Chronic Lymphocytic Leukemia Clinical Trial
A Study of NX-2127 in Adults With Relapsed/Refractory B-cell Malignancies
This is a first-in-human Phase 1a/1b multicenter, open-label oncology study designed to evaluate the safety and anti-cancer activity of NX-2127 in patients with advanced B-cell malignancies.
Phase 1a is a dose escalation to evaluate the safety and tolerability of NX-2127 in adult patients with relapsed/refractory (R/R) B-cell malignancies, who have required and received at least 2 prior systemic therapies (or at least 1 prior therapy for patients with WM or PCNSL) and for whom no other therapies are known to provide clinical benefit. Phase 1b will investigate the efficacy of NX-2127 at the dose selected in Phase 1a in up to 5 cohorts of patients with R/R B-cell malignancy indications who have received at least 2 prior systemic therapies (or at least 1 prior therapy for patients with WM or PCNSL):
Chronic Lymphocytic Leukemia (leukemia-cll/" >CLL) or Small Lymphocytic Lymphoma (SLL) with no BTK C481 mutation
BTK C481 mutation-positive CLL/SLL
Mantle Cell Lymphoma (MCL)
Follicular lymphoma (FL) or Marginal Zone Lymphoma (MZL); Primary Central Nervous System Lymphoma (PCNSL)
Non-germinal center B cell type (non-GCB) Diffuse Large B-cell Lymphoma (DLBCL) or Waldenstrom Macroglobulinemia (WM)
Patients must be ≥ 18 years of age
Patients must have measurable disease per disease-specific response criteria
Patients with indolent forms of NHL must meet the criteria requiring systemic treatment (i.e., iwCLL, IWG, Lugano Classification of Lymphoma response criteria, or International PCNSL Collaborative Group response criteria)
Patients with transformed lymphoma are eligible for the study with the exception of those who have prolymphocytic leukemia, MCL with blastoid histology, MCL with pleomorphic morphology, or MCL with known TP53 mutation
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (non-PCNSL indications) or 0 - 2 (PCNSL patients)
Adequate organ and bone marrow function
Patients of child-bearing potential must use adequate contraceptive measures to avoid pregnancy for the duration of the study as defined in the protocol
Inclusion Criteria for Patients in Phase 1a:
Have histologically confirmed R/R CLL, SLL, WM, MCL, and MZL, FL(grade 1 - 3b), non-GCB DLBCL, or PCNSL
Received at least 2 prior systemic therapies (or at least 1 prior therapy for patients with WM or PCNSL) and have no other therapies known to provide clinical benefit
Must require systemic therapy
Inclusion Criteria for Patients in Phase 1b:
Must have one of the following histologically documented R/R B-cell malignancies:
CLL/SLL with no BTK C481 mutation whose disease has failed treatment with a BTKi;
BTK C481 mutation-positive CLL/SLL whose disease has failed treatment with a BTKi;
MCL whose disease has failed treatment with BTKi and an anti-CD20 mAb-based regimen
FL (grade 1 - 3b) or MZL whose disease has failed treatment with anti-CD20 mAb-based regimen; or PCNSL whose disease failed treatment with a BTKi
Non-GCB DLBCL whose disease has failed treatment with an anti-CD20 mAb-based regimen and an anthracycline (either progressed post stem cell transplant or transplant-ineligible) or WM whose disease has failed treatment with BTKi
History of central nervous system (CNS) lymphoma/leukemia in remission for less than 2 years (non-PCNSL indications) or evidence of disease outside of the CNS (other than ocular involvement) or disease involving the brain stem (PCNSL patients)
Active, uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia
History of known/suspected other autoimmune disease (exception(s): patients with alopecia, vitiligo, resolved childhood atopic dermatitis, hypothyroidism, or hyperthyroidism that is clinically euthyroid at screening are allowed.)
Unable to swallow capsules or have a condition that may interfere in the delivery, absorption, or metabolism of the study drug
Bleeding diathesis, or other known risk for acute blood loss
Patients requiring ongoing treatment with warfarin or an equivalent vitamin K antagonist and within 7 days prior to the first dose of study drug
Prior radiotherapy within 2 weeks of planned start of study drug (excluding limited palliative radiation)
Toxicities from previous anticancer therapies must have resolved to baseline levels or to Grade 1 (except for alopecia, hypothyroidism with adequate replacement therapy, hypopituitarism with adequate replacement therapy, peripheral neuropathy or hematologic parameters meeting inclusion criteria).
Active known second malignancy
Patient has had major surgery (e.g. requiring general anesthesia) within 4 weeks before the planned first dose of study drug
Infection with human immunodeficiency virus (HIV)-1 or HIV-2. Exception: patients with well-controlled HIV (e.g., CD4 > 350/mm3 and undetectable viral load) are eligible.
Current active liver disease from any cause
Active viral reactivation (e.g., CMV or EBV)
Use of systemic corticosteroids exceeding 20 mg/day prednisone (or equivalent) for non-PCNSL indications within 15 days prior to the planned start of study drug. PCNSL patients may not exceed corticosteroid doses of 40 mg/day prednisone (or equivalent) and should be on a stable or decreasing dose for 7 days prior to planned study start.
Use of non-steroidal immunosuppressive drugs within 30 days, prior to start of the study
Clinically significant, uncontrolled cardiac, cardiovascular disease, or history of myocardial infarction within 6 months of planned start of study drug
Administration of any strong cytochrome P450 3A (CYP3A) inducers or inhibitors for 14 days prior to the first dose of study drug, and any P-glycoprotein inhibitors or moderate inducers of CYP3A for 7 days
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There are 13 Locations for this study
Duarte California, 91010, United States
Orange California, 92868, United States
San Francisco California, 94143, United States
Denver Colorado, 80218, United States
Sarasota Florida, 34203, United States
Chicago Illinois, 60637, United States
Bethesda Maryland, 20814, United States
New York New York, 10065, United States
Cincinnati Ohio, 45267, United States
Columbus Ohio, 43210, United States
Nashville Tennessee, 37203, United States
Houston Texas, 77030, United States
Seattle Washington, 98104, United States
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