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

NCT03309878 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: NCI-2017-0186519-01810106UM1CA186691
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 8

Brief 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). 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.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma; Recurrent High Grade B-Cell Lymphoma; Recurrent Transformed B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory High Grade B-Cell Lymphoma; Refractory Transformed B-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to 6 weeks

• 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).

  Up to 25 months

• Progression-free Survival (PFS) (Phase II)

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

  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)

• Overall Response Rate

  Up to 25 months

• Complete Response Rate

  Up to 25 months

• Partial Response Rate

  Up to 25 months

• Duration of Response

  Up to 25 months

Other Outcomes (1)

• Biomarker Analysis

  Up to 25 months

Study Arms (2)

Arm I (pembrolizumab, mogamulizumab)

EXPERIMENTAL

Patients 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.

Biological: Mogamulizumab; Biological: Pembrolizumab

Arm II (pembrolizumab)

EXPERIMENTAL

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.

Biological: Pembrolizumab

Interventions

Mogamulizumab BIOLOGICAL

Given IV

Also known as: 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, Poteligeo

Arm I (pembrolizumab, mogamulizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, Keytruda, Lambrolizumab, MK-3475, Pembrolizumab Biosimilar BCD-201, SCH 900475

Arm I (pembrolizumab, mogamulizumab); Arm II (pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (8)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Publications (1)

• 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.

  PMID: 41595202 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

mogamulizumab; Immunoglobulin G; Disulfides; pembrolizumab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Results Point of Contact

• Title: Grants Administrative Manager
• Organization: Johns Hopkins University

JHCCCRO@jhmi.edu

443-927-3568

Study Officials

• Erel Joffe

  JHU Sidney Kimmel Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2017
• First Posted: October 16, 2017
• Study Start: October 24, 2018
• Primary Completion: January 6, 2021
• Study Completion: April 11, 2023
• Last Updated: September 21, 2023
• Results First Posted: June 7, 2023

Record last verified: 2023-08

Locations

US (8)