Lenalidomide and Cosibelimab for the Treatment of Relapsed/Refractory Mycosis Fungoides or Sézary Syndrome

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorized representative.

  • Assent, when appropriate, will be obtained per institutional guidelines

• Agreement to allow the use of archival tissue from diagnostic tumor biopsies

  • If unavailable, exceptions may be granted with study principal investigator (PI) approval

• Age: ≥ 18 years

• Eastern Cooperative Oncology Group (ECOG) 0-2

• Ability to read and understand English for questionnaires

• Female patients of childbearing potential must have a negative pregnancy test within 24 hours of dosing

• Histologically confirmed mycosis fungoides (MF)/ Sezary syndrome (SS) including transformed MF, stage IB or higher

  • Stage of disease according to tumor, node, metastasis, blood (TNMB) classification.
  • Pathology report must be diagnostic or be consistent with MF/SS criteria
  • SS is defined as meeting T4 plus B2 criteria; where the biopsy of erythrodermic skin may only reveal suggestive but not diagnostic histopathologic features, the diagnosis may be based on either node biopsy or fulfillment of B2 criteria.
  • For MF where the histological diagnosis by light microscopic examination is not confirmed, diagnostic criteria that been recommended by the International Society for Cutaneous Lymphomas (ISCL) should be used

• Have received 1 prior line of systemic therapy (if non-transformed MF)

• Relapsed/ refractory disease

• Measurable disease per Modified Severity Weighted Assessment Tool (mSWAT) and/ or circulating Sezary cell count (Olsen et al. criteria), nodal disease per Lugano

• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy

• Platelets ≥ 75,000/µL. If patient is on full-dose anticoagulation, platelets ≥ 100,000/µL are required

• Hemoglobin ≥ 9g/dL

  • NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment unless cytopenia is secondary to disease involvement

• Total bilirubin < 2.2 × upper limit of normal (ULN)

• Aspartate aminotransferase (AST) ≤ 2.5 x ULN

• Alanine aminotransferase (ALT) ≤ 2.5 x ULN

• Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m^2 (as calculated using the Cockcroft-Gault formula) Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m^2 (as calculated using the Cockcroft-Gault formula)

• If not receiving anticoagulants: activated partial thromboplastin time (aPTT) ≤ 1.3 x ULN. If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants

• International normalized ratio (INR) < 2.5

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test within 24 hours of dosing. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• Agreement by females of childbearing potential to use an effective method of birth control (i.e., failure rate of < 1% per year described below) or abstain from heterosexual activity, and agree to refrain from donating eggs for the course of the study treatment period through at least 30 days after the last dose of lenalidomide, or 4 months after the last dose of cosibelimab whichever is longer

  • A female participant is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a female participant with tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or regulations).

  • Highly effective methods include:

    • Bilateral tubal ligation
    • Partner's vasectomy (if medically confirmed there are no live sperm and sole sexual partner)
    • Hormonal (stopping ovulation with two drugs [estrogen and progesterone]: oral, within the vagina, or on/under the skin; stopping ovulation with one drug progesterone-only: oral, injected, or on/under the skin).
    • Intrauterine hormone-releasing system (IUS)
    • Intrauterine device (IUD)

  • Hormonal contraceptive methods must be supplemented by a barrier method

    • Barrier methods:

      • Male latex or synthetic condom
      • Diaphragm
      • Cervical Cap

• Agreement by males to either practice complete abstinence or agree to use a latex or synthetic condom, even with a successful vasectomy (medically confirmed azoospermia), during sexual contact with a female of childbearing potential, and to agree to refrain from donating sperm for the course of the study treatment period through at least 90 days after the last dose lenalidomide, or 4 months after the last dose of tocilizumab (if applicable) whichever is longer

  • All study participants must be registered into the mandatory revlimid Risk Evaluation and Mitigation Strategies (REMS®) program and be willing and able to comply with the requirements of the REMS® program (including use of aspirin [ASA]/Food and Drug Administration [FDA] approved blood thinner).
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the revlimid REMS® program

Exclusion Criteria:

• Prior therapy with immune checkpoint inhibitors, cell-based therapies, or cancer vaccines

• Thalidomide, lenalidomide, or immunomodulatory imide drug (IMiDS) exposure

• Any skin-directed therapy within 14 days prior to initiating protocol therapy

• Any radiation therapy within 21 days prior to initiating protocol therapy

• Prior stem cell transplantation

• Unstable cardiac disease, as defined by one of the following:

  • Cardiac events such as myocardial infarction (MI) within the past 6 months
  • NYHA (New York Heart Association) heart failure class III-IV
  • Uncontrolled atrial fibrillation or hypertension

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents

• Clinically significant uncontrolled illness

• Active infection requiring antibiotics

• Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• Females only: Pregnant or breastfeeding

• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)