A 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)
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| ClinicalTrials.gov Identifier: NCT02594384 |
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Recruitment Status :
Recruiting
First Posted : November 3, 2015
Last Update Posted : January 10, 2019
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Sponsor:
AI Therapeutics, Inc (formerly known as LAM Therapeutics, Inc.)
Information provided by (Responsible Party):
AI Therapeutics, Inc (formerly known as LAM Therapeutics, Inc.)
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic | Drug: LAM-002A Drug: Rituximab Drug: Atezolizumab | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 75 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 Start Date : | October 2015 |
| Estimated Primary Completion Date : | May 2019 |
| Estimated Study Completion Date : | December 2019 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Lymphoma
| Arm | Intervention/treatment |
|---|---|
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Experimental: Continuous monotherapy
All patients will take LAM-002A two times daily by mouth every day until cancer progression or intolerability.
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Drug: LAM-002A
25 mg capsules or 50 mg capsules
Other Name: apilimod dimesylate |
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Experimental: Intermittent monotherapy
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.
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Drug: LAM-002A
25 mg capsules or 50 mg capsules
Other Name: apilimod dimesylate |
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Experimental: LAM-002A + rituximab
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)
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Drug: Rituximab
375 mg/m2 by vein
Other Name: rituxan |
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Experimental: LAM-002A + atezolizumab
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
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Drug: Atezolizumab
1200 mg by vein
Other Name: Tecentriq |
Primary Outcome Measures :
- Determination of the MTD of oral LAM-002A [ Time Frame: 28 days ]Dose escalation until determination of DLTs
Secondary Outcome Measures :
- Peak Plasma Concentration (Cmax) of LAM-002A [ Time Frame: 28 days ]Evaluation of LAM-002A and its metabolites in plasma
- Area under the plasma concentration versus time curve (AUC) of LAM-002A [ Time Frame: 28 days ]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 [ Time Frame: 1 cycle (28 days) to 6 or more cycles ]Identify toxicities
- Anti-tumor response as assessed by investigator according to modified Hallek or Lugano Response Criteria [ Time Frame: 1 cycle (28 days) to 6 or more cycles ]Evaluation of the ability of LAM-002A to shrink tumors
Other Outcome Measures:
- Microscopic changes in the internal structure of tumor cells and white blood cells [ Time Frame: 1 cycle (28 days) to 2 cycles ]Determine the effect of LAM-002A on tumor cells and blood samples
- Evaluation of genetic alterations and expression in tumor [ Time Frame: 1 cycle (28 Days) to 2 cycles ]Determine potential genetic make-up of NHL tumors
- Evaluation of immune modulatory effects of LAM-002A [ Time Frame: 1 cycle (28 days) to 2 cycles ]Determine immune modulation activity of LAM-002A
- Plasma identification of analytes [ Time Frame: 1 cycle (28 days) ]Preliminary assessment of anti-lymphoma activity
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02594384
Contacts
| Contact: Henri Lichenstein, PhD | 2034587100 ext 318 | hlichens@ai-thera.com |
Locations
| United States, Alabama | |
| Clearview Cancer Institute | Recruiting |
| Huntsville, Alabama, United States, 35805 | |
| Contact: Avitra Bone, RN 256-705-4283 studycoordinator@ccihsv.com | |
| Principal Investigator: Marshall Schreeder, MD | |
| United States, Florida | |
| Mayo Clinic | Recruiting |
| Jacksonville, Florida, United States, 32224 | |
| Contact: Kathleen Burke, RN 904-953-7563 burke.kathleen@mayo.com | |
| Principal Investigator: Taimur Sher, MD | |
| United States, Georgia | |
| Winship Cancer Institute at Emory University | Recruiting |
| Atlanta, Georgia, United States, 30322 | |
| Contact: Kaylan Dixon 404-778-4449 kaylan.dixon@emory.edu | |
| Principal Investigator: Jonathan Cohen, MD | |
| United States, Indiana | |
| Horizon Oncology Research, Inc. | Recruiting |
| Lafayette, Indiana, United States, 47905 | |
| Contact: Wael A Harb, MD 765-446-5111 wharb@horizonbioadvance.com | |
| Principal Investigator: Wael A Harb, MD | |
| United States, Massachusetts | |
| Massachusetts General Hospital | Recruiting |
| Boston, Massachusetts, United States, 02114 | |
| Contact: Lauren Ramos 617-643-9607 lramos7@mgh.harvard.edu | |
| Principal Investigator: Jeremy Abramson, MD | |
| United States, Minnesota | |
| Mayo Clinic | Recruiting |
| Rochester, Minnesota, United States, 55905 | |
| Contact: Corinne Parker 507-266-3784 parker.corinne@mayo.edu | |
| Principal Investigator: Stephen Ansell, MD | |
| United States, New York | |
| New York University School of Medicine | Recruiting |
| New York, New York, United States, 10016 | |
| Contact: Ion Marinescu 646-501-7920 Ion.Marinescu@nyumc.org | |
| Principal Investigator: Catherine Diefenbach, MD | |
| Weill Cornell Medical College | Recruiting |
| New York, New York, United States, 10021 | |
| Contact: Arianna Goldberg 646-962-8232 Arg2016@med.cornell.edu | |
| Principal Investigator: Sarah Rutherford, MD | |
| United States, Texas | |
| University of Texas MD Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Linda Claret 713-792-1044 lcclaret@mdanderson.org | |
| Principal Investigator: Loretta Nastoupil, MD | |
| United States, Virginia | |
| Virginia Cancer Specialists | Recruiting |
| Fairfax, Virginia, United States, 22031 | |
| Contact: VCS Phase 1 Team 703-208-3192 Karin.Choquette@usoncology.com | |
| Principal Investigator: Dipti Patel-Donnelly, MD | |
| United States, Washington | |
| Virginia Mason Medical Center | Recruiting |
| Seattle, Washington, United States, 98101 | |
| Contact: Anas Najjar 206-287-5671 Anas.Najjar@virginiamason.org | |
| Principal Investigator: David Aboulafia, MD | |
Sponsors and Collaborators
AI Therapeutics, Inc (formerly known as LAM Therapeutics, Inc.)
Investigators
| Study Director: | Langdon Miller, MD | AI Therapeutics |
| Responsible Party: | AI Therapeutics, Inc (formerly known as LAM Therapeutics, Inc.) |
| ClinicalTrials.gov Identifier: | NCT02594384 History of Changes |
| Other Study ID Numbers: |
LAM-002A-NHL-CLN01 |
| First Posted: | November 3, 2015 Key Record Dates |
| Last Update Posted: | January 10, 2019 |
| Last Verified: | January 2019 |
Keywords provided by AI Therapeutics, Inc (formerly known as LAM Therapeutics, Inc.):
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Phase 1 Safety Apilimod dimesylate |
Pharmacokinetics Non-Hodgkin Lymphoma Chronic lymphocytic leukemia |
Additional relevant MeSH terms:
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Lymphoma Lymphoma, Non-Hodgkin Leukemia, Lymphocytic, Chronic, B-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Leukemia, B-Cell |
Leukemia, Lymphoid Leukemia Atezolizumab Rituximab Antibodies, Monoclonal Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |