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Chronic Lymphocytic Leukemia (CLL)Phase 1NCT02914938

A Study of ME-401 in Subjects With CLL/SLL, FL, and B-cell Non Hodgkin's Lymphoma

A Phase 1 study testing ME-401, Rituximab and Zanubrutinib in people with Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL), run by MEI Pharma, Inc. at 24 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

A Three-Arm Study of ME-401 in Subjects with Relapsed/Refractory CLL/SLL or FL, of ME-401 in Combination with Rituximab in Subjects with Relapsed/Refractory CLL/SLL or B-cell NHL, and of ME-401 in Combination with Zanubrutinib in Subjects with Relapsed/Refractory CLL/SLL or B-cell NHL Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ME-401, Rituximab and Zanubrutinib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
97 participants
Where
24 sitesin 2 countries
Study dates
Oct 2016to 29 Mar 2023
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Diagnosis of relapsed/refractory CLL and/or relapsed/refractory SLL or FL
  • No prior therapy with PI3Kd inhibitors
  • No prior therapy with Bruton tyrosine kinase (BTK) inhibitors unless the subject was intolerant of BTK therapy or subject had disease progression
  • Subjects with CLL/SLL must have prior treatment with BTK inhibitor and must have had progression or recurrence while on treatment of within 12 mos from BTK treatment
  • Subject must have failed at least 1 prior systemic therapy
  • QT-interval corrected according to Fridericia's formula (QTcF) ≤ 450 milliseconds (ms)
Show all 28Show fewer
  • Left ventricular ejection fraction > 50%
  • For subjects, except those with CLL, must have at least one bi-dimensionally measurable nodal lesion >1.5 cm, as defined by Lugano Classification
  • Willingness to participate in collection of pharmacokinetic samples
  • A negative serum pregnancy test within 14 days of study Day 0, for females of childbearing potential
  • Diagnosis of relapsed/refractory CLL SLL or FL, MZL, DLBCL and high-grade B-cell lymphoma. Subjects must meet the following criteria for relapsed or refractory disease:
  • No prior therapy with PI3Kδ inhibitors
  • No prior therapy with Bruton tyrosine kinase (BTK) inhibitors unless the subject was intolerant of BTK therapy or subject had disease progression
  • Subjects with CLL, SLL, FL, and MZL must have a failure of at least 1 prior systemic therapy and be considered by the investigator a candidate for therapy with a rituximab-based regimen; subjects with DLBCL and high-grade B-cell lymphoma must have a failure of at least 2 prior therapies.
  • QT-interval corrected according to Fridericia's formula (QTcF) ≤450 milliseconds (ms)
  • Left ventricular ejection fraction > 50%
  • For subjects, except those with CLL, must have at least one bi-dimensionally measurable nodal lesion >1.5 cm, as defined by Lugano Classification
  • Willingness to participate in collection of pharmacokinetic samples
  • A negative serum pregnancy test within 14 days of study Day 0 for females of childbearing potential
  • Diagnosis of relapsed/refractory CLL or histologically-confirmed relapsed/refractory SLL or FL, MZL, MCL, DLBCL NOS (germinal center B-cell type or activated B-cell type)
  • No prior therapy with PI3Kδ inhibitors
  • No prior therapy with BTK inhibitors
  • Subjects with CLL, SLL, FL, MCL, and MZL must have a failure of at least 1 prior systemic therapy, require treatment in the opinion of the investigator, and be considered by the investigator a candidate for therapy subjects with DLBCL and high-grade B-cell lymphoma must have a failure of at least 2 prior therapies
  • For subjects with SLL, FL, MZL, MCL, DLBCL: At least one bi dimensionally measurable nodal lesion > 1.5 cm in its longest diameter by CT scan or MRI
  • QT-interval corrected according to Fridericia's formula (QTcF) ≤ 450 milliseconds (msec)
  • Left ventricular ejection fraction > 50% as measured by echocardiogram or multigated acquisition (MUGA) scan
  • Willingness to participate in collection of pharmacokinetic samples
  • For females of childbearing potential, a negative serum pregnancy test within 14 days of study Day 0

Who cannot join

  • Known histological transformation from CLL to an aggressive lymphoma
  • Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
  • Subjects who have tested positive for hepatitis B surface antigen and/or hepatitis B core antibody
  • Positive for hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody
  • Ongoing drug-induced pneumonitis
  • History of clinically significant cardiovascular abnormalities
  • History of severe bleeding disorders (ME-401 plus zanubrutinib arm only)
  • Known central nervous system (CNS) hemorrhage or stroke within 6 months prior to start of study drugs (ME-401 plus zanubrutinib arm only)

Trial locations and contacts

24 sites in 2 countries.

24 sites in 2 countries

United States23 sites

  • Memorial Sloan Kettering

    Basking Ridge, New Jersey, 07920

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana Farber

    Boston, Massachusetts, 02215

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Memorial Sloan Kettering

    Commack, New York, 11725

  • Compassionate Care

    Corona, California, 92708

  • University of Southwestern Medical Center

    Dallas, Texas, 75390

  • Swedish Cancer Institute

    Edmonds, Washington, 98026

  • Memorial Sloan Kettering

    Harrison, New York, 10604

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Swedish Cancer Institute

    Issaquah, Washington, 98029

  • Carbone Cancer Center

    Madison, Wisconsin, 53792

  • Sylvester Comprehensive Cancer Center (Univ of Miami School of Med)

    Miami, Florida, 33136

  • Memorial Sloan Kettering

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering

    Montvale, New Jersey, 07645

  • Vanderbilt

    Nashville, Tennessee, 37240

  • NYU Langone Laura & Isaac - Perlmutter Cancer Center

    New York, New York, 10016

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • Swedish Cancer Center

    Seattle, Washington, 98104

  • Stony Brook

    Stony Brook, New York, 11794

  • University of Arizona

    Tucson, Arizona, 85724

  • Memorial Sloan Kettering

    Uniondale, New York, 11553

Other trials in United States

Switzerland1 site

  • lstituto Oncologico della Svizzera ltaliana Ospedale Regionale Bellinzona e Valli CH

    Bellinzona

Other trials in Switzerland

About this study

Official title: A Three-Arm Study of ME-401 Monotherapy in Subjects With Relapsed/Refractory CLL, SLL, or FL, of ME-401 in Combination With Rituximab in Subjects With Relapsed/Refractory CLL/SLL or B-cell NHL, and of ME-401 in Combination With Zanubrutinib in Subjects With Relapsed/Refractory CLL/SLL or B-cell NHL

A Three-Arm Study of ME-401 in Subjects with Relapsed/Refractory CLL/SLL or FL, of ME-401 in Combination with Rituximab in Subjects with Relapsed/Refractory CLL/SLL or B-cell NHL, and of ME-401 in Combination with Zanubrutinib in Subjects with Relapsed/Refractory CLL/SLL or B-cell NHL

Read the detailed description

This is a three-arm study of ME-401 alone, of ME-401 in combination with rituximab, and of ME-401 in combination with zanubrutinib in subjects with relapsed/refractory CLL/SLL or B cell NHL. The 3 arms of the study will be conducted in parallel, with subject allocation to ME-401 alone, ME-401 plus rituximab, or ME-401 plus zanubrutinib based on disease type and availability of an open enrollment slot.

Being tested
ME-401, Rituximab, Zanubrutinib
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell

What participants receive

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

  • ME-401Drug

    60 mg

  • RituximabDrug

    Also called Rituxan

    IV infusion 375 mg/m2

  • ZanubrutinibDrug

    80 and 160 mg bid

Study groups in NCT02914938
Study groupRoleWhat they receive
ME-401 AloneExperimentalThis arm is an open-label, dose escalation study to determine the safety, efficacy and pharmacokinetics of ME-401 along with the mBED, MTD, and DLTs. There are 4 planned cohorts which may enroll up to 61 subjects.
Receives: Drug: ME-401
ME-401 in Combination with RituximabExperimentalThe second arm is an open label study to evaluate the safety, efficacy, and pharmacokinetics of ME-401 in combination with rituximab in subjects with various B-cell malignancies. There are two planned cohorts which may enroll up to 30 subjects.
Receives: Drug: ME-401; Drug: Rituximab
ME-401 in Combination with ZanubrutinibExperimentalThe third arm is an open label study evaluating the safety, efficacy, MTD, DLT and pharmacokinetics of ME-401 in combination with zanubrutinib in subjects with various B-cell malignancies. This arm will include 2 stages: a safety evaluation stage (cohort of 6-12 subjects) and a disease-specific expansion cohort stage (up to 74 subjects).
Receives: Drug: ME-401; Drug: Zanubrutinib

What is being measured

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

  1. Minimum Biologically Effective Dose (mBED) of ME-401 alone

    The mBED will be defined as the dose that is safe and that achieves an objective response rate that is not less than 30%.

    Measured: 1 year

  2. Maximally Tolerated Dose (MTD) of ME-401 alone

    The MTD will be determined as the maximum dose that is safe. DLT rate closest to .25 and not to exceed 2 DLTs in 6 subjects

    Measured: 1 year

  3. Dose Limiting Toxicities (DLTs) of ME-401 alone

    DLTs will be measured by the number of treatment related AEs that occur within the first 56 days of ME-401 administration, is considered clinically significant by the P.I. and occurs in the presence of supportive care

    Measured: within the first 56 days

  4. Evaluate the safety and tolerability of ME-401 plus rituximab

    Safety and tolerability will be measured by the number of treatment related AEs

    Measured: 1 year

  5. Determine the MTD of ME-401 plus zanubrutinib

    The MTD of ME-401 is defined as the dose level with a DLT rate closest to 0.25.

