A Phase I Dose Escalation Study of the Safety and Pharmacokinetics of LAM-002A In Patients With Non-Hodgkin's Lymphoma
LAM-002A/NHL
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
1 other identifier
interventional
62
1 country
11
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2015
Longer than P75 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2015
CompletedFirst Submitted
Initial submission to the registry
October 29, 2015
CompletedFirst Posted
Study publicly available on registry
November 3, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 9, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
March 30, 2023
CompletedResults Posted
Study results publicly available
August 22, 2024
CompletedAugust 22, 2024
August 1, 2024
4.4 years
October 29, 2015
March 4, 2024
August 19, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Determination of the Maximum Tolerated Dose (MTD) of Continuous Oral LAM-002A
MTD was determined by testing increasing doses up to 125 mg twice a day or 75 mg three times a day orally on dose escalation cohorts with 3 to 6 participants each. In the dose escalation, the cohort sizes of 3 to 6 subjects allow evaluation of regimen safety using a standard definition of MTD (ie, the highest starting dose associated with DLT in \<33% of subjects during the first cycle of therapy) when administered continuously (daily administration) and then when administered intermittently (repeated courses of 3 days on and 4 days off).
28 days
Secondary Outcomes (3)
Peak Plasma Concentration (Cmax) of LAM-002A
8 days
Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A
8 days
Objective Response Rate
1 cycle (28 days) up to a maximum of 24 cycles
Study Arms (4)
Continuous monotherapy
EXPERIMENTALAll patients will take LAM-002A two times daily by mouth every day until cancer progression or intolerability.
Intermittent monotherapy
EXPERIMENTALAll 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.
LAM-002A + rituximab
EXPERIMENTALAll 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)
LAM-002A + atezolizumab
EXPERIMENTALAll 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
Interventions
25 mg capsules or 50 mg capsules
Eligibility Criteria
You may qualify if:
- Able to understand and comply with the protocol requirements and has signed the informed consent document.
- 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.
- 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
- 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)
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or less.
- Adequate organ and marrow function.
- Able to swallow oral capsules without difficulty.
- Acceptable birth control.
- Women of childbearing potential : negative pregnancy test
- Adequate archival or fresh tumor tissue (from biopsy, bone marrow, or peripheral blood) for analysis of potential predictive biomarkers.
You may not qualify if:
- 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.
- Not recovered from toxicity due to all prior therapies.
- Other uncontrolled significant illness.
- History of malabsorption or other gastrointestinal (GI) disease that may significantly alter the absorption of LAM-002A
- Major surgery within 28 days prior to first dose of study drug.
- Past history of tuberculosis (TB) or active infection with TB, human immunodeficiency virus (HIV), hepatitis B or hepatitis C.
- Lactation or breast feeding.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
Clearview Cancer Institute
Huntsville, Alabama, 35805, United States
Mayo Clinic
Jacksonville, Florida, 32224, United States
Winship Cancer Institute at Emory University
Atlanta, Georgia, 30322, United States
Horizon Oncology Research, Inc.
Lafayette, Indiana, 47905, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
New York University School of Medicine
New York, New York, 10016, United States
Weill Cornell Medical College
New York, New York, 10021, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Virginia Cancer Specialists
Fairfax, Virginia, 22031, United States
Virginia Mason Medical Center
Seattle, Washington, 98101, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Participants receiving LAM-002A with a regimen of 125 mg BID were accrued to both dose escalation (N=6) and then dose expansion (N=14), the results for the combined total (N=20) for this group is presented. Additionally, a MTD for the intermittent dosing regimen (3 days on and 4 days off every 7 days) was not established due to the shift of the trial to the dose expansion (monotherapy or combination therapy); the intermittent regimen was not further pursued after 3 subjects had been accrued.
Results Point of Contact
- Title
- Esther Nkrumah
- Organization
- OrphAI Therapeutics
Study Officials
- STUDY DIRECTOR
Langdon Miller, MD
AI Therapeutics
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 29, 2015
First Posted
November 3, 2015
Study Start
October 1, 2015
Primary Completion
March 9, 2020
Study Completion
March 30, 2023
Last Updated
August 22, 2024
Results First Posted
August 22, 2024
Record last verified: 2024-08