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Extracorporeal Photopheresis and Mogamulizumab for the Treatment of Erythrodermic Cutaneous T Cell Lymphoma

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ClinicalTrials.gov Identifier: NCT04930653
Recruitment Status : Not yet recruiting
First Posted : June 18, 2021
Last Update Posted : August 12, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Brief Summary:
This phase II trial studies the effect of extracorporeal photopheresis (ECP) and mogamulizumab in treating patients with erythrodermic cutaneous T cell lymphoma (CTCL), a type of skin lymphoma. CTCL is a rare type of cancer that begins in the white blood cells called T cells. Erythrodermic is a widespread red rash that may cover most of the body. ECP is a medical treatment that removes blood with a machine, isolates white blood cells and exposes them to ultra violet light, then returns the cells to the body. Mogamulizumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving mogamulizumab with ECP may work together to kill the tumor cells directly (with mogamulizumab) and boost immune response to cancer (with ECP).

Condition or disease Intervention/treatment Phase
Folliculotropic Mycosis Fungoides Primary Cutaneous T-Cell Non-Hodgkin Lymphoma 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 Transformed Mycosis Fungoides Procedure: Extracorporeal Photopheresis Biological: Mogamulizumab Other: Quality-of-Life Assessment Other: Questionnaire Administration Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

I. To assess tolerability and overall response rate (ORR) of the (ECP)/mogamulizumab regimen in CTCL patients previously untreated with mogamulizumab.

SECONDARY OBJECTIVES:

I. To estimate complete response (CR) rate, time to response, duration of response, progression free survival, and overall survival in CTCL patients treated with the ECP/mogamulizumab combination.

II. To summarize the toxicities in CTCL patients treated with the ECP/mogamulizumab combination.

EXPLORATORY OBJECTIVES:

I. To assess quality of life (QoL) parameters before, during, and after the regimen.

II. To evaluate the anti-tumor and immunomodulatory effects of mogamulizumab in the CTCL microenvironment in skin and blood samples of erythrodermic CTCL patients.

III. To evaluate the immunomodulatory effects of ECP.

OUTLINE:

Patients receive mogamulizumab intravenously (IV) over 60 minutes on days 1, 8, 15, 22, of cycle 1 and days 1 and 15 of subsequent cycles. Beginning in cycle 2, patients also undergo ECP over 3 hours on days 8, 9, 22,and 23. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR)/partial response (PR) after 6 cycles receive up to 6 additional cycles of treatment in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then for up to 12 months.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Combination Extracorporeal Photopheresis (ECP) and Mogamulizumab in Erythrodermic CTCL
Estimated Study Start Date : October 15, 2021
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2023


Arm Intervention/treatment
Experimental: Treatment (ECP, mogamulizumab)
Patients receive mogamulizumab IV over 60 minutes on days 1, 8, 15, 22, of cycle 1 and days 1 and 15 of subsequent cycles. Beginning in cycle 2, patients also undergo ECP over 3 hours on days 8, 9, 22,and 23. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients achieving CR)/PR after 6 cycles receive up to 6 additional cycles of treatment in the absence of disease progression or unacceptable toxicity.
Procedure: Extracorporeal Photopheresis
Undergo ECP
Other Names:
  • Extracorporeal Photophoresis
  • photopheresis
  • Photophoresis

Biological: Mogamulizumab
Given IV
Other Names:
  • 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

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: Up to 1 year post treatment ]
    ORR will be calculated as the proportion of evaluable patients that have confirmed complete response (CR) or partial response (PR), as defined according to global response assessment. Exact 95% confidence intervals will be calculated for these estimates.

  2. Incidence of adverse events [ Time Frame: Up to cycle 3 (each cycle = 28 days) ]
    Toxicity and adverse events will be recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 scale. Observed toxicities will be summarized by type, severity, date of onset, and attribution.


Secondary Outcome Measures :
  1. Complete response rate [ Time Frame: Up to 1 year post treatment ]
    Defined as the proportion of response-evaluable patients that have a documented CR.

  2. Time to response [ Time Frame: From initiation of study therapy to the first achievement of CR or PR, assessed up to 1 year ]
    Will be estimated using the product-limit method of Kaplan and Meier.

  3. Duration of response [ Time Frame: From the first achievement of PR or CR to time of partial disease or death, assessed up to 1 year ]
    Will be estimated using the product-limit method of Kaplan and Meier.

  4. Progression-free survival [ Time Frame: From initiation of study therapy to the first observation of disease relapse/progression or death from any cause, whichever occurs first, assessed up to 1 year ]
    Will be estimated using the product-limit method of Kaplan and Meier.

  5. Overall survival [ Time Frame: From initiation of study therapy to death from any cause, assessed up to 1 year ]
    Will be estimated using the product-limit method of Kaplan and Meier.

  6. Incidence of adverse events [ Time Frame: Up to 30 days post treatment ]
    Toxicity and adverse events will be recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 scale. Observed toxicities will be summarized by type, severity, date of onset, and attribution.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

    • Assent, when appropriate, will be obtained per institutional guideline
  • 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) =< 2
  • Histologically confirmed mycosis fungoides (MF) or Sezary syndrome (SS). Safety lead-in: >= stage IIB OR >= stage IB-IIA folliculotropic/transformed MF. Phase 2: >= stage IB

    • 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 of Cutaneous Lymphomas (ISCL) should be used.
  • Measurable disease per Modified Severity Weighted Assessment Tool (mSWAT) and/or Sezary count
  • Baseline skin biopsy taken within 6 months available for central review submission
  • Without bone marrow involvement: Absolute neutrophil count (ANC) >= 1,500/mm^3 (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

    • NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
  • With bone marrow involvement: ANC >= 1,000/mm^3 (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

    • NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
  • Without bone marrow involvement: Platelets >= 100,000/mm^3 (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

    • NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
  • With bone marrow involvement: Platelets >= 75,000/mm3 (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)

    • NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless has Gilbert's disease)(performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)
  • Aspartate aminotransferase (AST) =< 2.5 x ULN (unless has Gilbert's disease)(performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)
  • Alanine aminotransferase (ALT) =< 2.5 x ULN (unless has Gilbert's disease)(performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)
  • Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (unless has Gilbert's disease) (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)
  • If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) =< 1.5 x ULN (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)
  • If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)
  • If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)
  • If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (performed within 7 days prior to day 1 of protocol therapy unless otherwise stated)
  • Hepatitis C virus (HCV)*, active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR])

    • If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed
  • Meets other institutional and federal requirements for infectious disease titer requirements

    • Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
  • Subjects with MF and a history of staphylococcus colonization are eligible provided they continue to receive stable doses of prophylactic antibiotics
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy

    • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

  • Prior mogamulizumab
  • Any systemic therapy, including monoclonal antibody within 28 days or 5 half-lives (whichever is shorter) of initiating protocol therapy
  • Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy
  • Any skin-directed therapy within 14 days prior to initiating protocol therapy
  • Any radiation therapy within 21 days prior to initiating protocol therapy
  • Immunosuppressive medication within 14 days prior to the first dose of study treatment. The following are exceptions to this criterion:

    • Intranasal, inhaled, topical or local steroid injections (e.g., intra-articular injection) and are on stable dose for at least 28 days
    • Systemic corticosteroids at physiologic doses of < 10 mg/day of prednisone or equivalent
  • Live, attenuated vaccine within 30 days prior to the first dose protocol therapy
  • Disease free of prior malignancies for >= 5 years with the exception of:

    • Currently treated squamous cell and basal cell carcinoma of the skin, or
    • Carcinoma in situ of the cervix, or
    • Surgically removed melanoma in situ of the skin (stage 0) with histological confirmed free margins of excision, or
    • Prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) that has/have been surgically cured, or
    • Any other malignancy that has/have been curatively treated with surgery and/or localized radiation
  • Active infection requiring antibiotics
  • Known hepatitis B or hepatitis C infection
  • Other active malignancy
  • Females only: Pregnant or breastfeeding
  • Prior stem cell transplantation
  • Acute infection requiring systemic treatment
  • Conditions requiring chronic steroid or immunosuppressive treatment that likely need additional steroid or immunosuppressive treatments in addition to the protocol therapy
  • Renal failure requiring hemodialysis or peritoneal dialysis
  • 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
  • Major surgery (as defined by the investigator) within the 28 days prior to the first dose of study treatment
  • Active or prior documented autoimmune or inflammatory disorders requiring therapy within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:

    • Vitiligo or alopecia
    • Hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; or
    • Psoriasis not requiring systemic treatment
  • History of primary immunodeficiency
  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04930653


Locations
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United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Contact: Farah R. Abdulla    626-218-5822    fabdulla@coh.org   
Principal Investigator: Farah R. Abdulla         
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Farah R Abdulla City of Hope Medical Center
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Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT04930653    
Other Study ID Numbers: 20724
NCI-2021-03533 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
20724 ( Other Identifier: City of Hope Medical Center )
P30CA033572 ( U.S. NIH Grant/Contract )
First Posted: June 18, 2021    Key Record Dates
Last Update Posted: August 12, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Mycoses
Lymphoma
Mycosis Fungoides
Sezary Syndrome
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Syndrome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes
Lymphoma, Non-Hodgkin
Bacterial Infections and Mycoses
Infections
Mogamulizumab
Immunoglobulins
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents