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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03804996




Registration number
NCT03804996
Ethics application status
Date submitted
12/01/2019
Date registered
15/01/2019
Date last updated
8/04/2024

Titles & IDs
Public title
Study of TG-1801 in Subjects With B-Cell Lymphoma
Scientific title
A Phase 1 First-in-Human Study of Bispecific Antibody TG-1801 in Subjects With B-Cell Lymphoma
Secondary ID [1] 0 0
TG-1801-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-Cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TG-1801
Treatment: Other - Ublituximab

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.

Experimental: TG-1101 - Arm Description: TG-1801 and ublituximab will be administered once every 4 weeks (28-day cycle) for up to 6 cycles followed by TG-1801 monotherapy.

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.


Treatment: Drugs: TG-1801
Intravenous infusion over 1 hour every 4 weeks

Treatment: Other: Ublituximab
"recombinant chimeric anti-CD20 monoclonal antibody, available in 25 mg/mL administered as an IV infusion once every 4 weeks"
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Identification of Recommended Dose
Timepoint [1] 0 0
18 months of therapy
Primary outcome [2] 0 0
Characterize the Safety Profile of TG-1801
Timepoint [2] 0 0
18 months of therapy
Secondary outcome [1] 0 0
Pharmacokinetic data collection
Timepoint [1] 0 0
6 months of therapy
Secondary outcome [2] 0 0
Anticancer activity Evaluation
Timepoint [2] 0 0
6 months of therapy

Eligibility
Key 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, 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 administration of ublituximab and 30 days after last administration of TG-1801. 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior therapy with any agent blocking the CD47/SIRPa 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).
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.
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/02/2024
Sample size
Target
Accrual to date
Final
50
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
TG Therapeutics Investigational Trial Site - Heidelberg
Recruitment hospital [2] 0 0
TG Therapeutics Investigational Trial Site - Melbourne
Recruitment hospital [3] 0 0
TG Therapeutics Investigational Trial Site - Nedlands
Recruitment postcode(s) [1] 0 0
03084 - Heidelberg
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
06009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
TG Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Phase 1 first in human Study to Assess the Bispecific Antibody TG-1801 in Subjects with B-Cell Lymphoma
Trial website
https://clinicaltrials.gov/study/NCT03804996
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03804996