Dosing of Brentuximab Vedotin for Mycosis Fungoides, Sezary Syndrome Patients

Optimizing Dosing of Brentuximab Vedotin for Mycosis Fungoides, Sezary Syndrome, and Lymphomatoid Papulosis

The purpose of this study is to test any good and bad effects of the study drug called brentuximab vedotin at a lower dose than is FDA-approved.

Study Overview

• Status: Recruiting
• Conditions: Mycosis Fungoides; Sezary Syndrome; Lymphomatoid Papulosis
• Intervention / Treatment: Drug: brentuximab vedotin; Drug: brentuximab vedotin; Drug: brentuximab vedotin

• Study Type: Interventional
• Enrollment (Estimated): 58
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Patricia Myskowski, MD; Phone Number: 646-608-2351
• Study Contact Backup: Name: Alison Moskowitz, MD; Phone Number: 646-608-3726; Email: moskowia@mskcc.org

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305-5408
      • Recruiting
      • Stanford University Medical Center
      • Contact: Youn Kim, MD; Phone Number: 650-498-6000
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge
      • Contact: Alison Moskowitz, MD; Phone Number: 646-608-3726
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth
      • Contact: Alison Moskowitz, MD; Phone Number: 646-608-3726
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen
      • Contact: Alison Moskowitz, MD; Phone Number: 646-608-3726
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Commack
      • Contact: Alison Moskowitz, MD; Phone Number: 646-608-3726
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester
      • Contact: Alison Moskowitz, MD; Phone Number: 646-608-3726
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Patricia Myskowski, MD; Phone Number: 646-608-2351
      • Contact: Alison Moskowitz, MD; Phone Number: 646-608-3726
      • Principal Investigator: Alison Moskowitz, MD
    • Uniondale, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau
      • Contact: Alison Moskowitz, MD; Phone Number: 646-608-3726

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Mycosis fungoides (MF) and Sezary Syndrome (SS)

1. Pathologically confirmed mycosis fungoides/sezary syndrome at the enrolling institution, disease stage IB (defined as patches, plaque, or papules that involve 10% of the skin surface viscera) or higher

   ° CD30 negative mycosis fungoides patients are eligible.

2. Age ≥ 18 years
3. ECOG Performance Score ≤ 2
4. For Cohort 1, patients who have not received brentuximab vedotin are eligible.
5. For Cohort 2, patients who have previously had brentuximab vedotin for MF/SS are eligible. Patients previously treated on Cohort 1 who were discontinued due to toxicity are not eligible for Cohort 2.

6. Previous systemic anti-cancer therapy must have been discontinued at least 2 weeks prior to treatment.

   ° See section 6.2 Subject Exclusion Criteria for guidelines regarding adjuvant and maintenance therapy for prior malignancy.

7. Topical or systemic steroids (equivalent to ≤ 10 mg/day of prednisone) may be considered if dose has been constant and discontinuation may lead to rebound flare in disease, adrenal insufficiency, and/or unnecessary suffering, after discussion with PI.
8. If HIV+, patient must be on stable anti-retroviral treatment for 12 weeks prior to C1D1, with CD4 count >200 within 7 days prior to C1D1.
9. Females of childbearing potential must be on acceptable form of birth control per instutional standard.

Lymphomatoid papulosis (LyP)

1. Pathologically confirmed lymphomatoid papulosis at the enrolling institution
2. Requiring systemic treatment per investigator's discretion
3. Age ≥ 18 years
4. ECOG Performance Score ≤ 2
5. Previous systemic anti-cancer therapy must have been discontinued at least 2 weeks prior to treatment.
6. Topical or systemic steroids (equivalent to ≤ 10 mg/day of prednisone) may be considered if dose has been constant and discontinuation may lead to rebound flare in disease, adrenal insufficiency, and/or unnecessary suffering.
7. If HIV+, patient must be on stable anti-retroviral treatment for 12 weeks prior to C1D1, with CD4 count >200 within 7 days prior to C1D1.
8. Females of childbearing potential must be on acceptable form of birth control per institutional standard

Exclusion Criteria:

1. Concurrent use of other systemic anti-cancer agents or treatments for mycosis fungoides/sezary syndrome, or lymphomatoid papulosis.
2. Grade 2 or greater neuropathy
3. Severe renal impairment (CrCL <30 mL/min)

4. Moderate or severe hepatic impairment (Child-Pugh B or Child-Pugh C)

   ° See Appendix E for Child Pugh Classification chart

5. Women of reproductive potential† must have a negative Serum ß human chorionic gonadotropin (ß-HCG) pregnancy test within 1 week of C1D1. They should discuss contraception with treating provider.
6. Previous use of brentuximab vedotin (for Cohort 1 ONLY)

7. Receiving systemic therapy for another primary malignancy (other than T-cell lymphoma).

   • Patients with more than one type of lymphoma may be enrolled after discussion with the MSK Principal Investigator.
   • Adjuvant or maintenance therapy to reduce the risk of recurrence of other malignancy (other than T-cell lymphoma) is permissible after discussion with the MSK Principal Investigator.

8. For Cohort 2, patients who previously progressed on the standard 1.8mg/kg dose and schedule of brentuximab vedotin are ineligible.

   • A female of reproductive potential is a sexually mature female who: has not undergone a hysterectomy or bilateral oophorectomy; or 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: not been previously treated with brentuximab vedotin.; Patients with MF/SS who have not been previously treated with brentuximab vedotin. For MF patients: Treatment delays lasting longer than 8 weeks for toxicity will result in removal from study. As of October 2020, the Simon two stage design for Cohort 1 has restarted at the 1.2 mg/kg dose.	Drug: brentuximab vedotin; MF/SS Brentuximab vedotin 0.9 mg/kg 0R 1.2 mg/kg.; Drug: brentuximab vedotin; LyP Brentuximab vedotin 0.9 mg/kg2; Drug: brentuximab vedotin; MF/SS prior brentuximab vedotin-Brentuximab vedotin dose to be determined from Cohort 1
Experimental: treated with reduced dose brentuximab vedotin; Patients with MF/SS who were previously treated with brentuximab vedotin. Up to 10 patients will be enrolled onto this cohort. Following identification of a promising dose after the completion of the full Cohort 1 Simon two stage design, enrollment will initiate onto cohort 2 at the dose found to be promising in cohort 1. For MF patients: Treatment delays lasting longer than 8 weeks for toxicity will result in removal from study. The 0.9mg/kg dose did not meet the primary endpoint for response, therefore 1.2 mg/kg has been chosen as the dose for Cohort 2. As of October 2020, enrollment on our exploratory Cohort 2 has opened at the 1.2 mg/kg dose.	Drug: brentuximab vedotin; MF/SS Brentuximab vedotin 0.9 mg/kg 0R 1.2 mg/kg.; Drug: brentuximab vedotin; LyP Brentuximab vedotin 0.9 mg/kg2; Drug: brentuximab vedotin; MF/SS prior brentuximab vedotin-Brentuximab vedotin dose to be determined from Cohort 1
Experimental: Patients with LyP; Patients with LyP patients with lymphomatoid papulosis will receive brentuximab vedotin 0.9 mg/kg as an intravenous infusion over 30 minutes every three weeks. Cohort 3 will enroll patients concurrently with Cohort 1. Treatment may be held if felt to be in patient's best interest (for example: for toxicity or no active disease). Treatment can be reinitiated after discussion with MSK PI as long as the study is still open and patient has not received alternate systemic therapy.	Drug: brentuximab vedotin; MF/SS Brentuximab vedotin 0.9 mg/kg 0R 1.2 mg/kg.; Drug: brentuximab vedotin; LyP Brentuximab vedotin 0.9 mg/kg2; Drug: brentuximab vedotin; MF/SS prior brentuximab vedotin-Brentuximab vedotin dose to be determined from Cohort 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response	measure best overall response during treatment by the global response score, which incorporates the mSWAT, as well as CT scan for patients with baseline nodal/visceral involvement and flow cytometry for patients with baseline positive peripheral flow cytometry	1 year

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Seagen Inc.
• Investigators: Principal Investigator: Alison Moskowitz, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2018
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: July 3, 2018
• First Submitted That Met QC Criteria: July 3, 2018
• First Posted (Actual): July 16, 2018

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Brentuximab Vedotin; 18-147
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Disease; Bacterial Infections and Mycoses; Lymphoma; Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell; Syndrome; Mycoses; Mycosis Fungoides; Sezary Syndrome; Lymphomatoid Papulosis; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immunoconjugates; Immunotoxins; Antibodies, Monoclonal; Brentuximab Vedotin
• Other Study ID Numbers: 18-147

Drug and device information, study documents

• 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