Back to resultsA Phase I Dose Escalation Study of the Safety and Pharmacokinetics of LAM-002A In Patients With Non-Hodgkin's Lymphoma (LAM-002A/NHL) (LAM-002A/NHL)
Primary Purpose
Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
LAM-002A
Rituximab
Atezolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic focused on measuring Phase 1, Safety, Apilimod dimesylate, Pharmacokinetics, Non-Hodgkin Lymphoma, Chronic lymphocytic leukemia
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- Clearview Cancer Institute
- Mayo Clinic
- Winship Cancer Institute at Emory University
- Horizon Oncology Research, Inc.
- Massachusetts General Hospital
- Mayo Clinic
- New York University School of Medicine
- Weill Cornell Medical College
- University of Texas MD Anderson Cancer Center
- Virginia Cancer Specialists
- Virginia Mason Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Continuous monotherapy
Intermittent monotherapy
LAM-002A + rituximab
LAM-002A + atezolizumab
Arm Description
All patients will take LAM-002A two times daily by mouth every day until cancer progression or intolerability.
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.
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)
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
Outcomes
Primary Outcome Measures
Determination of the MTD of oral LAM-002A
Dose escalation until determination of DLTs
Secondary Outcome Measures
Peak Plasma Concentration (Cmax) of LAM-002A
Evaluation of LAM-002A and its metabolites in plasma
Area under the plasma concentration versus time curve (AUC) of LAM-002A
Evaluation of LAM-002A and its metabolites in plasma
Type and frequency of adverse events and serious adverse events as assessed by CTCAE v4.0
Identify toxicities
Anti-tumor response as assessed by investigator according to modified Hallek or Lugano Response Criteria
Evaluation of the ability of LAM-002A to shrink tumors
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02594384
Brief Title
A Phase I Dose Escalation Study of the Safety and Pharmacokinetics of LAM-002A In Patients With Non-Hodgkin's Lymphoma (LAM-002A/NHL)
Acronym
LAM-002A/NHL
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
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
October 2015 (undefined)
Primary Completion Date
March 9, 2020 (Actual)
Study Completion Date
March 30, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
OrphAI Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic
Keywords
Phase 1, Safety, Apilimod dimesylate, Pharmacokinetics, Non-Hodgkin Lymphoma, Chronic lymphocytic leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
62 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Continuous monotherapy
Arm Type
Experimental
Arm Description
All patients will take LAM-002A two times daily by mouth every day until cancer progression or intolerability.
Arm Title
Intermittent monotherapy
Arm Type
Experimental
Arm 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.
Arm Title
LAM-002A + rituximab
Arm Type
Experimental
Arm 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)
Arm Title
LAM-002A + atezolizumab
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
LAM-002A
Other Intervention Name(s)
apilimod dimesylate
Intervention Description
25 mg capsules or 50 mg capsules
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
rituxan
Intervention Description
375 mg/m2 by vein
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
Tecentriq
Intervention Description
1200 mg by vein
Primary Outcome Measure Information:
Title
Determination of the MTD of oral LAM-002A
Description
Dose escalation until determination of DLTs
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Peak Plasma Concentration (Cmax) of LAM-002A
Description
Evaluation of LAM-002A and its metabolites in plasma
Time Frame
28 days
Title
Area under the plasma concentration versus time curve (AUC) of LAM-002A
Description
Evaluation of LAM-002A and its metabolites in plasma
Time Frame
28 days
Title
Type and frequency of adverse events and serious adverse events as assessed by CTCAE v4.0
Description
Identify toxicities
Time Frame
1 cycle (28 days) to 6 or more cycles
Title
Anti-tumor response as assessed by investigator according to modified Hallek or Lugano Response Criteria
Description
Evaluation of the ability of LAM-002A to shrink tumors
Time Frame
1 cycle (28 days) to 6 or more cycles
Other Pre-specified Outcome Measures:
Title
Microscopic changes in the internal structure of tumor cells and white blood cells
Description
Determine the effect of LAM-002A on tumor cells and blood samples
Time Frame
1 cycle (28 days) to 2 cycles
Title
Evaluation of genetic alterations and expression in tumor
Description
Determine potential genetic make-up of NHL tumors
Time Frame
1 cycle (28 Days) to 2 cycles
Title
Evaluation of immune modulatory effects of LAM-002A
Description
Determine immune modulation activity of LAM-002A
Time Frame
1 cycle (28 days) to 2 cycles
Title
Plasma identification of analytes
Description
Preliminary assessment of anti-lymphoma activity
Time Frame
1 cycle (28 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Langdon Miller, MD
Organizational Affiliation
AI Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Clearview Cancer Institute
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35805
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Winship Cancer Institute at Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Horizon Oncology Research, Inc.
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47905
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
New York University School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Virginia Cancer Specialists
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Virginia Mason Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Phase I Dose Escalation Study of the Safety and Pharmacokinetics of LAM-002A In Patients With Non-Hodgkin's Lymphoma (LAM-002A/NHL)
We'll reach out to this number within 24 hrs