Clinical trial NCT02594384: A Phase I Dose Escalation Study of the Safety and Pharmacokinetics of LAM-002A In Patients With Non-Hodgkin's Lymphoma
Official title: A Phase 1 Dose Escalation Study of the Safety and Pharmacokinetics of LAM-002A (Apilimod Dimesylate Capsules) Administered Orally in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic
Keywords: Phase 1
Safety
Apilimod dimesylate
Pharmacokinetics
Non-Hodgkin Lymphoma
Chronic lymphocytic leukemia
Lead sponsor: OrphAI Therapeutics
Sponsor class: INDUSTRY
First posted: 2015-11-03
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 1 dose-exploration study of LAM-002A administered by mouth in patients with relapsed or refractory B-cell NHL. Safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD),and preliminary anti-tumor activity will be evaluated.

Detailed description: LAM-002A is supplied as 25-mg or 50-mg capsules and will be administered two times daily or three times daily by mouth in repeated 28-day cycles. Patients will be advised to take the doses at the same time each day.

A 3 + 3 design will be utilized to define a maximum tolerated dose (MTD). The MTD is defined as the highest dose at which no more than 1 of 6 patients (i.e., \< 33%) experiences a dose-limiting toxicity (DLT) in the dose cohort.

Once the dose and schedule are established, additional patients will be treated to better characterize the safety, tolerability,PK, PD, and anti-tumor activity of LAM-002A when administered alone or in combination with rituximab or atezolizumab.

Eligibility criteria: Inclusion Criteria:

1. Able to understand and comply with the protocol requirements and has signed the informed consent document.
2. Confirmed diagnosis of B-cell Non-Hodgkin's lymphoma limited to follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), primary mediastinal B-cell lymphoma (PMBL), or chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) that has progressed and for which standard curative measures do not exist or are no longer effective. Prior therapy must have included a rituximab-based regimen.
3. Patients with DLBCL: Cancer progression after transplant, or be unwilling, unable or not an appropriate candidate for an autologous stem cell or bone marrow transplant
4. Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of 1 or more lesions that measure at least 2.0 cm in the longest dimension (as assessed radiographically)
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or less.
6. Adequate organ and marrow function.
7. Able to swallow oral capsules without difficulty.
8. Acceptable birth control.
9. Women of childbearing potential : negative pregnancy test
10. Adequate archival or fresh tumor tissue (from biopsy, bone marrow, or peripheral blood) for analysis of potential predictive biomarkers.

Exclusion Criteria:

1. Patients with central nervous system (CNS) lymphoma are not eligible for the trial unless the disease had been treated and the subject remains without symptoms with no active CNS lymphoma.
2. Not recovered from toxicity due to all prior therapies.
3. Other uncontrolled significant illness.
4. History of malabsorption or other gastrointestinal (GI) disease that may significantly alter the absorption of LAM-002A
5. Major surgery within 28 days prior to first dose of study drug.
6. Past history of tuberculosis (TB) or active infection with TB, human immunodeficiency virus (HIV), hepatitis B or hepatitis C.
7. Lactation or breast feeding.
8. Unable or unwilling to abide by the study protocol or cooperate fully with the Investigator or designee.

This is a shortened list and additional criteria may apply.

Primary outcomes:
measure: Determination of the Maximum Tolerated Dose (MTD) of Continuous Oral LAM-002A
timeFrame: 28 days
Secondary outcomes:
measure: Peak Plasma Concentration (Cmax) of LAM-002A
timeFrame: 8 days
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A
timeFrame: 8 days
measure: Objective Response Rate
timeFrame: 1 cycle (28 days) up to a maximum of 24 cycles
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Clearview Cancer Institute
state: Alabama
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute at Emory University
state: Georgia
city: Lafayette
country: United States
facility: Horizon Oncology Research, Inc.
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
Study officials:
affiliation: AI Therapeutics
name: Langdon Miller, MD
role: STUDY_DIRECTOR
References: