A Multi-Center, Open-Label, Extension Study of Ublituximab (TG-1101) in Combination with TGR-1202 for Patients Previously Enrolled in Protocol UTX-TGR-304

• Register: EUCTR
• Last refreshed on: 14 May 2018
• Main ID: EUCTR2016-004339-19-GB
• Date of registration: 08/05/2018
• Prospective Registration: No
• Primary sponsor: TG Therapeutics
• Public title: A Multi-Center, Open-Label, Extension Study of Ublituximab (TG-1101) in Combination with TGR-1202 for Patients Previously Enrolled in Protocol UTX-TGR-304
• Scientific title: A Multi-Center, Open-Label, Extension Study of Ublituximab (TG-1101) in Combination with TGR-1202 for Patients Previously Enrolled in Protocol UTX-TGR-304
• Date of first enrolment: 09/05/2017
• Target sample size: 242
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004339-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, Italy, Poland, Spain, United Kingdom, United States

Contacts

• Name: Pallav Shah
• Affiliation: Cambridge Regulatory Services

• Name: Pallav Shah
• Affiliation: Cambridge Regulatory Services

Key inclusion & exclusion criteria

Inclusion criteria:
1. Prior treatment in clinical trial UTX-TGR-304
a. Confirmed progression by IRC from either Arms B, C, or D after at least two cycles of treatment in trial UTX-TGR-304
b. Non-progressing patients from Arm A may be eligible for enrollment when protocol UTX-TGR-304 is completed
2. Adequate organ system function, defined as follows:
a. Absolute neutrophil count (ANC) > 750 X 1000 /mm3 (0.75 K/uL) mL of blood/ platelet count > 40 X 1000/mm3 (40 K/uL) mL of blood
b. Total bilirubin =1.5 times the upper limit of normal (ULN)
c. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5 x ULN if no liver involvement or =5 x the ULN if known liver involvement
d. Calculated creatinine clearance >30 mL/min (as calculated by the Cockcroft-Gault formula)
3. ECOG performance status = 2
4. Ability to swallow and retain oral medication
5. Willingness and ability to comply with trial and follow-up procedures, give written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 6
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion criteria:
1. Prior treatment with obinutuzumab + chlorambucil (Arm B patients) or ublituximab (Arm C patients) within 7 days of Cycle 1/Day 1.
2. Patients refractory to (progressing on) UTX-TGR-304 Treatment Arm A (ublituximab + TGR-1202).
3. Known histological transformation from CLL to an aggressive lymphoma (i.e. Richter’s transformation).
4. Evidence of ongoing systemic bacterial, fungal or viral infection, except localized fungal infections of skin or nails. NOTE: Patients may be receiving prophylactic antiviral or antibacterial therapies at investigator discretion. Use of anti-pneumocystis pneumonia prophylaxis is encouraged.
5. Woman who are pregnant or lactating.
6. Live virus vaccines four (4) weeks prior to or during ublituximab therapy.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Chronic Lymphocytic Leukemia
MedDRA version: 20.1 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864

Intervention(s)

Product Name: Ublituximab
Product Code: TG-1101
Pharmaceutical Form: Solution for injection
INN or Proposed INN: UBLITUXIMAB
Current Sponsor code: TG-1101
Other descriptive name: IgG1 immunoglobulins
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Product Name: TGR-1202
Product Code: TGR-1202
Pharmaceutical Form: Tablet
INN or Proposed INN: TGR-1202
Current Sponsor code: TGR-1202
Other descriptive name: (S)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1H-pyrazolo [3, 4-d] pyrimidin-1- yl)-ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one 4 methylbenzenesulfonate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Primary end point(s): For patients previously on Arms B, C, & D of Study UTX-TGR-304:
Overall response rate (ORR)
ORR is defined as sum of CR and PR rates.
Complete Response (CR) Rate
CR rate is defined as the proportion of patients who achieve a CR.

For patients previously on Arm A of Study UTX-TGR-304:
Progression-free survival (PFS)
PFS is defined as the interval from enrollment to the earlier of the first documentation of definitive disease progression or death from any cause.
Definitive disease progression based on standard criteria (Hallek et al. 2008) and occurring for any reason (i.e., increasing lymphadenopathy, organomegaly or bone marrow involvement; decreasing platelet count, hemoglobin, or neutrophil count; or worsening of disease-related symptoms) other than lymphocytosis.
Duration of response (DOR)
DOR is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause.

Secondary Objective: For patients previously on Arms B, C, & D of Study UTX-TGR-304:
To evaluate the progression-free survival (PFS) and duration of response (DOR)
To evaluate the % of patients that achieve MRD negativity

For patients previously on Arm A of Study UTX-TGR-304:
To evaluate the safety of ublituximab in combination with TGR-1202

Main Objective: For patients previously on Arms B, C, & D of Study UTX-TGR-304:
To determine the overall response rate (ORR) defined as the sum of complete responses (CR) and partial responses (PR)

For patients previously on Arm A of Study UTX-TGR-304:
To evaluate the progression-free survival (PFS) and duration of response (DOR)

Timepoint(s) of evaluation of this end point: During the study period, all patients will be evaluated for response by CT and/or MRI. Evaluations are to be obtained following the completions of cycles 3, 6, 9 12, 15, 18 and every 3 cycles thereafter. All efficacy assessments have a +/- 7 day window. The determination of response and progression will be based on IWCLL criteria (Hallek M, 2008) by the treating investigator. Scans may be collected and confirmed by central independent radiology group in select cases.

Secondary Outcome(s)

Secondary end point(s): For patients previously on Arms B, C, & D of Study UTX-TGR-304:
Progression-free survival (PFS)
PFS is defined as the interval from enrollment to the earlier of the first documentation of definitive disease progression or death from any cause.
Duration of response (DOR)
Definitive disease progression based on standard criteria (Hallek et al. 2008) and occurring for any reason (i.e., increasing lymphadenopathy, organomegaly or bone marrow involvement; decreasing platelet count, hemoglobin, or neutrophil count; or worsening of disease-related symptoms) other than lymphocytosis.
DOR is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause.
Minimal Residual Disease (MRD) Negativity Rate
MRD negativity rate is defined as the proportion of patients who are MRD negative.

For patients previously on Arm A of Study UTX-TGR-304:
Safety
All Adverse Events (AE's) will be reported and evaluated using National Cancer Institute's Common Terminology Criteria (CTCAE) v4.0.

Timepoint(s) of evaluation of this end point: During the study period, all patients will be evaluated for response by CT and/or MRI. Evaluations are to be obtained following the completions of cycles 3, 6, 9 12, 15, 18 and every 3 cycles thereafter. All efficacy assessments have a +/- 7 day window. The determination of response and progression will be based on IWCLL criteria (Hallek M, 2008) by the treating investigator. Scans may be collected and confirmed by central independent radiology group in select cases.

Secondary ID(s)

2016-004339-19-ES

UTX-TGR-204

Source(s) of Monetary Support

TG Therapeutics