Lymphoma, Non-Hodgkin; Leukemia, Chronic LymphocyticPhase 1LAM-002A/NHLNCT02594384

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

A Phase 1 study testing LAM-002A, Rituximab and Atezolizumab in people with Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic, run by IRulya Therapeutics Inc. at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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 more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic
What is being tested?: LAM-002A, Rituximab and Atezolizumab
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 62 participants
Where: 11 sitesUnited States
Study dates: Oct 2015to 30 Mar 2023
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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.

Who cannot join

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.

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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.

Trial locations and contacts

11 sites in 1 country.

City, postcode or hospital

11 sites in 1 country

United States11 sites

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

Other trials in United States

About this study

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

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.

Conditions: Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic
Being tested: LAM-002A, Rituximab, Atezolizumab
Keywords: Phase 1, Safety, Apilimod dimesylate, Pharmacokinetics, Non-Hodgkin Lymphoma, Chronic lymphocytic leukemia
Medical subject headings: Lymphoma, Leukemia, Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LAM-002ADrug
Also called apilimod dimesylate
25 mg capsules or 50 mg capsules
RituximabDrug
Also called rituxan
375 mg/m2 by vein
AtezolizumabDrug
Also called Tecentriq
1200 mg by vein

Study groups in NCT02594384
Study group	Role	What they receive
Continuous monotherapy	Experimental	All patients will take LAM-002A two times daily by mouth every day until cancer progression or intolerability. Receives: Drug: LAM-002A
Intermittent monotherapy	Experimental	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. Receives: Drug: LAM-002A
LAM-002A + rituximab	Experimental	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) Receives: Drug: Rituximab
LAM-002A + atezolizumab	Experimental	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 Receives: Drug: Atezolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 28 days

Secondary outcomes (3)

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.
Measured: 8 days
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.
Measured: 8 days
Objective Response Rate
Anti-tumor response as assessed by investigator according to modified Hallek or Lugano Response Criteria by Disease Type and Cohort
Measured: 1 cycle (28 days) up to a maximum of 24 cycles

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 201530 Mar 2023

First posted3 Nov 2015 (estimated)
Study startOct 2015
Primary completion9 Mar 2020
Study completion30 Mar 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Lymphoma, Non-Hodgkin; Leukemia, Chronic LymphocyticStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 62 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02594384
Sponsor's protocol ID: LAM-002A-NHL-CLN01
Acronym: LAM-002A/NHL
Status last verified: Aug 2024
First submitted: 29 Oct 2015
Last updated: 22 Aug 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma
Active, not recruitingPhase 1
A Rollover Study of CC-122
Non-Hodgkin Lymphoma
Enrolling by invitationPhase 1
A Rollover Study for Continued Study Treatment and Ongoing Safety Monitoring
Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Chronic, B-Cell
Active, not recruitingPhase 1/2
First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma
DLBCL, High-grade B-cell Lymphoma (HGBCL)
Active, not recruitingPhase 1/2
Trial of the Safety and Efficacy of Epcoritamab in Japanese Subjects With Relapsed or Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (R/R B-NHL)
Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma

All Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02594384
Acronym / sponsor ID: LAM-002A/NHL / LAM-002A-NHL-CLN01
Conditions: Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic
Keywords: Phase 1, Safety, Apilimod dimesylate, Pharmacokinetics, Non-Hodgkin Lymphoma, Chronic lymphocytic leukemia
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 62 participants (actual)
Lead sponsor: IRulya Therapeutics Inc.Industry (pharma, biotech, devices)
Study start: Oct 2015
Primary completion: 9 Mar 2020 (actual)
Study completion: 30 Mar 2023 (actual)
First posted: 3 Nov 2015 (estimated)
Results: Posted 22 Aug 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Continuous monotherapy	Experimental	Drug: LAM-002AAll patients will take LAM-002A two times daily by mouth every day until cancer progression or intolerability.
Intermittent monotherapy	Experimental	Drug: LAM-002AAll 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.
LAM-002A + rituximab	Experimental	Drug: RituximabAll 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)
LAM-002A + atezolizumab	Experimental	Drug: AtezolizumabAll 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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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.

Key exclusion criteria (9 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LAM-002AAlso: apilimod dimesylate25 mg capsules or 50 mg capsules	Drug	Continuous monotherapy, Intermittent monotherapy
RituximabAlso: rituxan375 mg/m2 by vein	Drug	LAM-002A + rituximab
AtezolizumabAlso: Tecentriq1200 mg by vein	Drug	LAM-002A + atezolizumab

Primary outcome

Determination of the Maximum Tolerated Dose (MTD) of Continuous Oral LAM-002A
Time frame: 28 days
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).

3 secondary outcomes

Peak Plasma Concentration (Cmax) of LAM-002A
Time frame: 8 days
Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A
Time frame: 8 days
Objective Response Rate
Time frame: 1 cycle (28 days) up to a maximum of 24 cycles

Results and safety

Results posted to the registry on 22 Aug 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
LAM-002A Continuous Monotherapy - 50 mg BID	3	0
LAM-002A Continuous Monotherapy - 100 mg BID	8	0
LAM-002A Continuous Monotherapy - 150 mg BID	5	0
LAM-002A Continuous Monotherapy - 75 mg TID	4	0
LAM-002A Intermittent Monotherapy - 150 mg BID	3	0
LAM-002A Continuous Monotherapy - 125 mg	20	1
LAM-002A + Rituximab	12	3
LAM-002A + Atezolizumab	7	0

Primary outcome: Determination of the Maximum Tolerated Dose (MTD) of Continuous Oral LAM-002A

Time frame: 28 days. Number. Unit: mg BID

Measure	All Participants n = 40
Value	125

Population analysed: Full analysis set=All subjects who receive ≥1 dose of study drug.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
LAM-002A Continuous Monotherapy - 50 mg BID	0 of 3 (0%)	3 of 3 (100%)	0 of 3
LAM-002A Continuous Monotherapy - 100 mg BID	3 of 8 (37.5%)	8 of 8 (100%)	1 of 8
LAM-002A Continuous Monotherapy - 150 mg BID	1 of 5 (20%)	5 of 5 (100%)	1 of 5
LAM-002A Continuous Monotherapy - 75 mg TID	2 of 4 (50%)	4 of 4 (100%)	0 of 4
LAM-002A Intermittent Monotherapy - 150 mg BID	0 of 3 (0%)	3 of 3 (100%)	0 of 3
LAM-002A Continuous Monotherapy - 125 mg BID	9 of 20 (45%)	20 of 20 (100%)	3 of 20
LAM-002A + Rituximab	5 of 12 (41.7%)	12 of 12 (100%)	0 of 12
LAM-002A + Atezolizumab	6 of 7 (85.7%)	7 of 7 (100%)	3 of 7

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic

RecruitingObservational study
Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma
Active, not recruitingPhase 1
A Rollover Study of CC-122
Non-Hodgkin Lymphoma
Enrolling by invitationPhase 1
A Rollover Study for Continued Study Treatment and Ongoing Safety Monitoring
Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Chronic, B-Cell
Active, not recruitingPhase 1/2
First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma
DLBCL, High-grade B-cell Lymphoma (HGBCL)
Active, not recruitingPhase 1/2
Trial of the Safety and Efficacy of Epcoritamab in Japanese Subjects With Relapsed or Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (R/R B-NHL)
Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Langdon Miller, MD study director

AI Therapeutics

11 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LAM-002A, Rituximab and Atezolizumab in people with Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic, run by IRulya Therapeutics Inc. at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determination of the Maximum Tolerated Dose (MTD) of Continuous Oral LAM-002A (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02594384.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2024.