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Recurrent Diffuse Large B-Cell LymphomaPhase 1/2NCT03309878

Mogamulizumab and Pembrolizumab in Treating Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma

A Phase 1/2 study testing Mogamulizumab and Pembrolizumab in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent High Grade B-Cell Lymphoma, run by National Cancer Institute (NCI) at 8 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 phase I/II trial studies the best dose and side effects of mogamulizumab in combination with pembrolizumab and to see how well they work in treating patients with diffuse large B cell lymphoma that have come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Mogamulizumab and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
8 sitesUnited States
Study dates
24 Oct 2018to 11 Apr 2023
Phase
Phase 1/2
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

  • Patients must have histologically confirmed diffuse large B-cell lymphoma; all subtypes of diffuse large B-cell lymphoma are eligible, including high-grade B-cell lymphoma and diffuse large B-cell lymphoma (DLBCL) that has transformed from a prior indolent B-cell non-Hodgkin lymphoma
  • Patients must have measurable disease per 2014 Lugano Classification Criteria which is defined as at least one nodal lesion measuring > 1.5 cm in greatest diameter or at least one extranodal lesion measuring > 1.0 cm in greatest diameter
  • For phase 2: patients and received at least 2 prior lines of therapy and must have previously received, refused, or been deemed ineligible for autologous stem cell transplantation
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 80%)
  • Absolute neutrophil count >= 1,500/mcL (if neutropenia is related to bone marrow involvement with lymphoma, the absolute neutrophil count must be >= 1,000/mcL)
  • Platelets >= 75,000/mcL (if thrombocytopenia is related to bone marrow involvement with lymphoma, the platelet count must be >= 50,000/mcL)
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  • Hemoglobin >= 9 g/dL (if anemia is related to bone marrow involvement with lymphoma, the hemoglobin must be >= 8 g/dL)
  • Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN) or < 3 x the ULN for indirect bilirubin in patients with Gilbert's disease
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal
  • Creatinine =< 1.5 x institutional upper limit of normal OR measured or calculated creatinine clearance if creatinine > 1.5 x ULN then creatinine clearance >= 40 mL/min/1.73 m^2 as calculated by Cockcroft and Gault equation
  • Life expectancy of greater than 3 months
  • The effects of MK-3475 (pembrolizumab) in combination with KW-0761 (mogamulizumab) on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and 6 months after completion of MK-3475 (pembrolizumab) in combination with KW-0761 (mogamulizumab) administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of MK-3475 (pembrolizumab) in combination with KW-0761 (mogamulizumab) administration
  • Submit adequate archival tissue specimen (25+ unstained slides or 2 tissue blocks) from a biopsy performed after progression of disease on most recent therapy OR subject is willing to undergo a new core or excisional biopsy to obtain evaluable tumor tissue sample for immunohistochemical assessment and sequencing for B2M loss; repeat samples may be required if adequate tissue is not provided, however, patients may still be considered for enrollment on a case by case basis following consultation with the principal investigator (PI)
  • Ability to understand and the willingness to sign a written informed consent document
  • Subjects with prior history of chemotherapy-induced or radiation-induced pulmonary toxicity require confirmation of diffuse capacity of the lung for carbon monoxide (DLCO) over 60% (adjusted for hemoglobin) by a pulmonary function test prior to study enrollment

Who cannot join

  • Patients who have had previous systemic anti-cancer therapy within 3 weeks of registration or those who have not recovered from adverse events due to agents administered previously
  • Note: Patients are considered enrolled on the study after protocol registration and not after signing consent
  • Patients who are receiving any other concurrent investigational agents
  • Patient is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment; the use of physiologic doses of corticosteroids (e.g. prednisone =< 20 mg/d) may be approved after consultation with the study PI; topical or inhaled corticosteroids are allowed
  • Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer
  • Patients with active cerebral or meningeal involvement by lymphoma should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound evaluation of neurologic and other adverse events
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  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475 (pembrolizumab) or KW-0761 (mogamulizumab)
  • Subject with active autoimmune disease; subjects with vitiligo, eczema, alopecia, type I diabetes mellitus, psoriasis not requiring systemic treatment, or endocrine deficiencies (such as hypothyroidism) managed with replacement hormones, including physiologic corticosteroid replacement therapy are eligible
  • Has a history or currently active (non-infectious) pneumonitis that required steroids unless prior history of chemotherapy or radiotherapy induced pneumonitis meeting the eligibility criteria
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  • Prior allogeneic stem cell transplant (SCT)
  • Patients who are planning to receive allogeneic SCT in the near future as preliminary reports suggest added toxicity in patients undergoing allogeneic stem cell transplantation after having received mogamulizumab
  • Autologous SCT =< 90 days prior to first dose of study drug
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because MK-3475 (pembrolizumab) is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MK-3475 (pembrolizumab), breastfeeding should be discontinued if the mother is treated with MK-3475 (pembrolizumab); these potential risks may also apply to KW-0761 (mogamulizumab)
  • MK-3475 (pembrolizumab) and KW-0761 (mogamulizumab) may have adverse effects on a fetus in utero; furthermore, it is not known if MK-3475 (pembrolizumab) or KW-0761 (mogamulizumab) has transient adverse effects on the composition of sperm; patients are excluded from this study if pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of trial treatment
  • Patients with human immunodeficiency virus (HIV) are excluded if they have a detectable viral load, are not on a stable antiretroviral regimen, have a decreased CD4+ T-cell count (< 500), or require prophylactic antibiotics for the prevention of opportunistic infections
  • Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection
  • Note: No testing for hepatitis B and hepatitis C is required unless mandated by local health authority
  • Has a known history of active tuberculosis (TB)
  • Patients with significant cardiac disease (e.g., New York Heart Association [NYHA] class III-IV congestive heart failure, unstable angina, recent myocardial infarction within the last 6 months, etc.)

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

Other trials in United States

About this study

Official title: A Phase I and Randomized Phase II Study of KW-0761 (Mogamulizumab) and MK-3475 (Pembrolizumab) in Relapsed, Refractory Diffuse Large-B Cell Lymphoma

This phase I/II trial studies the best dose and side effects of mogamulizumab in combination with pembrolizumab and to see how well they work in treating patients with diffuse large B cell lymphoma that have come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as mogamulizumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of KW-0761 (mogamulizumab) when administered in combination with MK-3475 (pembrolizumab) in patients with relapsed, refractory diffuse large B-cell lymphoma. (Phase I) II. To assess the safety and tolerability of KW-0761 (mogamulizumab) when administered in combination with MK-3475 (pembrolizumab) in patients with relapsed, refractory diffuse large B-cell lymphoma. (Phase I) III. To assess the progression-free survival of KW-0761 (mogamulizumab) when administered in combination with MK-3475 (pembrolizumab) compared to MK-3475 (pembrolizumab) alone in patients with relapsed and refractory diffuse large B-cell lymphomas. (Phase II)

SECONDARY OBJECTIVES:

  1. To observe and record anti-tumor activity. (Phase I) II. To assess the overall response rate, complete response rate, partial response rate, duration of response of KW-0761 (mogamulizumab) and MK-3475 (pembrolizumab) compared to MK-3475 (pembrolizumab) alone in patients with relapsed and refractory diffuse large B-cell lymphomas. (Phase II)

EXPLORATORY OBJECTIVES:

  1. To determine whether the progression-free survival of KW-0761 (mogamulizumab) and MK-3475 (pembrolizumab) when administered to patients with relapsed and refractory diffuse large B-cell lymphomas differs based on the presence or absence of mutations in B2M or CD58 or amplifications in PD-L1.

II. To determine whether the progression-free survival of KW-0761 (mogamulizumab) and MK-3475 (pembrolizumab) when administered to patients with relapsed and refractory diffuse large B-cell lymphomas differs based on changes in CD8 T-cell, natural killer (NK) cell, and FoxP3+ regulatory T cell (Treg) prevalence in response to therapy as measured by immunohistochemistry.

III. To determine whether KW-0761 (mogamulizumab) and MK-3475 (pembrolizumab) alters the prevalence of peripheral blood CCR4+/FoxP3+ regulatory T-cells as well as effector CD4 and CD8 T-cells by multi-parametric flow cytometry.

OUTLINE: This is a phase I, dose-escalation study of mogamulizumab followed by a phase II study. Patients are randomized to 1 of 2 arms.

ARM I: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and mogamulizumab IV over 60 minutes on days 1, 8, and 15 of cycle 1, then day 1 of subsequent courses. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

Being tested
Mogamulizumab, Pembrolizumab
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

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

  • MogamulizumabBiological

    Also called Immunoglobulin G1, Anti-(CC Chemokine Receptor CCR4) (Human-Mouse Monoclonal KW-0761 Heavy Chain), Disulfide With Human-Mouse Monoclonal KW-0761 Kappa-Chain, Dimer, KM8761, KW-0761, Mogamulizumab-kpkc

    Given IV

  • PembrolizumabBiological

    Also called BCD-201, Keytruda, Lambrolizumab, MK-3475

    Given IV

Study groups in NCT03309878
Study groupRoleWhat they receive
Arm I (pembrolizumab, mogamulizumab)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1 and mogamulizumab IV over 60 minutes on days 1, 8, and 15 of cycle 1, then day 1 of subsequent courses. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Mogamulizumab; Biological: Pembrolizumab
Arm II (pembrolizumab)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Pembrolizumab

What is being measured

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

  1. Maximum Tolerated Dose (MTD) or Recommended Phase II Dose (RP2D) of Mogamulizumab in Combination With Pembrolizumab (Phase I)

    Will be determined by dose limiting toxicity (DLT). A standard 3+3 design will be used to find the MTD or RP2D for the combination of pembrolizumab and mogamulizumab.

    Measured: Up to 6 weeks

  2. Incidence of Adverse Events (Phase I)

    Number of incidences of grade 3-5 adverse events at least possibly related to the study intervention will be reported. Adverse events will be graded according to Common Terminology Criteria for Adverse Events version 4.03 (Version 5.0 beginning April 1, 2018).

    Measured: Up to 25 months

  3. Progression-free Survival (PFS) (Phase II)

    The Kaplan Meier method will be used to estimate the median PFS.

    Measured: From course 1 day 1 to the first date of recurrence, progression, or death due to any cause, whichever comes first, assessed up to 12 months

Secondary outcomes (4)

  1. Overall Response Rate

    Will be calculated along with exact 95% confidence intervals.

    Measured: Up to 25 months

  2. Complete Response Rate

    Will be calculated along with exact 95% confidence intervals.

    Measured: Up to 25 months

  3. Partial Response Rate

    Will be calculated along with exact 95% confidence intervals.

    Measured: Up to 25 months

  4. Duration of Response

    Will be summarized by Kaplan-Meier method in patients who achieve complete response (CR) or partial response (PR).

    Measured: Up to 25 months

Timeline

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

  1. First posted16 Oct 2017
  2. Study start24 Oct 2018
  3. Primary completion6 Jan 2021
  4. Study completion11 Apr 2023

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03309878
Sponsor's protocol ID
NCI-2017-01865
Other IDs
NCI-2017-01865, 19-018, 10106, 10106, UM1CA186691
Status last verified
Aug 2023
First submitted
13 Oct 2017
Last updated
21 Sep 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Joffe E, Kumar A, Tuscano JM, Moskowitz AJ, Owens C, Noy A, Palomba ML, Zelenetz AD, Ni A, Sharon E, Vardhana S. Phase I Study of Mogamulizumab in Combination with Pembrolizumab in Patients with Relapsed or Refractory Non-Hodgkin Lymphoma-A National Cancer Institute Experimental Therapeutics Clinical Trials Network (NCI-ETCTN) Trial. Cancers (Basel). 2026 Jan 16;18(2):284. doi: 10.3390/cancers18020284.

    PubMed 41595202

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Mogamulizumab and Pembrolizumab in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent High Grade B-Cell Lymphoma, run by National Cancer Institute (NCI) at 8 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 15 inclusion and 22 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 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 7 Jun 2023). 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?

Maximum Tolerated Dose (MTD) or Recommended Phase II Dose (RP2D) of Mogamulizumab in Combination With Pembrolizumab (Phase I) (time frame: Up to 6 weeks). The study lists 3 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 NCT03309878, 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 21 Sep 2023.

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