Clinical Trials /

Pembrolizumab in Treating Patients With Stage IB-IV Mycosis Fungoides

NCT03695471

Description:

This phase II trial studies how well pembrolizumab works in treating patients with stage IB-IV mycosis fungoides. Antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread.

Related Conditions:
  • Mycosis Fungoides
  • Sezary Syndrome
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Treating Patients With Stage IB-IV Mycosis Fungoides
  • Official Title: A Phase II, Open-Label, Single-Arm Trial Using KEYTRUDA (Pembrolizumab) as Initial Systemic Therapy in the Treatment of Advanced Mycosis Fungoides

Clinical Trial IDs

  • ORG STUDY ID: MC1788
  • SECONDARY ID: NCI-2018-02023
  • SECONDARY ID: MC1788
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT03695471

Conditions

  • Mycosis Fungoides
  • Sezary Syndrome
  • Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage II Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IIA Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage III Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IIIA Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IIIB Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IV Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IVA1 Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IVA2 Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IVB Mycosis Fungoides and Sezary Syndrome AJCC v8

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab)

Purpose

This phase II trial studies how well pembrolizumab works in treating patients with stage IB-IV mycosis fungoides. Antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the antitumor activity of pembrolizumab in patients with advanced mycosis
      fungoides (MF) as initial systemic therapy.

      SECONDARY OBJECTIVES:

      I. To evaluate safety of pembrolizumab in this patient population. II. To evaluate response
      rates of pembrolizumab in this patient population. III. To determine the progression free
      survival, duration of response, time to response and overall survival of pembrolizumab in
      this patient population.

      CORRELATIVE OBJECTIVES:

      I. To characterize the histologic features of the anti-tumor response in patients with
      advanced MF before and after treatment with pembrolizumab.

      OUTLINE:

      Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats
      every 21 days for up to 9 courses in the absence of disease progression or unacceptable
      toxicity. Patients receiving complete response during courses 2-9 are held for the remaining
      courses. If patients relapse while treatment is being held, the patient will then complete
      remaining courses.

      After completion of study treatment, patients are followed up at 30 and 90 days, and then
      every 3 months for up to 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 9 courses in the absence of disease progression or unacceptable toxicity. Patients receiving complete response during courses 2-9 are held for the remaining courses. If patients relapse while treatment is being held, the patient will then complete remaining courses.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histological confirmation of one of the following:

               -  Stage IIB-IV mycosis fungoides not previously treated with systemic therapy

               -  Stage IB/IIA mycosis fungoides with Modified Severity Weighted Assessment Tool
                  (mSWAT) >= 20 with high risk morphologic features defined as thick plaque disease
                  and/or follicular involvement who have failed one form of skin-directed therapy.

               -  Sezary syndrome patients not previously treated with systemic therapy.

          -  Measurable disease based on mSWAT and/or Response Evaluation Criteria in Solid Tumors
             (RECIST) 1.1.

          -  Be willing to provide tissue from a newly obtained core or excisional biopsy of a
             tumor lesion. Note: Newly-obtained is defined as a specimen obtained up to 6 weeks (42
             days) prior to registration. Exception: Subjects for whom newly-obtained samples
             cannot be provided (e.g. inaccessible or subject safety concern) may submit an
             archived specimen only upon agreement from the Sponsor.

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.

          -  Absolute neutrophil count (ANC) >= 1,500 /mcL (obtained =< 28 days prior to
             registration)

          -  Platelet count >= 100,000/mcL (obtained =< 28 days prior to registration)

          -  Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO)
             dependency (within 7 days of assessment) (obtained =< 28 days prior to registration)

          -  Serum total bilirubin =< 1.5 X upper limit of normal (ULN) OR direct bilirubin =< ULN
             for subjects with total bilirubin levels > 1.5 ULN (obtained =< 28 days prior to
             registration)

          -  Aspartate transaminase (AST) and alanine transaminase (ALT) =< 2.5 X ULN OR =< 5 X ULN
             for subjects with liver metastases (obtained =< 28 days prior to registration)

          -  Albumin > 2.5 mg/dL (obtained =< 28 days prior to registration)

          -  Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated
             creatinine clearance >= 60 ml/min for subject with creatinine levels > 1.5 x
             institutional ULN (obtained =< 28 days prior to registration)

          -  Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin
             time (PTT) =< 1.5 X ULN OR if patient is receiving anticoagulant therapy and PT/INR or
             PTT is within therapeutic range of intended use of coagulants (obtained =< 28 days
             prior to registration)

          -  Negative urine or serum pregnancy test done =< 28 days prior to registration and =< 72
             hours prior to receiving the first dose of study medication, for women of childbearing
             potential only.

          -  Female subjects of childbearing potential must be willing to use an adequate method of
             contraception for the course of the study through 120 days after the last dose of the
             study medication.

               -  Note: Abstinence is acceptable if this is the usual lifestyle and preferred
                  contraception for the subject.

          -  Male subjects of childbearing potential must agree to use an adequate method of
             contraception for the course of the study through 120 days after the last dose of the
             study medication.

               -  Note: Abstinence is acceptable if this is the usual lifestyle and preferred
                  contraception for the subject.

          -  Provide written informed consent.

          -  Willing to return to enrolling institution for follow-up (during the Active Monitoring
             Phase of the study).

          -  Willing to provide tissue samples for correlative research purposes.

        Exclusion Criteria:

          -  Any of the following because this study involves: an agent that has known genotoxic,
             mutagenic and teratogenic effects:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Is currently participating and receiving study therapy or have participated in a study
             of an investigational agent and received study therapy or used an investigational
             device =< 4 weeks prior to registration.

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy =< 7 days prior to registration.

          -  Has a known history of active TB (Bacillus tuberculosis).

          -  Hypersensitivity to pembrolizumab or any of its excipients.

          -  Has had a prior anti-cancer monoclonal antibody (mAb) =< 4 weeks prior to registration
             or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to
             agents administered more than 4 weeks earlier.

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy =< 2
             weeks prior to registration or who has not recovered (i.e., =< grade 1 or at baseline)
             from adverse events due to a previously administered agent.

               -  Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and
                  may qualify for the study.

               -  Note: If subject received major surgery, they must have recovered adequately from
                  the toxicity and/or complications from the intervention prior to starting
                  therapy.

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions: basal cell carcinoma of the skin or squamous cell carcinoma of the skin
             that has undergone potentially curative therapy or in situ cervical cancer.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Exceptions: subjects with previously treated brain metastases may
             participate provided they are stable (without evidence of progression by imaging =< 4
             weeks prior to registration 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 registration. This exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability.

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Note: Replacement therapy (eg., thyroxine, insulin, or physiologic
             corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
             not considered a form of systemic treatment.

          -  Has a history of non-infectious pneumonitis that required steroids or has current
             pneumonitis.

          -  Has an active infection requiring systemic therapy.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject?s
             participation for the full duration of the trial, or is not in the best interest of
             the subject 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.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the screening visit through 120 days
             after the last dose of trial treatment.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).

          -  Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
             Hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
             detected).

          -  Has received a live vaccine =< 30 days prior to registration.

               -  Note: Seasonal influenza vaccines for injection are generally inactivated flu
                  vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist)
                  are live attenuated vaccines, and are not allowed.

          -  Sezary syndrome patients with high blood burden requiring immediate cytoreduction.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall cutaneous response (cutaneous complete response [CR], cutaneous 90 response [CR90] or cutaneous partial response [PR])
Time Frame:Up to 1 year
Safety Issue:
Description:Will be assessed by the Modified Severity Weighted Assessment Tool (mSWAT). All calculated values will use the last-observation-carried forward for any participants who withdraw, are lost to follow up, or exit the study per protocol. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients will be analyzed using Mann?Whitney U for nonparametric data and the student t-test. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 90 days after last dose
Safety Issue:
Description:The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
Measure:Changes in mSWAT scores
Time Frame:Baseline and course 9
Safety Issue:
Description:Summary statistics will be calculated. Proportions of patients will be calculated and described using summary statistics. Proportions of interest are patients having CR, CR90 and PR; patients having stable subcutaneous disease; patients having progressive cutaneous disease; and patients having an overall systemic response rate. mSWAT is calculated using body surface area (BSA) of each MF lesion (palm plus fingers of the patient ≈ 1% BSA) in each of 12 areas of the body, multiplying the sum of the BSA of each lesion type by a weighting factor (patch=1, plaque=2, and tumor =3) and generating a sum of the subtotals of each lesion subtype.
Measure:Progression free survival
Time Frame:Time from registration to relapse or death due to any cause, assessed up to 5 years
Safety Issue:
Description:The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. In addition, the progression-free survival rate at 5 years after registration will be reported.
Measure:Duration of response
Time Frame:Up to 1 year
Safety Issue:
Description:The distribution of duration of complete response will be estimated using the method of Kaplan-Meier.
Measure:Time to response
Time Frame:Time from registration to CR, CR90 or PR, assessed up to 1 year
Safety Issue:
Description:The distribution of survival time will be estimated using the method of Kaplan-Meier.
Measure:Overall survival
Time Frame:Time from registration to death due to any cause, assessed up to 2 years
Safety Issue:
Description:The distribution of survival time will be estimated using the method of Kaplan-Meier. In addition, the overall survival rate at 2 years after registration will be reported.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

Last Updated

January 29, 2020