Summary

for people ages 18 years and up (full criteria)
at San Diego, California and other locations
study started
estimated completion:

Description

Summary

Phase 1b (Dose Escalation) in primarily CLL/SLL patients will evaluate safety and pharmacology of self-administered twice a day oral doses beginning at 25 mg/dose for 4 weeks with succeeding cohorts at escalating doses until establishing dose limiting toxicity or, recommended Phase 2 dose. Patient data will be assessed before authorizing dose escalation cohorts. Phase 2 (Cohort Expansion) will follow in cohorts using the recommended dose to explore clinical activity, safety, pharmacology of SNS-062 (vecabrutinib) as monotherapy.

Official Title

A Phase 1b/2 Dose-Escalation and Cohort-Expansion Study of the Noncovalent, Reversible Bruton's Tyrosine Kinase Inhibitor, SNS-062, in Patients With B-Lymphoid Malignancies

Details

Phase 1b (Dose Escalation) This portion of the study will evaluate the safety and pharmacology of a range of SNS-062 (vecabrutinib) dose levels administered to subjects with previously treated B-lymphoid malignancies, including: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytoid lymphoma/Waldenström's macroglobulinemia (LPL/WM), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma of the activated B-cell subtype (DLBCL-ABC), and follicular lymphoma (FL).

All subjects will self-administer SNS-062 orally BID. The dose-limiting toxicity (DLT) window will be 4 weeks (1 cycle in length). Assessments on study will be performed in 4-week cycles. Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels of SNS-062 using a standard 3+3 dose-escalation design.

Based on the pattern of dose-limiting toxicities (DLTs) observed in the first cycle (4 weeks), escalation will proceed to define a maximum tolerated dose (MTD) and/or a recommended dose (RD) that may be the MTD or a lower dose. An additional 6 subjects may be accrued at the MTD or the RD to confirm SNS-062 safety and pharmacology as a prelude to further clinical evaluation. Assessments regarding DLTs and dose escalation will be performed by a Safety Review Committee (SRC) comprising, but not limited to, the principal investigators, the medical monitor and the study sponsor drug safety representative.

Phase 2 (Cohort Expansion) This portion of the study provides cohort expansion to further explore the clinical activity, safety, and pharmacology of SNS-062 monotherapy. Accrual will occur independently for each of the 4 disease and mutation-specific cohorts. Subjects will self-administer SNS-062 orally at the RD of SNS-062 identified in the Phase 1b portion of the study. The SRC will meet regularly to assess the efficacy and safety for each cohort.

Keywords

Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Lymphoplasmacytoid Lymphoma Mantle-Cell Lymphoma Waldenstrom Macroglobulinemia Diffuse Large B Cell Lymphoma Follicular Lymphoma CLL hematological diseases relapsed cancer malignancy SNS-062 B-lymphoid Waldenström's macrogloulinemia mantle cell lymphoma SLL LPL WM MCL refractory DLBCL-ABC DLBCL diffuse large B-cell lymphoma CLL/SLL Lymphoma Lymphoma, Follicular Leukemia, Lymphoid Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma, B-Cell Lymphoma, Mantle-Cell Lymphoma, Large B-Cell, Diffuse

Eligibility

You can join if…

Open to people ages 18 years and up

(Key factors listed):

  • Eastern Cooperative Oncology Group Performance Status of ≤2.
  • Confirmed malignancy with relapsed/refractory disease after ≥2 lines of standard systemic therapy including prior BTK inhibitor therapy having CLL, LPL/WM or MCL and for DLBCL-ABC and FL, after ≥2 lines of standard systemic therapy.
  • Presence of measurable disease through various assessments depending on specific cancer type.
  • Current medical need for therapy of the B-lymphoid malignancy due to disease-related symptoms, lymphadenopathy, organomegaly, extranodal organ involvement, or PD.

You CAN'T join if...

(Key factors listed):

  • Known central nervous system malignancy.
  • History of other malignancies except for some which have been adequately treated(e.g., local cancers of the skin, cervix or breast cancers, non-invasive bladder cancer, prostate or other cancers of stages 1 or 2 in complete remission).
  • Significant cardiovascular disease or electrocardiogram (ECG) abnormalities
  • Ongoing risk for bleeding due to bleeding diathesis, platelet function disorder,uncontrolled peptic ulcer disease, oral anticoagulation medications.
  • Evidence of uncontrolled systemic bacterial, fungal or viral infections at the start of drug therapy.
  • Demonstrated intolerance to BTK inhibitor as shown by discontinuation due to adverse effects.
  • Use of a moderate or strong inhibitor or inducer of CYP3A4 within 7 days prior to start of study therapy (e.g., some antibiotics, antifungals, anticonvulsants,grapefruit).

Locations

  • UC San Diego Moores Cancer Center accepting new patients
    San Diego California 92093 United States
  • University of California Irvine Medical Center accepting new patients
    Orange California 92868-3201 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Sunesis Pharmaceuticals
ID
NCT03037645
Phase
Phase 1/2
Study Type
Interventional
Last Updated