A Phase I Dose Escalation Study of the Safety and Pharmacokinetics of LAM-002A In Patients With Non-Hodgkin's Lymphoma (LAM-002A/NHL)

OrphAI Therapeutics

Status and phase: Completed; Phase 1

Conditions: Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic

Treatments: Drug: Rituximab; Drug: LAM-002A; Drug: Atezolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02594384

LAM-002A-NHL-CLN01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 62 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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62 participants in 4 patient groups

Continuous monotherapy

Experimental group

Description:

All patients will take LAM-002A two times daily by mouth every day until cancer progression or intolerability.

Treatment:

Drug: LAM-002A

Intermittent monotherapy

Experimental group

Description:

All patients will receive LAM-002A at escalating dose levels two times daily by mouth for 3 days on therapy followed by 4 days off therapy every week until cancer progression or intolerability.

Treatment:

Drug: LAM-002A

LAM-002A + rituximab

Experimental group

Description:

All patients will receive LAM-002A 125mg two times daily by mouth every day until cancer progression or intolerability and rituximab 375 mg/m2 by vein every week for 4 weeks and then every 8 weeks for 4 times (total of 8 infusions)

Treatment:

Drug: Rituximab

LAM-002A + atezolizumab

Experimental group

Description:

All patients will receive LAM-002A 125mg two times daily by mouth every day until cancer progression or intolerability and atezolizumab 1200 mg by vein every 3 weeks until cancer progression or intolerability

Treatment:

Drug: Atezolizumab