This research study will be evaluating the safety and efficacy of a study drug called TGR-1202 in combination with a known drug ibrutinib, also known as Imbruvica, as a possible treatment for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Mantle Cell Lymphoma (MCL) that has come back or that has not responded to standard treatment.
This research study is a Phase I and Ib combination clinical trial, which aims to both evaluate the safety of an investigational drug combination and also tries to define the appropriate dose of the investigational drug to evaluate in later clinical trials. "Investigational" means that the intervention is being studied. It also means that the FDA (U.S. Food and Drug Administration) has not approved TGR-1202 in the United States for use in MCL/CLL/SLL cancers. TGR-1202 is a newly developed drug that may stop cancer cells from growing based on recent laboratory experiments. The results from these experiments suggest this drug may help to kill cancer cells when coupled with ibrutinib. In this research study, the safety and tolerability of TGR-1202 is being investigated to determine the highest dose that can safely be used in combination with ibrutinib. The study is also aimed to evaluate whether TGR-1202 has any effect on tumor growth (nodal response), and to determine the overall repsonse rate and duration of response in patients with CLL/SLL or MCL
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Pacific Cancer Care
Monterey, California, United States
St. Francis Hospital and Cancer Center
Hartford, Connecticut, United States
Eastern Maine Medical Center/ Northern Light Cancer Care
Brewer, Maine, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Number of Patients Who Experienced a Dose Limiting Toxicity (DLT) During Phase I
To assess the safety of TGR1202 in combination with ibrutinib relapsed or refractory CLL or MCL. DLT is based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. DLT refers to toxicities experienced at any time during the study treatment, defined as Grade 4 anemia; Grade 4 neutropenia lasting \>7 days (while receiving growth factor support); Grade 4 thrombocytopenia lasting \> 7 days; Grade ≥3 febrile neutropenia; and Grade ≥3 thrombocytopenia with Grade \>2 hemorrhage;Grade ≥ 3 non-hematologic toxicity unresponsive to standard supportive care measure with the exception of asymptomatic Grade ≥3 lab abnormalities that resolve to ≤ Grade 1 or baseline within 7 days;treatment delay of ≥14 days due to unresolved toxicity; and non-hematologic toxicity of Grade 2 (at any time during treatment) that, in the judgment of the Investigators, Study Chair, and the Medical Monitor, is dose-limiting.
Time frame: Participants were assessed every week or more often as needed during Cycle 1 or more often for up to 28 days to assess Dose-limiting toxicities (DLTs) during Phase I
Overall Response Rate (ORR)
The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on the 2008 IW-CLL criteria for CLL (Hallek et al., 2008) by Lugano Criteria ( Cheson et al,.24) for MCL.
Time frame: At baseline, End of Cycle 2, End of Cycle 5, End of Cycle 9, End of Cycle 14 and approximately q6 months until C26, then investigator discretion thereafter
Rate of Nodal Partial Response With Lymphocytosis (nPR)
nPR will only be evaluated in CLL patients, defined as percentage of patients achieved nodal PR. As per Cheson et al., 2012, patients who achieve a radiographic PR but continue to have a lymphocytosis with \>5,000 B-lymphocytes per μL are considered to have a nodular partial response, also known as PR with lymphocytosis, due to the fact that they appear to derive a similar clinical benefit from BCR inhibitors as patients who achieve a traditional PR.
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Beth Israel Deaconness Medical Center
Boston, Massachusetts, United States
Time frame: At baseline, End of Cycle 2, End of Cycle 5, End of Cycle 9, End of Cycle 14 and approximately q6 months until C26, then investigator discretion thereafter
Median Progression-Free Survival (PFS)
Progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) or death, or is censored at time of last dsease assessment.
Time frame: Disease will be evaluated at baseline, cycle 1 day 1,8,15,22 and cycle 2 day 1,15, and cycle 3-6 on day1, and every 2 cycles until cycle 12, then every 3 cycles thereafter. In long-term follow-up, survival will be followed every 3 cycles up to 2 years.
Median Duration of Overall Response (DOR)
Duration of Overall Response (DOR), estimated using the Kaplan Meier method, is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) per 2008 IWCLL Criteria, until the first date that recurrent or progressive disease is objectively documented. Patients without progressive disease are censored at the date of last disease assessment.
Time frame: Disease response will be evaluated at baseline, cycle 1 day 1,8,15,22 and cycle 2 day 1,15, and cycle 3-6 on day1, and every 2 cycles until cycle 12, then every 3 cycles thereafter.