A Multi-center Phase I/Ib Study Evaluating the Efficacy and Safety of Ublituximab, a Third- Generation Anti-CD20 Monoclonal Antibody, in Combination with TGR-1202, a Novel PI3k Delta Inhibitor and Ibrutinib in Patients with B-cell Malignancies.
The goal of this clinical research study is to learn the highest tolerable dose of the combination of ublituximab and TGR-1202 or the combination of ublituximab, TGR-1202, and ibrutinib that can be given to patients with B-cell lymphoma. The safety of this study drug combination will also be studied.
Disease Group: Lymphoma
Treatment Agent: Ibrutinib,TGR-1202,Ublituximab
Treatment Location: Both at MDACC & and Other Sites
Sponsor: TG Therapeutics, Inc.
Primary Objectives To evaluate the safety, and determine the dose limiting toxicities (DLT’s) and the maximum tolerated dose (MTD) of ublituximab in combination with TGR-1202 in patients with B-cell lymphoma To evaluate the safety, and determine the DLT’s and MTD of ublituximab + TGR-1202 + ibrutinib in patients with B-cell lymphoma Secondary Objectives To determine the overall response rate (ORR) defined as the sum of complete responses (CR) and partial responses (PR), progression-free survival (PFS), and duration of response (DOR) in patients with B-cell lymphoma.
IRB Review and Approval Date: 08/21/2014
Recruitment Status: Open
Projected Accrual: 240
1) Histologically confirmed B-cell non-Hodgkin lymphoma (NHL), chronic
lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and other
B-cell lymphoproliferative disorders as approved by the Medical Monitor
or Study Chair
2) Disease status defined as: a. NHL Cohorts: Refractory to or relapsed after at least 1 prior treatment regimen b. CLL/SLL Cohorts: Patients previously untreated or with relapsed or refractory disease
3) Patients must have measurable or evaluable disease
4) Adequate organ system function, defined as follows: a. Absolute neutrophil count (ANC)>/= 0.75 x 109/L b. Platelets >/=50 x 109/L: (Patients who have bone marrow infiltration are eligible if their ANC is > 500 or their platelet level is > 30,000) c. Total bilirubin </=1.5 times the upper limit of normal (ULN) d. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </=2.5 x ULN if no liver involvement or </=5 x the ULN if known liver involvement e. Creatinine 2.0 mg/dL OR calculated creatinine clearance 50 mL/min (as calculated by the Cockcroft-Gault method)
5) ECOG performance status </=2
6) Patients must be >/=18 years of age
7) Ability to swallow and retain oral medication
8) Female patients who are not of child-bearing potential, and female patients of child-bearing potential who have a negative serum pregnancy test within 5 days prior to initial trial treatment. Female patients of child-bearing potential, and all male partners must consent to use a medically acceptable method of contraception throughout the study period and for 30 days after the last dose of either study drug.
9) Willingness and ability to comply with trial and follow-up procedures, give written informed consent
1) Patients currently 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 Cycle 1/Day 1, or within 14 days of Cycle 1/Day 1 for limited
palliative radiation. a. Corticosteroid therapy started at least 7 days
prior to study entry (prednisone </=10 mg daily or equivalent) is
allowed as clinically warranted. Topical or inhaled corticosteroids are permitted.
2) Autologous hematologic stem cell transplant within 3 months of study entry. Allogeneic hematologic stem cell transplant within 12 months. Patients must not have active graft versus-host disease.
3) Evidence of active Hepatitis B or C infection (negative serology required) and/or known history of HIV
4) Patient has received wide field radiotherapy (including therapeutic radioisotopes such as strontium-89) within 28 days of Cycle 1/Day 1 or has not recovered from side effects of such therapy
5) Primary central nervous system lymphoma or known intracranial involvement, leptomeningeal metastases or spinal cord compression due to disease
6) Patients requiring treatment with strong CYP3A inhibitors (ibrutinib cohort only)
7) Known history of drug-induced liver injury, alcoholic liver disease, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver or portal hypertension
8) Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: a. Symptomatic, or history of documented congestive heart failure (New York Heart Association functional classification III-IV) b. QTcF >470 msec c. Angina not well-controlled by medication d. Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac or vascular stenting in the past 6 months
9) Presence of other active cancers, or history of treatment for invasive cancer within preceding 2 years. Patients with stage I cancer who have received definitive local treatment at least 2 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. noninvasive) are eligible, as are patients with history of non-melanoma skin cancer.
10) Women who are pregnant or lactating
11) Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol
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