Pembrolizumab in Treating Patients With Relapsed or Refractory Stage IB-IVB Mycosis Fungoides or Sezary Syndrome

NCT02243579 | Completed Phase 2 Results

• 4 other identifiers: NCI-2014-00709CITN-10P30CA015704U01CA154967
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 8

Brief Summary

This phase II trial studies how well pembrolizumab works in treating patients with stage IB-IVB mycosis fungoides or Sezary syndrome that has returned after a period of improvement or has not responded to at least one type of treatment. Monoclonal antibodies, such as pembrolizumab, may block cancer growth in different ways by targeting certain cells.

Conditions

Recurrent Mycosis Fungoides and Sezary Syndrome; Refractory Mycosis Fungoides and Sezary Syndrome; Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIIA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIIB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IVA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IVB Mycosis Fungoides and Sezary Syndrome AJCC v7

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR), Defined as a Confirmed Partial Response (PR) or Complete Response (CR) Using Global Assessment Standard Response Criteria for Mycosis Fungoides and Sezary Syndrome

  A generalized linear model for the objective response rate used a binominal error distribution. The model included as covariates all available baseline predictors of the missing outcomes.

  Up to 3.2 years

Secondary Outcomes (5)

• Duration of Response

  The time interval between the date of first response (CR/PR) and the date of progression as assessed by standard Mycosis Fungoides and Sezary Syndrome response criteria, assessed at 26 and 52 weeks

• Progression Free Survival (PFS)

  The time from allocation to the first documented disease progression or death due to any cause, whichever occurs first, assessed at 26 and 52 weeks

• Overall Survival (OS)

  The time from randomization to death due to any cause, assessed at 52, 104 and 156 weeks

• Time to Onset of First Drug-related Toxicity

  Up to 4 years

• Incidence of Adverse Events Graded Using the Common Terminology Criteria for Adverse Events Version 5.0

  Up to 4 years

Study Arms (1)

Treatment (pembrolizumab)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• This trial will include subjects with stage IB-IVB MF/SS (maximal stage since diagnosis will determine eligibility), and who have relapsed, are refractory, or progressed after at least one standard systemic therapy; current disease stage at time of entry will also be documented but will not be used for eligibility
• Subjects must have the following minimum wash-out and adverse event (AE) recovery period from previous treatments without treatment between documentation of relapse/progression and enrollment of specifically:
• \>= 2 weeks for local radiation therapy
• \>= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational agents that are not defined as immunotherapy, or for tumor-targeting monoclonal antibodies (mAbs) with the exception of alemtuzumab for which the washout is at least 8 weeks
• \>= 15 weeks for anti-cluster of differentiation (CD)137 or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• \>= 2 weeks from resolution (i.e., =\< grade 1 or at baseline) from AEs due to procedures performed or therapeutic agents administered
• \>= 2 weeks for retinoids, interferons, vorinostat, romidepsin, denileukin diftitox, and therapeutic doses of oral corticosteroids (physiologic replacement doses of oral corticosteroids are allowed, topical corticosteroids are allowed)
• \>= 2 weeks for phototherapy
• \>= 1 week for topical therapy (including retinoid, nitrogen mustard, or imiquimod)
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Life expectancy of at least 6 months
• Performed within 10 days of treatment initiation: Leukocytes \>= 2,000/mcL
• Performed within 10 days of treatment initiation: Absolute neutrophil count \>= 1,500/mcL
• Performed within 10 days of treatment initiation: Platelets \>= 100,000/mcL
• Performed within 10 days of treatment initiation: Hemoglobin \>= 9 g/dL OR \>= 5.6 mmol/L

You may not qualify if:

• Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Note: patients with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Patients who are currently participating in or have participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving therapeutic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from AEs due to agents administered more than 4 weeks earlier
• 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, or in situ cervical cancer that has undergone potentially curative therapy
• Patients with known brain metastases should be excluded from this clinical trial
• Patients with carcinomatous meningitis should also be excluded
• Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; the use of physiologic doses of corticosteroids may be approved after consultation with the protocol principal investigator (PI) and Cancer Immunotherapy Trials Network (CITN); patients with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study
• 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 known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand (L)1, anti-PD-L2

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (8)

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Related Publications (2)

• Phillips D, Matusiak M, Gutierrez BR, Bhate SS, Barlow GL, Jiang S, Demeter J, Smythe KS, Pierce RH, Fling SP, Ramchurren N, Cheever MA, Goltsev Y, West RB, Khodadoust MS, Kim YH, Schurch CM, Nolan GP. Immune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphoma. Nat Commun. 2021 Nov 18;12(1):6726. doi: 10.1038/s41467-021-26974-6.

  PMID: 34795254 DERIVED

• Khodadoust MS, Rook AH, Porcu P, Foss F, Moskowitz AJ, Shustov A, Shanbhag S, Sokol L, Fling SP, Ramchurren N, Pierce R, Davis A, Shine R, Li S, Fong S, Kim J, Yang Y, Blumenschein WM, Yearley JH, Das B, Patidar R, Datta V, Cantu E, McCutcheon JN, Karlovich C, Williams PM, Subrahmanyam PB, Maecker HT, Horwitz SM, Sharon E, Kohrt HE, Cheever MA, Kim YH. Pembrolizumab in Relapsed and Refractory Mycosis Fungoides and Sezary Syndrome: A Multicenter Phase II Study. J Clin Oncol. 2020 Jan 1;38(1):20-28. doi: 10.1200/JCO.19.01056. Epub 2019 Sep 18.

  PMID: 31532724 DERIVED

MeSH Terms

Conditions

Mycosis Fungoides; Sezary Syndrome

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Asa Davis
• Organization: Fred Hutchinson Cancer Research Center

akdavis@fredhutch.org

206-667-5300

Study Officials

• Youn Kim

  Cancer Immunotherapy Trials Network

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2014
• First Posted: September 18, 2014
• Study Start: October 15, 2014
• Primary Completion: January 4, 2018
• Study Completion: April 1, 2019
• Last Updated: September 20, 2019
• Results First Posted: February 5, 2019

Record last verified: 2019-08

Locations

US (8)