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CompletedNCT02594384LAM-002A/NHLUpdated Aug 22, 2024Results posted

A Phase I Dose Escalation Study of the Safety and Pharmacokinetics of LAM-002A In Patients With Non-Hodgkin's Lymphoma

A Phase 1 interventional study of LAM-002A and Rituximab in Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic, sponsored by OrphAI Therapeutics. Completed at 11 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-08-22.

Sponsored by OrphAI Therapeutics · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
62
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic

Keywords

  • Phase 1
  • Safety
  • Apilimod dimesylate
  • Pharmacokinetics
  • Non-Hodgkin Lymphoma
  • Chronic lymphocytic leukemia
03

In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 62 is above the median of 40 across 4,508 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

OrphAI Therapeutics is the lead sponsor of 4 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
62 participants (actual)

Study arms

  • Experimental
    Continuous monotherapy

    All patients will take LAM-002A two times daily by mouth every day until cancer progression or intolerability.

    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.

    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)

    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

    Drug: Atezolizumab

Interventions

  • DrugLAM-002A

    25 mg capsules or 50 mg capsules

    Also known as: apilimod dimesylate

  • DrugRituximab

    375 mg/m2 by vein

    Also known as: rituxan

  • DrugAtezolizumab

    1200 mg by vein

    Also known as: Tecentriq

06

What researchers measure

Primary outcomes

  1. Determination of the Maximum Tolerated Dose (MTD) of Continuous Oral LAM-002A

    MTD was determined by testing increasing doses up to 125 mg twice a day or 75 mg three times a day orally on dose escalation cohorts with 3 to 6 participants each. In the dose escalation, the cohort sizes of 3 to 6 subjects allow evaluation of regimen safety using a standard definition of MTD (ie, the highest starting dose associated with DLT in \<33% of subjects during the first cycle of therapy) when administered continuously (daily administration) and then when administered intermittently (repeated courses of 3 days on and 4 days off).

    Time frame: 28 days

Secondary outcomes

  1. Peak Plasma Concentration (Cmax) of LAM-002A

    Evaluation of the peak plasma concentration (Cmax) of LAM-002A and its metabolites in plasma on Day 1 and Day 8.

    Time frame: 8 days

  2. Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A

    Evaluation of the Area under the concentration-time curve from time-zero to the time of the last quantifiable concentration (AUClast) of LAM-002ALAM-002A and its metabolites in plasma on Day 1 and Day 8.

    Time frame: 8 days

  3. Objective Response Rate

    Anti-tumor response as assessed by investigator according to modified Hallek or Lugano Response Criteria by Disease Type and Cohort

    Time frame: 1 cycle (28 days) up to a maximum of 24 cycles

07

Results

Posted Aug 22, 2024
Limitations and caveats
Participants receiving LAM-002A with a regimen of 125 mg BID were accrued to both dose escalation (N=6) and then dose expansion (N=14), the results for the combined total (N=20) for this group is presented. Additionally, a MTD for the intermittent dosing regimen (3 days on and 4 days off every 7 days) was not established due to the shift of the trial to the dose expansion (monotherapy or combination therapy); the intermittent regimen was not further pursued after 3 subjects had been accrued.

Participant flow

This study was conducted at 12 study centers in the United States, 11 of which enrolled subjects to the trial.

Participant flow — Overall Study
MilestoneLAM-002A Continuous Monotherapy - 50 mg BIDLAM-002A Continuous Monotherapy - 100 mg BIDLAM-002A Continuous Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 75 mg TIDLAM-002A Intermittent Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 125 mgLAM-002A + RituximabLAM-002A + Atezolizumab
Started3854320127
Completed00000130
Not completed385431997
Withdrew: Disease progression370221255
Withdrew: Adverse event01410611
Withdrew: Withdrawal by subject00010001
Withdrew: Physician decision00000120
Withdrew: Progressive leukocytosis00100000
Withdrew: Lack of efficacy00001000
Withdrew: Substantial noncompliance00000010

Outcome measures

PrimaryDetermination of the Maximum Tolerated Dose (MTD) of Continuous Oral LAM-002A

MTD was determined by testing increasing doses up to 125 mg twice a day or 75 mg three times a day orally on dose escalation cohorts with 3 to 6 participants each. In the dose escalation, the cohort sizes of 3 to 6 subjects allow evaluation of regimen safety using a standard definition of MTD (ie, the highest starting dose associated with DLT in \<33% of subjects during the first cycle of therapy) when administered continuously (daily administration) and then when administered intermittently (repeated courses of 3 days on and 4 days off).

Time frame:
28 days
Reported as:
Number · mg BID
Determination of the Maximum Tolerated Dose (MTD) of Continuous Oral LAM-002A
mg BIDAll Participants
Determination of the Maximum Tolerated Dose (MTD) of Continuous Oral LAM-002A125
SecondaryPeak Plasma Concentration (Cmax) of LAM-002A

Evaluation of the peak plasma concentration (Cmax) of LAM-002A and its metabolites in plasma on Day 1 and Day 8.

Time frame:
8 days
Reported as:
Mean · ng/mL
Peak Plasma Concentration (Cmax) of LAM-002A
ng/mLLAM-002A Continuous Monotherapy - 50 mg BIDLAM-002A Continuous Monotherapy - 75 mg TIDLAM-002A Continuous Monotherapy - 100 mg BIDLAM-002A Continuous Monotherapy - 125 mg BIDLAM-002A Continuous Monotherapy - 150 mg BIDLAM-002A Intermittent Monotherapy - 150 mg
Apilimod - Day 1117 ± 69.6158 ± 61.6263 ± 168207 ± 82.4243 ± 76.1280 ± 135
Apilimod - Day 8140 ± 95.1339 ± 215331 ± 273331 ± 287369 ± 90.5108
STA-5908 - Day 1112 ± 85.0114 ± 71.6215 ± 88.6144 ± 92.5196 ± 142207 ± 135
STA-5908 - Day 8103 ± 43.7239 ± 195278 ± 137234 ± 173240 ± 99.7113
STA-5944 - Day 1209 ± 145243 ± 124346 ± 131281 ± 125369 ± 306466 ± 247
STA-5944 - Day 8188 ± 101436 ± 334439 ± 215383 ± 225391 ± 9.90260
STA-6048 - Day 163.2 ± 40.259.9 ± 54.0136 ± 64.290.0 ± 58.6131 ± 134145 ± 66.0
STA-6048 - Day 860.6 ± 32.0154 ± 113161 ± 43.0122 ± 81.7116 ± 87.4140
SecondaryArea Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A

Evaluation of the Area under the concentration-time curve from time-zero to the time of the last quantifiable concentration (AUClast) of LAM-002ALAM-002A and its metabolites in plasma on Day 1 and Day 8.

Time frame:
8 days
Reported as:
Mean · h*ng/mL
Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A
h*ng/mLLAM-002A Continuous Monotherapy - 50 mg BIDLAM-002A Continuous Monotherapy - 75 mg TIDLAM-002A Continuous Monotherapy - 100 mg BIDLAM-002A Continuous Monotherapy - 125 mg BIDLAM-002A Continuous Monotherapy - 150 mg BIDLAM-002A Intermittent Monotherapy - 150 mg BID
Apilimod - Day 1238 ± 88.1583 ± 290515 ± 221562 ± 234700 ± 290777 ± 437
Apilimod - Day 8374 ± 1191040 ± 4831130 ± 9301290 ± 10401060 ± 85.7563
STA-5944 - Day 1542 ± 2141020 ± 6591120 ± 5501180 ± 5871590 ± 14201700 ± 843
STA-5944 - Day 8653 ± 3652070 ± 14301810 ± 12401860 ± 11601320 ± 2111350
STA-5908 - Day 1312 ± 156526 ± 291762 ± 371625 ± 419936 ± 734968 ± 547
STA-5908 - Day 8433 ± 1951140 ± 8181360 ± 7961270 ± 8751040 ± 572690
STA-6048 - Day 1238 ± 91.2280 ± 216622 ± 372443 ± 325785 ± 923869 ± 415
STA-6048 - Day 8308 ± 1641040 ± 780959 ± 343746 ± 509556 ± 397760
SecondaryObjective Response Rate

Anti-tumor response as assessed by investigator according to modified Hallek or Lugano Response Criteria by Disease Type and Cohort

Time frame:
1 cycle (28 days) up to a maximum of 24 cycles
Reported as:
Count of participants · Participants
Objective Response Rate
ParticipantsLAM-002A Continuous Monotherapy - 50 mg BIDLAM-002A Continuous Monotherapy - 100 mg BIDLAM-002A Continuous Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 75 mg TIDLAM-002A Intermittent Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 125 mgLAM-002A + RituximabLAM-002A + Atezolizumab
DLBCL (diffuse large B-cell lymphoma)00000000
FL (follicular lymphoma)00000252
MZL (marginal zone lymphoma)00000010
MCL (mantle cell lymphoma)00000000
CLL/SLL (chronic lymphocytic leukemia/ small lymphocytic lymphoma)00000000

Adverse events

Collected over Adverse Events will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0. AEs, including SAEs, were captured from Cycle 1 Day 1 through 30 days after the last dose of study treatment, an average of 4.5 months.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
LAM-002A Continuous Monotherapy - 50 mg BID0/3 (0%)0/3 (0%)3/3 (100%)
LAM-002A Continuous Monotherapy - 100 mg BID1/8 (12.5%)3/8 (37.5%)8/8 (100%)
LAM-002A Continuous Monotherapy - 150 mg BID1/5 (20%)1/5 (20%)5/5 (100%)
LAM-002A Continuous Monotherapy - 75 mg TID0/4 (0%)2/4 (50%)4/4 (100%)
LAM-002A Intermittent Monotherapy - 150 mg BID0/3 (0%)0/3 (0%)3/3 (100%)
LAM-002A Continuous Monotherapy - 125 mg BID3/20 (15%)9/20 (45%)20/20 (100%)
LAM-002A + Rituximab0/12 (0%)5/12 (41.7%)12/12 (100%)
LAM-002A + Atezolizumab3/7 (42.9%)6/7 (85.7%)7/7 (100%)
Most frequent serious events
Showing 10 of 33
Most frequent serious events
EventLAM-002A Continuous Monotherapy - 50 mg BIDLAM-002A Continuous Monotherapy - 100 mg BIDLAM-002A Continuous Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 75 mg TIDLAM-002A Intermittent Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 125 mg BIDLAM-002A + RituximabLAM-002A + Atezolizumab
Febrile neutropeniaBlood and lymphatic system disorders0/31/80/51/40/30/200/121/7
Hodgkin's diseaseNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/30/80/51/40/30/200/120/7
SyncopeNervous system disorders0/30/80/51/40/30/200/120/7
HypoxiaRespiratory, thoracic and mediastinal disorders0/30/80/51/40/30/200/120/7
HypotensionVascular disorders0/30/80/51/40/30/200/120/7
Lung infectionRespiratory, thoracic and mediastinal disorders0/30/81/50/40/30/200/120/7
Tumour lysis syndromeMetabolism and nutrition disorders0/30/80/50/40/30/202/120/7
ColitisGastrointestinal disorders0/30/80/50/40/30/200/121/7
NauseaGastrointestinal disorders0/30/80/50/40/30/200/121/7
Disease progressionGeneral disorders0/31/80/50/40/31/200/121/7
Most frequent other events
Showing 10 of 228
Most frequent other events
EventLAM-002A Continuous Monotherapy - 50 mg BIDLAM-002A Continuous Monotherapy - 100 mg BIDLAM-002A Continuous Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 75 mg TIDLAM-002A Intermittent Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 125 mg BIDLAM-002A + RituximabLAM-002A + Atezolizumab
NauseaGastrointestinal disorders0/33/83/53/40/39/206/126/7
VomitingGastrointestinal disorders0/31/83/53/40/34/203/124/7
ConstipationGastrointestinal disorders0/32/80/52/41/33/201/125/7
DiarrhoeaGastrointestinal disorders1/30/82/52/42/36/206/121/7
InsomniaPsychiatric disorders0/31/82/51/42/31/200/122/7
Electrocardiogram QT prolongedInvestigations0/30/83/51/40/30/200/120/7
FatigueGeneral disorders0/34/82/52/41/310/207/121/7
Oedema peripheralGeneral disorders1/31/80/52/40/33/202/121/7
Hemoglobin decreasedInvestigations0/33/80/52/40/35/200/121/7
Blood creatinine increasedInvestigations0/30/81/52/40/32/201/121/7

Baseline characteristics

Full analysis set=All subjects who received ≥1 dose of study drug.

