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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
Recruitment Status : Active, not recruiting
First Posted : November 3, 2015
Last Update Posted : August 13, 2019
Sponsor:
Information provided by (Responsible Party):
AI Therapeutics, Inc.

Study Description
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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

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 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 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Continuous monotherapy
All patients will take LAM-002A two times daily by mouth every day until cancer progression or intolerability.
 Drug: LAM-002A
25 mg capsules or 50 mg capsules
Other Name: apilimod dimesylate
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.
 Drug: LAM-002A
25 mg capsules or 50 mg capsules
Other Name: apilimod dimesylate
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)
 Drug: Rituximab
375 mg/m2 by vein
Other Name: rituxan
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
 Drug: Atezolizumab
1200 mg by vein
Other Name: Tecentriq


Outcome Measures
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Primary Outcome Measures :
  1. Determination of the MTD of oral LAM-002A [ Time Frame: 28 days ]
    Dose escalation until determination of DLTs


Secondary Outcome Measures :
  1. Peak Plasma Concentration (Cmax) of LAM-002A [ Time Frame: 28 days ]
    Evaluation of LAM-002A and its metabolites in plasma

  2. 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

  3. 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

  4. 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:
  1. 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

  2. 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

  3. Evaluation of immune modulatory effects of LAM-002A [ Time Frame: 1 cycle (28 days) to 2 cycles ]
    Determine immune modulation activity of LAM-002A

  4. Plasma identification of analytes [ Time Frame: 1 cycle (28 days) ]
    Preliminary assessment of anti-lymphoma activity


Eligibility Criteria
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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:

  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.

Contacts and Locations
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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


Locations
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United States, Alabama
Clearview Cancer Institute
Huntsville, Alabama, United States, 35805
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Georgia
Winship Cancer Institute at Emory University
Atlanta, Georgia, United States, 30322
United States, Indiana
Horizon Oncology Research, Inc.
Lafayette, Indiana, United States, 47905
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
New York University School of Medicine
New York, New York, United States, 10016
Weill Cornell Medical College
New York, New York, United States, 10021
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Virginia
Virginia Cancer Specialists
Fairfax, Virginia, United States, 22031
United States, Washington
Virginia Mason Medical Center
Seattle, Washington, United States, 98101
Sponsors and Collaborators
AI Therapeutics, Inc.
Investigators
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Study Director: Langdon Miller, MD AI Therapeutics
More Information
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Responsible Party: AI Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02594384    
Other Study ID Numbers: LAM-002A-NHL-CLN01
First Posted: November 3, 2015    Key Record Dates
Last Update Posted: August 13, 2019
Last Verified: August 2019
Keywords provided by AI Therapeutics, Inc.:
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
 Leukemia, B-Cell
Leukemia, Lymphoid
Rituximab
Atezolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents