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

Status

Not yet recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2016-004339-19-PL

Enrollment

500

Registered

2017-01-25

Start date

2017-02-16

Completion date

Unknown

Last updated

2022-01-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Lymphocytic Leukemia MedDRA version: 21.0 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864

Interventions

Product Name: Ublituximab Product Code: TG-1101 Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: UBLITUXIMAB CAS Number: 1174014-05-1 Current Sponsor code: TG-1101 Other

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1.Prior treatment in clinical trial UTX-TGR-304 a.Confirmed progression by IRC from Arms B, C, or D after at least two cycles of treatment in trial UTX-TGR-304. There is no required timeframe to begin treatment on the UTX-TGR-204 protocol; however, if other therapies to treat the disease are implemented in the interim, the subject will not be eligible to enroll in the study. b.Non-progressing subjects 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 103/mm3 (0.75 K/µL) mL of blood / platelet count > 40 x 103/mm3 (40 K/µL) mL of blood unless cytopenias are related to bone marrow involvement. b.Total bilirubin =1.5 times the upper limit of normal (ULN) with the exception of Gilbert's Disease and Autoimmune Hemolytic Anemia. 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 Modified Cockcroft-Gault formula (using ideal body mass [IBM]). 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 250 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 250

Exclusion criteria

Exclusion criteria: 1.Prior treatment with obinutuzumab + chlorambucil (Arm B subjects) or ublituximab (Arm C subjects) within 7 days of Cycle 1/Day 1. 2.Subjects 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 chronic active Hepatitis B defined as Hepatitis B surface antigen positive or Hepatitis B DNA positive by PCR (HBV, NOT including subjects with prior hepatitis B vaccination who are Hepatitis B surface antibody positive only;) or chronic active Hepatitis C infection (HCV) defined as Hepatitis C RNA positive by PCR, cytomegalovirus (CMV) DNA positive by PCR, or known history of HIV. If HBc antibody, HCV antibody or CMV IgG and/or IgM antibody is positive the subject must be evaluated for the presence of HBV, HCV, or CMV by PCR - See Appendix D. 5.Evidence of ongoing systemic bacterial, fungal or viral infection, except localized fungal infections of skin or nails. NOTE: Subjects may be receiving prophylactic antiviral or antibacterial therapies at investigator discretion. Use of anti-pneumocystis pneumonia prophylaxis is required prior to Cycle 1/Day 1 and for the first 2 cycles. After cycle 2, is per investigator discretion. 6.Woman who are pregnant or lactating. 7.Live virus vaccines four (4) weeks prior to or during ublituximab therapy.

Design outcomes

Primary

Measure	Time frame
Main Objective: For subjects previously on Arms B, C, & D of Study UTX-TGR-304: To observe the overall response rate (ORR) defined as the sum of complete responses (CR) and partial responses (PR) For subjects previously on Arm A of Study UTX-TGR-304: To evaluate the progression-free survival (PFS) and duration of response (DOR);Secondary Objective: For subjects previously on Arms B, C, & D of Study UTX-TGR-304: • To observe the progression-free survival (PFS) and duration of response (OR) • To observe the % of subjects that achieve MRD negativity • To observe the safety of ublituximab in combination with TGR-1202 For subjects previously on Arm A of Study UTX-TGR-304: To evaluate the safety of Ublituximab in combination with TGR-1202;Primary end point(s): 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 subjects who achieve a CR. 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. Minimal Residual Disease (MRD) Negativity Rate MRD negativity rate is defined as the proportion of subjects who are MRD negative. 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.;Timepoint(s) of evaluation of this end point: During the study period, all subjects will be evaluated for response by CT and/or MRI. Evaluations are to be obtained at approximately cycles 3, 6 and 12. Following cycle 12, evaluations should occur	—

Measure

Time frame

Main Objective: For subjects previously on Arms B, C, & D of Study UTX-TGR-304: To observe the overall response rate (ORR) defined as the sum of complete responses (CR) and partial responses (PR) For subjects previously on Arm A of Study UTX-TGR-304: To evaluate the progression-free survival (PFS) and duration of response (DOR);Secondary Objective: For subjects previously on Arms B, C, & D of Study UTX-TGR-304: • To observe the progression-free survival (PFS) and duration of response (OR) • To observe the % of subjects that achieve MRD negativity • To observe the safety of ublituximab in combination with TGR-1202 For subjects previously on Arm A of Study UTX-TGR-304: To evaluate the safety of Ublituximab in combination with TGR-1202;Primary end point(s): 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 subjects who achieve a CR. 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. Minimal Residual Disease (MRD) Negativity Rate MRD negativity rate is defined as the proportion of subjects who are MRD negative. 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.;Timepoint(s) of evaluation of this end point: During the study period, all subjects will be evaluated for response by CT and/or MRI. Evaluations are to be obtained at approximately cycles 3, 6 and 12. Following cycle 12, evaluations should occur

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Secondary

Measure	Time frame
Secondary end point(s): For subjects 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. 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. Minimal Residual Disease (MRD) Negativity Rate MRD negativity rate is defined as the proportion of patients who are MRD negative. For subjects 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 subjects will be evaluated for response by CT and/or MRI. Evaluations are to be obtained at approximately cycles 3, 6 and 12. Following cycle 12, evaluations should occur at least every 12 cycles unless clinically indicated more frequently. The determination of response and progression will be based on IWCLL criteria (Hallek M, 2008) by the treating investigator	—

Measure

Time frame

Secondary end point(s): For subjects 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. 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. Minimal Residual Disease (MRD) Negativity Rate MRD negativity rate is defined as the proportion of patients who are MRD negative. For subjects 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 subjects will be evaluated for response by CT and/or MRI. Evaluations are to be obtained at approximately cycles 3, 6 and 12. Following cycle 12, evaluations should occur at least every 12 cycles unless clinically indicated more frequently. The determination of response and progression will be based on IWCLL criteria (Hallek M, 2008) by the treating investigator

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Countries

Italy, Poland, Spain, United Kingdom, United States

Contacts

Public ContactIzabela Kozdras

Brillance Sp. z o.o.

ikozdras@brillance.pl+48668166876

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026