    Measured: 1 year

  6. Determine the DLTs of ME-401 plus zanubrutinib

    DLTs will be measured by the number of treatment related AEs that occur within the first 56 days of ME-401 plus zanubrutinib

    Measured: within the first 56 days

  7. Evaluate the safety and tolerability of ME-401 plus zanubrutinib

    Safety and tolerability will be measured by the number of treatment related AEs

    Measured: 1 year

Secondary outcomes (10)

  1. Safety profile of ME-401 alone

    Safety profile will be measured by number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Measured: 1 year

  2. Efficacy of ME-401 alone as assessed by (OR)

    The efficacy of ME-401 alone will be assessed by the overall response (OR) of subjects which is calculated as the percent of subjects achieving complete response (CR), minimal disease negativity (MRD), duration of response (DOR) and progression free survival (PFS).

    Measured: 2 years

  3. Evaluate the (AUC) PK of ME-401 alone

    Determined by the Area Under the Concentration time curve (AUC)

    Measured: 2 years

  4. Evaluate the PK (Cmax) of ME-401 alone

    Determined by Peak Plasma Concentration (Cmax)

    Measured: 2 years

  5. Efficacy of ME-401 with rituximab

    The efficacy of ME-401 with Rituximab will be determined by the overall response (OR) of subjects calculated as the percent of subjects achieving a complete remission (CR), duration of response (DOR) or Progression Free survival (PFS) according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL)

    Measured: 2 years

  6. Evaluate the PK (AUC) of ME-401 with rituximab

    Determined by the Area Under the Concentration time curve (AUC)

    Measured: 2 years

  7. Evaluate the PK (Cmax) of ME-401 with rituximab

    Determined by Peak Plasma Concentration (Cmax)

    Measured: 2 years

  8. Efficacy of ME-401 with zanubrutinib

    The efficacy of ME-401 with zanubrutinib will be assessed by the overall response (OR) of subjects calculated as the percent of subjects achieving a complete remission (CR), Duration of response (DOR) and progression free survival (PFS)

    Measured: 2 years

  9. Evaluate the PK (AUC) of ME-401 in combination with zanubrutinib

    Determined by the Area Under the Concentration time curve (AUC)

    Measured: 2 years

  10. Evaluate the PK (Cmax) of ME-401 in combination with zanubrutinib

    Determined by Peak Plasma Concentration (Cmax)

    Measured: 2 years

Timeline

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

  1. First posted26 Sep 2016 (estimated)
  2. Study startOct 2016
  3. Primary completion29 Mar 2023
  4. Study completion29 Mar 2023

Why it stopped: discontinuation of zandelisib program

Resources

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
Parallel groups
Model description
This is a three-arm study of ME-401 alone, of ME-401 in combination with rituximab, and of ME-401 in combination with zanubrutinib in subjects with relapsed/refractory CLL/SLL or B cell NHL. The 3 arms of the study will be conducted in parallel, with subject allocation to ME 401 alone, ME-401 plus rituximab, or ME 401 plus zanubrutinib based on disease type and availability of an open enrollment slot.
Masking
None (open label)
Enrolment
97 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02914938
Sponsor's protocol ID
ME-401-002
Status last verified
Dec 2022
First submitted
12 Sep 2016
Last updated
9 May 2023
Results posted
No
Data monitoring committee
No

Publications

  • Pagel JM, Soumerai JD, Reddy N, Jagadeesh D, Stathis A, Asch A, Salman H, Kenkre VP, Iasonos A, Llorin-Sangalang J, Li J, Zelenetz AD. Zandelisib with continuous or intermittent dosing as monotherapy or in combination with rituximab in patients with relapsed or refractory B-cell malignancy: a multicentre, first-in-patient, dose-escalation and dose-expansion, phase 1b trial. Lancet Oncol. 2022 Aug;23(8):1021-1030. doi: 10.1016/S1470-2045(22)00333-3. Epub 2022 Jul 11.

    PubMed 35835137

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ME-401, Rituximab and Zanubrutinib in people with Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL), run by MEI Pharma, Inc. at 24 sites in 2 countries.

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 28 inclusion and 8 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: stopped early, as of the sponsor's last update on 9 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Switzerland. 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?

The study was stopped early (reason given: discontinuation of zandelisib program). Results are not available in the source record.

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?

Minimum Biologically Effective Dose (mBED) of ME-401 alone (time frame: 1 year). The study lists 7 primary outcomes in all. 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 NCT02914938, which also lists 1 linked publication.

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 9 May 2023.

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