Clinical trial NCT02440685: A Phase 1/2 Study To Evaluate ASN002 In Relapsed/Refractory Lymphoma And Advanced Solid Tumors
Official title: A Phase 1/2, Open-Label, Uncontrolled, Multiple Dose Escalation, Cohort Expansion Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Preliminary Efficacy Of ASN002 In Relapsed/Refractory Lymphoma, Myelofibrosis, Chronic Lymphocytic Leukemia, And Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Lymphoma, Large B-Cell, Diffuse
Lymphoma, Mantle-Cell
Lymphoma, Follicular
Cancer
Neoplasm
Tumor
Lymphoma, Malignant
Lymphoma, B-cell
Lymphoma, Non-Hodgkin
B-Cell Chronic Lymphocytic Leukemia
B-Cell Leukemia, Chronic
B-Lymphocytic Leukemia, Chronic
Chronic Lymphocytic Leukemia
Leukemia, Lymphocytic, Chronic
Leukemia, Lymphocytic, Chronic, B Cell
Myelofibrosis
Chronic Idiopathic Myelofibrosis
Idiopathic Myelofibrosis
Lymphoma, T Cell, Peripheral
Peripheral T-Cell Lymphoma
T-Cell Lymphoma, Peripheral
Keywords: DLBCL
FL
MCL
PTCL
MF
CLL
Lead sponsor: Asana BioSciences
Sponsor class: INDUSTRY
First posted: 2015-05-12
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study terminated early so no all groups per protocol were conducted
Primary purpose: TREATMENT

Brief summary: This study is a dose escalation, and cohort expansion study in subjects with advanced cancer for which no standard therapy exists. Subjects must have received prior treatment for cancer that has not worked, or has stopped working.

Detailed description: The study will be conducted in two parts. Part A is a dose escalation study to determine a safe and tolerable dose of ASN002 for subjects with relapsed or refractory lymphoma, or advanced solid tumors. Part A will also characterize the pharmacokinetics and pharmacodynamics of ASN002 through blood sampling. Subjects in Part B will enroll subjects with four types of lymphoma Diffuse Large B-cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL) and Peripheral T-cell lymphoma (PTCL). Additional groups of subjects with Myelofibrosis (MF) and Chronic Lymphocytic Leukemia (CLL) will be enrolled. Subjects will be treated with the highest safe and tolerable dose determined in Part A of the study to determine preliminary efficacy. Subjects may continue to receive ASN002 for up to 1 year in the absence of severe side effects or disease progression.

Eligibility criteria: Inclusion Criteria:

* Written informed consent obtained prior to any study-related procedure being performed;
* Male or female subjects at least 18 years of age at the time of consent;
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2;
* Recovered from the reversible effects of prior antineoplastic therapy (with the exception of alopecia and Grade 1 neuropathy).
* Screening blood counts of the following: Absolute neutrophil count ≥ 1000/μL, Platelets ≥ 75,000/μL, Hemoglobin ≥ 8 g/dL (with transfusion support);
* Screening chemistry values of the following: Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3.0 × upper limit of the normal (ULN), total bilirubin ≤ 1.5 × ULN, Creatinine ≤ 1.5 × ULN;
* At screening, life expectancy of at least 3 months;
* Subject is willing and able to comply with all protocol required visits and assessments;
* Male and female subjects of child-bearing potential must agree to use medically acceptable methods of birth control throughout the study and for thirty (30) days after the last dose of study medication.
* (Part A only) Histologically or cytologically confirmed metastatic and/or advanced solid tumors or lymphomas for which no standard therapy exists, or who are not eligible for standard treatment. Subjects must have received at least one prior therapy for their malignancy;
* (Part B only) Histologically confirmed DLBCL/MCL/FL/PTCL/MF/CLL on the basis of excisional lymph node or extranodal tissue biopsy; diagnosis of relapsed/refractory disease defined as 1) recurrence of disease after a Complete Response (CR), or 2) Partial Response (PR), Stable Disease (SD) at completion of treatment regimen preceding entry into study, subjects must not be candidates for standard therapy, subjects who have not received Stem Cell Translplant (SCT) must be ineligible to receive SCT.

Exclusion Criteria

* Have received prior chemotherapy regimens within 4 weeks of Day 1;
* Have received prior treatment with monoclonal antibodies within 6 weeks of first dose of Day 1;
* Have had major surgery within 30 days prior to the start of Day 1;
* Received any investigational treatment within 4 weeks prior to the start of study medication;
* Have had an infection requiring the use of parenteral antibiotics within 14 days prior to the start of Day 1;
* Have known central nervous system metastasis or Central Nervous System lymphoma;
* Is receiving high dose corticosteroids (\>10 mg prednisone daily or equivalent);
* Has known bleeding diathesis that would be a safety risk;
* Has a history of other malignancy within the 3 years prior to screening, except adequately treated basal cell or squamous cell carcinoma of the skin, or carcinoma in-situ;
* Has difficulty swallowing medications, or known history of malabsorption syndrome;
* Has a serious concurrent medical condition, such as: congestive heart failure New York Heart Association (NYHA) class III or IV or uncontrolled hypertension at screening, 12-Lead electrocardiogram (ECG) abnormalities considered by the investigator to be clinically significant including myocardial infarction, angioplasty, or cardiac stent placement within the last 6 months, HIV infection, known Hepatitis B or C infection. Subjects at high risk for Hepatitis B or C infection should have serology testing to rule out infection, a medical condition requiring the therapeutic use of anticoagulants.
* Known hypersensitivity to ASN002 or its excipients;
* Prior participation, i.e., receipt of study medication, in this study;
* Any condition that, in the opinion of the investigator, would impair the subject's ability to comply with study procedures;
* Female subjects that are pregnant or lactating.
* Part B only: Prior treatment with SYK or Janus Kinase (JAK) inhibitors, except MF subjects.

Primary outcomes:
measure: Objective Response Rate
timeFrame: First 29 days
Secondary outcomes:
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Arizona Oncology
state: Arizona
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute - Emory
state: Georgia
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: START - Midwest
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Buenos Aires
country: Argentina
facility: Hospital Universitario Austral
state: Derqui, Pilar
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Instituto Alexander Fleming
Study officials:
affiliation: Asana BioSciences
name: Niranjan Rao, PhD
role: STUDY_DIRECTOR
References: