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Safety, PK, PD, and Antitumor Activity of Vecabrutinib (SNS-062) in B Lymphoid Cancers

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ClinicalTrials.gov Identifier: NCT03037645
Recruitment Status : Recruiting
First Posted : January 31, 2017
Last Update Posted : April 23, 2019
Sponsor:
Information provided by (Responsible Party):
Sunesis Pharmaceuticals

Brief Summary:
This is an open-label Phase 1b/2 study in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)or non hodgkin's lymphoma (NHL) who have failed prior standard of care therapies including a BTK inhibitor where one is approved for the indication.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Lymphoplasmacytoid Lymphoma Mantle-Cell Lymphoma Waldenstrom Macroglobulinemia Diffuse Large B Cell Lymphoma Follicular Lymphoma Marginal Zone Lymphoma Drug: SNS-062 Phase 1 Phase 2

Detailed Description:
This study includes 2 parts: phase 1 (dose escalation) and phase 2 (cohort expansion) in patients with CLL/SLL or NHL who have failed prior standard of care therapies including a BTK inhibitor where one is approved for the indication. NHL indications include lymphoplasmacytoid lymphoma/Waldenström's macroglobulinemia (LPL/WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma of the activated B-cell subtype (DLBCL-ABC), and follicular lymphoma (FL). In Phase 1b, cohorts of 3 to 6 patients are studied at each dose level, starting with 25 mg vecabrutnib BID in oral capsule form. Following identification of the MTD and/or recommended dose, in Phase 2 patients will be enrolled to expansion cohorts to further characterize the clinical activity, safety, pharmacology and of vecabrutinib. Cycle length is 4 weeks days.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 124 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 28, 2017
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : June 30, 2021


Arm Intervention/treatment
Experimental: Dose escalating cohorts of SNS-062
Sequential groups, 25, 50, 100, 200, 300, 400 and 500 mg twice daily on to determine maximum tolerated dose and recommended dose (RD) in the treatment of various hematological cancers followed by expansion of the recommended dose cohort in Phase 2 of the study treating hematological cancers.
Drug: SNS-062
SNS-062 will be orally administered twice daily and available in capsules containing either 25 mg or 100 mg of active ingredient.




Primary Outcome Measures :
  1. Maximum tolerated dose and/or Recommended dose of SNS-062 (Phase 1b) [ Time Frame: Up to approximately 21 months ]
    To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD)within the tested SNS-062 dose range. The MTD is the highest tested dose level at which ≥6 subjects have been treated and which is associated with a Cycle 1 dose limiting toxicity (DLT) in <33% of the subjects. The RD may be the MTD or may be a lower dose.

  2. Objective Response Rate (ORR) (Phase 2) [ Time Frame: Approximately 24 months ]

    Phase 2 portion of study measuring ORR and corresponding 95% confidence intervals by cohort. ORR will be defined by disease subtype as the proportion of subjects who achieve CLL/SLL: a CR, CRi, or PR.

    MCL: a CR or PR. MZL: a CR or PR. LPL/WM: a CR, VGPR, PR, or MR.



Secondary Outcome Measures :
  1. Safety as assessed through reported AEs, SAEs, DLTs and abnormal lab findings [ Time Frame: Up to approximately 24 months ]
    Type, severity, timing of onset, duration, and relationship to study drug of any TEAEs or abnormalities of laboratory tests, SAEs, DLTs, or AEs leading to study discontinuation.

  2. Characterization of Pharmacokinetics (AUC) [ Time Frame: Up to approximately 24 months ]
    Area Under the Curve (AUC)

  3. Characterization of Pharmacokinetics (Cmax) [ Time Frame: Up to approximately 24 months ]
    Maximum Plasma Concentration (Cmax)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (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, MCL or MZL 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.

Exclusion Criteria (Key factors listed):

  • Active central nervous system involvement.
  • History of second primary malignancy that has progressed or required systemic treatment in the past 2 years. Exceptions include: local cancers of the skin, cervix or breast cancers, non-invasive bladder cancer, hormone sensitive prostate cancer with stable PSA ≥3 months, and other localized solid tumors in situ/other low risk cancers.
  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03037645


Contacts
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Contact: Clinical Trials General Contact 650-266-3500 clinicaltrials@sunesis.com

Locations
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United States, California
University of California Irvine Medical Center Recruiting
Orange, California, United States, 92868-3201
UC San Diego Moores Cancer Center Recruiting
San Diego, California, United States, 92093
United States, Florida
Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Weill Cornell Medicine Recruiting
New York, New York, United States, 10065
United States, Oregon
Willamette Valley Cancer Institute and Research Center Recruiting
Eugene, Oregon, United States, 97401
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Sunesis Pharmaceuticals
Investigators
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Study Director: Renee Ward, MD, PhD Sunesis Pharmaceuticals

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Responsible Party: Sunesis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03037645     History of Changes
Other Study ID Numbers: 062-HEM-102
First Posted: January 31, 2017    Key Record Dates
Last Update Posted: April 23, 2019
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sunesis Pharmaceuticals:
CLL
hematological diseases
relapsed
cancer
malignancy
SNS-062
B-lymphoid
chronic lymphocytic leukemia
small lymphocytic lymphoma
lymphoplasmacytoid lymphoma
Waldenström's macrogloulinemia
mantle cell lymphoma
SLL
LPL
WM
MCL
refractory
DLBCL-ABC
DLBCL
follicular lymphoma
diffuse large B-cell lymphoma
CLL/SLL
MZL
marginal zone lymphoma

Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Follicular
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia
Leukemia, B-Cell
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders