Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic Clinical Trial
— LAM-002A/NHLOfficial 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
| Verified date | July 2023 |
| Source | AI Therapeutics, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 62 |
| Est. completion date | March 30, 2023 |
| Est. primary completion date | March 9, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | Winship Cancer Institute at Emory University | Atlanta | Georgia |
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | Virginia Cancer Specialists | Fairfax | Virginia |
| United States | University of Texas MD Anderson Cancer Center | Houston | Texas |
| United States | Clearview Cancer Institute | Huntsville | Alabama |
| United States | Mayo Clinic | Jacksonville | Florida |
| United States | Horizon Oncology Research, Inc. | Lafayette | Indiana |
| United States | New York University School of Medicine | New York | New York |
| United States | Weill Cornell Medical College | New York | New York |
| United States | Mayo Clinic | Rochester | Minnesota |
| United States | Virginia Mason Medical Center | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| AI Therapeutics, Inc. |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Microscopic changes in the internal structure of tumor cells and white blood cells | Determine the effect of LAM-002A on tumor cells and blood samples | 1 cycle (28 days) to 2 cycles | |
| Other | Evaluation of genetic alterations and expression in tumor | Determine potential genetic make-up of NHL tumors | 1 cycle (28 Days) to 2 cycles | |
| Other | Evaluation of immune modulatory effects of LAM-002A | Determine immune modulation activity of LAM-002A | 1 cycle (28 days) to 2 cycles | |
| Other | Plasma identification of analytes | Preliminary assessment of anti-lymphoma activity | 1 cycle (28 days) | |
| Primary | Determination of the MTD of oral LAM-002A | Dose escalation until determination of DLTs | 28 days | |
| Secondary | Peak Plasma Concentration (Cmax) of LAM-002A | Evaluation of LAM-002A and its metabolites in plasma | 28 days | |
| Secondary | Area under the plasma concentration versus time curve (AUC) of LAM-002A | Evaluation of LAM-002A and its metabolites in plasma | 28 days | |
| Secondary | Type and frequency of adverse events and serious adverse events as assessed by CTCAE v4.0 | Identify toxicities | 1 cycle (28 days) to 6 or more cycles | |
| Secondary | 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 | 1 cycle (28 days) to 6 or more cycles |