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Mycosis FungoidesPhase 1/2NCT04676087

Mogamulizumab and Extracorporeal Photopheresis for the Treatment of Sezary Syndrome or Mycosis Fungoides

A Phase 1/2 study testing Extracorporeal Photopheresis, Mogamulizumab and Quality-of-Life Assessment in people with Mycosis Fungoides and Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, run by Emory University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase Ib/II trial investigates the side effects of mogamulizumab and extracorporeal photopheresis and to see how well they work in treating patients with Sezary syndrome or mycosis fungoides. Mogamulizumab (a humanized antibody) binds to CCR4, a protein often found in high amounts on T-cell lymphoma cells. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Extracorporeal Photopheresis, Mogamulizumab and Quality-of-Life Assessment
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
21 Apr 2021to 11 Oct 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Histopathologic diagnosis of primary cutaneous T-cell non-Hodgkin lymphoma (CTCL) (mycosis fungoides [MF] or Sezary syndrome [SS]), confirmed by skin biopsy, or lymph node, or blood assessment, of current disease
  • CTCL stage 3A-4A2 disease at study entry according to International Society of Cutaneous Lymphoma (ISCL)/European Organization for Research and Treatment of Cancer (EORTC)
  • Newly diagnosed or =< 3 different lines of systemic therapy
  • Systemic therapy includes oral retinoids, interferon, pralatrexate, methotrexate, vorinostat, romidepsin, single or multi-agent chemotherapy or other oral, IV or subcutaneous treatments used to treat systemic disease
  • A line of therapy is defined as any therapy or group of therapies that was started or changed for lack of response, disease progression, or intolerance
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  • Prior cytotoxic chemotherapy excluding low dose methotrexate
  • A minimum washout period of 4 weeks after previous CTCL therapy is recommended prior to the first dose of combination therapy
  • Willing and able to comply with all aspects of the protocol
  • Provide voluntary written informed consent prior to any study specific screening procedures
  • Absolute neutrophil count (ANC) >= 500/mcL (within 16 days of cycle 1 day 1)
  • Platelets >= 50,000/mcL (within 16 days of cycle 1 day 1)
  • Total bilirubin =< 3 institutional upper limit of normal (ULN) (within 16 days of cycle 1 day 1)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 5 institutional upper limit of normal (ULN) (within 16 days of cycle 1 day 1)
  • Not dialysis dependent, creatinine clearance >= 30 mL/min (within 16 days of cycle 1 day 1)
  • Female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy: documented by negative beta-human chorionic gonadotropin [beta-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of beta-hCG. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug
  • FCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 30 Days after completion. 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 30 days after completion of study drug administration. A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months

Who cannot join

  • Visceral involvement except for CTCL involvement of the bone marrow
  • Bulky lymphadenopathy (> 5 cm), or pathologically N3 lymph node involvement
  • Total skin electron beam therapy within 6 months prior to registration
  • Prior allogeneic transplantation
  • Prior mogamulizumab therapy within 6 months of registration or progression or intolerance of mogamulizumab
  • Patients with 2 or less doses of prior mogamulizumab prior to registration will be eligible regardless of date mogamulizumab was received
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  • Patients who received mogamulizumab pre-study enrollment would restart day 1 dosing per protocol
  • Prior ECP > 2 months in duration within 3 months of registration
  • Patients with ECP treatment prior to registration will be eligible regardless of date ECP was received (as long as it was not > 2 months in duration within the 3 months immediately prior to registration), as long as they have measurable disease at the time of enrollment
  • Use of topical steroids within 14 days of day 1 of initial therapy is not allowed, with the following exception:
  • Topical steroids or systemic low dose steroids (=< 10 mg/day prednisone) are allowed in subjects with erythroderma who have been on corticosteroids for a prolonged period of time and where discontinuation may lead to rebound flare in disease. The concomitant steroid medication is allowed as long as the type of steroid, route of administration, and steroid dose remain the same as what the subject had been receiving for a prolonged period of time
  • Severe or uncontrolled autoimmune condition
  • Active, life threatening malignancy (except for CTCL, definitively treated basal or squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix, or other localized malignancies treated with curative intent with surgery or radiation alone) within the past 12 months
  • Serious intercurrent illness
  • Known significant cardiac disease requiring ongoing treatment, including congestive heart failure (CHF), severe coronary artery disease (CAD), cardiomyopathy, uncontrolled cardiac arrhythmia, unstable angina pectoris, or myocardial infarction (MI) (within 6 months of study enrollment)
  • Major surgery within 2 weeks of study enrollment
  • Significant or uncontrolled infections requiring systemic anti-infective therapy
  • Patients with human immunodeficiency virus (HIV) infection are eligible. Patients with HIV infection must meet the following: No evidence of co-infection with hepatitis B or C; CD4+ count > 400/mm; no evidence of resistant strains of HIV; on anti-HIV therapy with an HIV viral load < 50 copies HIV RNA/mL. Patients with HIV must have ongoing follow-up with an infectious disease specialist and must have been evaluated within 90 days of cycle 1 day 1
  • Patients with a history of hepatitis C are eligible as long as the hepatitis C has been treated and cleared and they have no evidence of hepatic dysfunction related to hepatitis C. Patients must have been seen by a hepatologist within 6 months of cycle 1 day 1
  • Patients who test positive for hepatitis B core antibody may enroll on the study as long as they test negative for both hepatitis B surface antigen and hepatitis B deoxyribonucleic acid (DNA), and if they have no evidence of hepatic dysfunction that is felt to be related to hepatitis B
  • Patients may not have an auto-immune disease requiring systemic immunosuppression, biologic therapy, and/or steroid use (>= 10 mg daily of prednisone or equivalent)
  • Patients will not be excluded based on CCR4 expression
  • Females who are pregnant (positive urine test) or breastfeeding

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Emory University Hospital

    Atlanta, Georgia, 30322

Other trials in United States

About this study

Official title: Mogamulizumab and Extracorporeal Photopheresis (ECP) for the Treatment of Sézary Syndrome and Erythrodermic Mycosis Fungoides, a Phase 1b/2 Study

This phase Ib/II trial investigates the side effects of mogamulizumab and extracorporeal photopheresis and to see how well they work in treating patients with Sezary syndrome or mycosis fungoides. Mogamulizumab (a humanized antibody) binds to CCR4, a protein often found in high amounts on T-cell lymphoma cells. Binding to these cells may slow their growth, as well as mark them for attack by the immune system. Extracorporeal photopheresis (ECP) is a standard treatment for cancers that affects the skin, and may work by killing some lymphoma cells directly and by boosting the body's immune response against other lymphoma cells. Giving mogamulizumab together with ECP may work better in treating patients with Sezary syndrome or mycosis fungoides compared to either therapy alone.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the safety and tolerability of the combination of mogamulizumab and ECP in Sezary syndrome (SS) and erythrodermic mycosis fungoides (MF).

II. To determine the efficacy of the combination of mogamulizumab and extra-corporeal photopheresis in SS and erythrodermic MF.

SECONDARY OBJECTIVE:

  1. To assess response by disease compartment, time to response, duration of response, progression free survival (PFS), and change in quality of life in patients with Sezary syndrome and erythrodermic MF treated with mogamulizumab and ECP.

TERTIARY/EXPLORATORY OBJECTIVE:

  1. To assess biomarkers of response and changes in immunologic response on serial blood samples and peripheral blood flow cytometry.

OUTLINE:

INDUCTION (WEEKS 1-7): Patients receive mogamulizumab intravenously (IV) over 60 minutes on days 1, 8, 15, 22, and 36 in the absence of disease progression progression and unacceptable toxicity. Patients also undergo extracorporeal photopheresis on days 1, 8, 15, 22, 29, and 36 in the absence of disease progression and unacceptable toxicity.

TREATMENT (CYCLES 1-12): Patients receive mogamulizumab IV over 60 minutes on days 1 and 15, and undergo extracorporeal photopheresis on days 1 and 15 of cycles 1-6, then day 1 of subsequent cycles. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression and unacceptable toxicity.

MAINTENANCE (CYCLES 13+): Patients with clinical benefit may continue extracorporeal photopheresis on day 1. Cycles repeat every 28 days in the absence of disease progression and unacceptable toxicity.

After completion of study treatment, patients are followed up for 90 days, then every 3 months for 3 years.

Being tested
Extracorporeal Photopheresis, Mogamulizumab, Quality-of-Life Assessment
Medical subject headings
Mycosis Fungoides, Lymphoma, T-Cell, Cutaneous, Sezary Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Extracorporeal PhotopheresisProcedure or surgery

    Also called Extracorporeal Photophoresis, photopheresis, Photophoresis

    Undergo ECP

  • MogamulizumabBiological

    Also called 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

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

Study groups in NCT04676087
Study groupRoleWhat they receive
Treatment (mogamulizumab, ECP)ExperimentalINDUCTION (WEEKS 1-7): Patients receive mogamulizumab IV over 60 minutes on days 1, 8, 15, 22, and 36 in the absence of disease progression progression and unacceptable toxicity. Patients also undergo extracorporeal photopheresis on days 1, 8, 15, 22, 29, and 36 in the absence of disease progression and unacceptable toxicity. TREATMENT (CYCLES 1-12): Patients receive mogamulizumab IV over 60 minutes on days 1 and 15, and undergo extracorporeal photopheresis on days 1 and 15 of cycles 1-6, then day 1 of subsequent cycles. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression and unacceptable toxicity. MAINTENANCE (CYCLES 13+): Patients with clinical benefit may continue extracorporeal photopheresis on day 1. Cycles repeat every 28 days in the absence of disease progression and unacceptable toxicity.
Receives: Procedure: Extracorporeal Photopheresis; Biological: Mogamulizumab; Other: Quality-of-Life Assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency of dose-limiting toxicities (DLT's) (Phase Ib)

    Descriptive statistics (n, frequency and percentage) of toxicities and number of DLT's during the DLT window per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be reported. Corresponding listings of data will be generated. DLT rate will be calculated as proportion (Patients with DLT/Total patients) along with 95% confidence intervals using the Clopper-Pearson method.

    Measured: Up to 6 weeks

  2. Rate of overall response lasting at least 6 months (ORR6) (Phase II)

    Assessed using the Global Response Score (GRS). ORR6 rate will be determined by dividing the number of ORR6's by the total number of evaluable patients. Will be calculated as proportion (Responders/Total patients) along with 95% confidence intervals using the Clopper-Pearson method. Chi-square test or Fisher's exact test will be used to compare the efficacy in term of response rate between the different groups stratified by baseline factors, respectively. Logistic regression model will be further employed to test the adjusted effect of dosage on the response rate after adjusting for other clinical factors and demographic factors.

    Measured: Up to 3 years post treatment

Secondary outcomes (6)

  1. Best overall response rate (ORR)

    Assessed using the Global Response Score (GRS), which consists of skin evaluation (modified severity weighted assessment tool [mSWAT]), radiographic assessment, and detection of circulating Sezary cells on flow cytometry in patients that have received at least 1 month of combined therapy. Overall response, complete response, and partial response will be calculated as proportions along with 95% confidence intervals using the Clopper-Pearson method.

    Measured: Up to 3 years post treatment

  2. Duration of response (DOR)

    Based on GRS. Defined as time from the date when criteria for response (complete response [CR] or partial response [PR]) based on GRS was first met until the date when the response was first lost (date of loss is date when first meets criteria for progressive disease [PD] or death). Will be estimated using the Kaplan-Meier method.

    Measured: Up to 3 years post treatment

  3. Time to response (TTR)

    Based on GRS. Defined as time from the date of first dosing to the date when criteria for response (CR or PR) based on GRS are first met. Will be estimated using the Kaplan-Meier method.

    Measured: Up to 3 years post treatment

  4. Overall survival (OS)

    Estimated by Kaplan-Meier method. Cox proportional hazards models will be further used in the multivariable analyses to assess the patients' OS after adjusting for other factors. Interaction terms between these factors will also be tested for statistical significance. The proportional hazards assumption will be evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions will be addressed by use of time-dependent covariates or extended Cox regression models.

    Measured: Date of 1st dose of study drug to death from any cause, assessed up to 3 years

  5. Progression free survival (PFS)

    Estimated by Kaplan-Meier method. Cox proportional hazards models will be further used in the multivariable analyses to assess the patients' PFS after adjusting for other factors. Interaction terms between these factors will also be tested for statistical significance. The proportional hazards assumption will be evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions will be addressed by use of time-dependent covariates or extended Cox regression models.

    Measured: Date of 1st dose of study drug to progression, death, or subsequent systemic anti-cancer therapy, assessed up to 3 years

  6. Incidence of adverse events

    Adverse events (AEs) will be listed and summarized. Adverse events will also be listed by severity, seriousness, and by system organ class. Will also evaluate toxicities which will be presented in tabular form as appropriate based on grade and attribution. The number and percentage of subjects who experience AEs will be presented in tabular and/or graphical format and summarized descriptively, where appropriate AEs will be presented with and without regard to causality based on the investigator's judgment. The frequency of overall toxicity, categorized by toxicity grades 1 through 5, will be described. Additional summaries will be provided for AEs that are observed with higher frequency.

    Measured: Up to 3 years post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Dec 2020
  2. Study start21 Apr 2021
  3. Primary completion11 Oct 2023
  4. Study completion11 Oct 2023

Why it stopped: Lack of funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04676087
Sponsor's protocol ID
STUDY00001265
Other IDs
NCI-2020-06013, WINSHIP5101-20, P30CA138292
Status last verified
Aug 2024
First submitted
9 Nov 2020
Last updated
13 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Extracorporeal Photopheresis, Mogamulizumab and Quality-of-Life Assessment in people with Mycosis Fungoides and Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, run by Emory University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Lack of funding). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of dose-limiting toxicities (DLT's) (Phase Ib) (time frame: Up to 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04676087.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2024.

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