Age, Customized
Age, Customized(Participants)LAM-002A Continuous Monotherapy - 50 mg BIDLAM-002A Continuous Monotherapy - 100 mg BIDLAM-002A Continuous Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 75 mg TIDLAM-002A Intermittent Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 125 mgLAM-002A + RituximabLAM-002A + AtezolizumabTotal
Age Category — <65 years2310097224
Age Category — ≥65 years15443115538
Sex: Female, Male
Sex: Female, Male(Participants)LAM-002A Continuous Monotherapy - 50 mg BIDLAM-002A Continuous Monotherapy - 100 mg BIDLAM-002A Continuous Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 75 mg TIDLAM-002A Intermittent Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 125 mgLAM-002A + RituximabLAM-002A + AtezolizumabTotal
Female1542294330
Male23121118432
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)LAM-002A Continuous Monotherapy - 50 mg BIDLAM-002A Continuous Monotherapy - 100 mg BIDLAM-002A Continuous Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 75 mg TIDLAM-002A Intermittent Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 125 mgLAM-002A + RituximabLAM-002A + AtezolizumabTotal
Race — White364331611753
Race — Black/African American010101104
Race — Other011003005
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)LAM-002A Continuous Monotherapy - 50 mg BIDLAM-002A Continuous Monotherapy - 100 mg BIDLAM-002A Continuous Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 75 mg TIDLAM-002A Intermittent Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 125 mgLAM-002A + RituximabLAM-002A + AtezolizumabTotal
Ethnicity — Not Hispanic/Latino385331612757
Ethnicity — Hispanic/Latino000104005
Eastern Cooperative Oncology Group (ECOG) Performance Status
Eastern Cooperative Oncology Group (ECOG) Performance Status(Participants)LAM-002A Continuous Monotherapy - 50 mg BIDLAM-002A Continuous Monotherapy - 100 mg BIDLAM-002A Continuous Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 75 mg TIDLAM-002A Intermittent Monotherapy - 150 mg BIDLAM-002A Continuous Monotherapy - 125 mgLAM-002A + RituximabLAM-002A + AtezolizumabTotal
0, fully active, able to carry on all predisease performance without restrictions0511173018
1, restricted in physically strenuous activity but ambulatory and able to do light or sedentary work33322119639
2, ambulatory and capable of all self-care but unable to work. Up more than 50% of waking hours001102004
3, capable of only limited self-care, confined to bed or chair more than 50% of waking hours000000011
08

Study locations

11 sites
  • Clearview Cancer Institute
    Huntsville, Alabama 35805, United States
  • Mayo Clinic
    Jacksonville, Florida 32224, United States
  • Winship Cancer Institute at Emory University
    Atlanta, Georgia 30322, United States
  • Horizon Oncology Research, Inc.
    Lafayette, Indiana 47905, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
  • New York University School of Medicine
    New York, New York 10016, United States
  • Weill Cornell Medical College
    New York, New York 10021, United States
  • University of Texas MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • Virginia Cancer Specialists
    Fairfax, Virginia 22031, United States
  • Virginia Mason Medical Center
    Seattle, Washington 98101, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Feb 18, 2020

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 22, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02594384
Lead sponsor
OrphAI Therapeutics
Responsible party
Sponsor
First posted
Nov 3, 2015
Start date
Oct 2015
Primary completion
Mar 9, 2020
Completion
Mar 30, 2023
Results posted
Aug 22, 2024
Last update
Aug 22, 2024

Study contacts

Langdon Miller, MD
study director · AI Therapeutics

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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