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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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.

Tracking Information
First Submitted Date  ICMJE October 29, 2015
First Posted Date  ICMJE November 3, 2015
Last Update Posted Date August 13, 2019
Study Start Date  ICMJE October 2015
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 7, 2018)
Determination of the MTD of oral LAM-002A [ Time Frame: 28 days ]
Dose escalation until determination of DLTs
Original Primary Outcome Measures  ICMJE
 (submitted: October 30, 2015)
Determination of the MTD of oral LAM-002A [ Time Frame: 28 days ]
Dose escalation until determination of dose limiting toxicities
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2018)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2015)
  • 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
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 1 cycle (28 days) to 6 or more cycles ]
    Identify toxicities
  • Evaluate primary anti-tumor activity [ Time Frame: 1 cycle (28 days) to 6 or more cycles ]
    evaluate the ability of LAM-002A to shrink tumors
Current Other Pre-specified Outcome Measures
 (submitted: October 30, 2015)
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Phase I Dose Escalation Study of the Safety and Pharmacokinetics of LAM-002A In Patients With Non-Hodgkin's Lymphoma (LAM-002A/NHL)
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic
Intervention  ICMJE
  • Drug: LAM-002A
    25 mg capsules or 50 mg capsules
    Other Name: apilimod dimesylate
  • Drug: Rituximab
    375 mg/m2 by vein
    Other Name: rituxan
  • Drug: Atezolizumab
    1200 mg by vein
    Other Name: Tecentriq
Study Arms  ICMJE
  • Experimental: Continuous monotherapy
    All patients will take LAM-002A two times daily by mouth every day until cancer progression or intolerability.
    Intervention: Drug: LAM-002A
  • 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.
    Intervention: Drug: LAM-002A
  • 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)
    Intervention: Drug: Rituximab
  • 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
    Intervention: Drug: Atezolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 12, 2019)
62
Original Estimated Enrollment  ICMJE
 (submitted: October 30, 2015)
75
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02594384
Other Study ID Numbers  ICMJE LAM-002A-NHL-CLN01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AI Therapeutics, Inc.
Study Sponsor  ICMJE AI Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Langdon Miller, MD AI Therapeutics
PRS Account AI Therapeutics, Inc.
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP