the study including, but not limited to:

    1. Symptomatic, or history of documented congestive heart failure (NY Heart Association functional classification III-IV) - See Appendix C.
    2. Myocardial infarction within 6 months of enrollment.
    3. Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident, transient ischemic attack, angioplasty, cardiac/vascular stenting within 6 months of enrollment, angina not well controlled by medication.
    4. Ongoing or active infection, except localized fungal infection of skin or nails.
  6. Known active Hepatitis B (e.g. HBsAg reactive), Hepatitis C (e.g. HCV RNA [qualitative] is detected), cytomegalovirus (CMV DNA by PCR), or known history of HIV - See Appendix D.
  7. Malignancy within 2 years of study enrollment except for adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, superficial bladder cancer, or localized prostate cancer.
  8. Known clinically active CNS involvement.
  9. History of anaphylaxis or severe allergy to a monoclonal antibody; or known or suspected hypersensitivity to the excipients contained in the study drug formulation.
  10. Lactating or pregnant.

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): NCT03804996


Contacts
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Contact: TG Therapeutics Clinical Support Team 212-554-4484 clinicalsupport@tgtxinc.com

Locations
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Australia
Olivia Newton-John Cancer Wellness & Research Centre Recruiting
Heidelberg, Australia
The Alfred Hospital Completed
Melbourne, Australia
TG Therapeutics Investigational Trial Site Recruiting
Nedlands, Australia, 6009
Sponsors and Collaborators
TG Therapeutics, Inc.
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Responsible Party: TG Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03804996    
Other Study ID Numbers: TG-1801-101
First Posted: January 15, 2019    Key Record Dates
Last Update Posted: September 15, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by TG Therapeutics, Inc.:
relapsed or refractory
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin