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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT02616965
Other study ID # HM-085
Secondary ID 16-1009
Status Active, not recruiting
Phase Phase 1
First received
Last updated
Start date February 22, 2017
Est. completion date December 2024

Study information

Verified date February 2024
Source Fox Chase Cancer Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a Phase I Trial to assess the feasibility of Romidepsin combined with Brentuximab Vedotin for patients requiring Systemic Therapy for Cutaneous T-cell Lymphoma.


Description:

This is a traditional "3+3" phase 1 dose de-escalation design testing up to 3 dose levels of romidepsin in conjunction with brentuximab vedotin in patients with untreated or previously treated (up to 2 prior systemic regimens, including photopheresis) CTCL. Dose-limiting toxicities (DLT) will be determined during cycle 1. The first 3 subjects will begin at dose level 1. If no DLT is encountered another 3 subjects will be enrolled at the same dose level. The maximum tolerated dose (MTD) will be the dose level at which ≤ 1 of 6 of subjects experience DLT. If more than one subject at any one dose level encounters a DLT, the dose will be de-escalated for all subsequent subjects. Should no DLTs occur, the investigators will not escalate beyond dose level 1. Once the MTD has been confirmed, the investigators will enroll an additional 9 patients in a toxicity refinement cohort for a total of 15 evaluable patients at the MTD. Treatment will continue for up to 16 cycles (one cycle is 28 days) or until disease progression or toxicities, whichever occurs first. Drugs can be continued after 16 cycles if a patient has derived a clinical benefit from treatment after discussion with the sponsor-investigator.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 16
Est. completion date December 2024
Est. primary completion date February 20, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Patients must have histologically or cytologically confirmed diagnosis of mycosis fungoides (MF), Sezary syndrome (SS) or primary cutaneous CD30-positive lymphoproliferative disorder, including lymphomatoid papulosis and primary cutaneous ALCL (pc-ALCL)as defined by the WHO classification of Tumors of Hematopoietic and Lymphoid tissue. Please note that tumor samples for patients with MF or SS can be CD30 negative and do not have to be CD30 positive on either flow cytometry or immunohistochemistry for patients to be eligible. 2. Patients with MF/SS must have stage IB, IIA, IIB, III or IV disease; patients with primary cutaneous CD30-positive lymphoproliferative disorder must have multifocal symptomatic or extensive lesions requiring systemic treatment. 3. Patients must require systemic treatment. 4. Patients can have received up to 2 lines of systemic treatment. Psoralen plus ultraviolet light therapy (PUVA) is not considered to be a systemic therapy. 5. Age > 18 years. 6. ECOG performance status 0, 1 or 2. 7. Patients must have acceptable organ and marrow function as defined below: - Absolute neutrophil count > 1,500/mcL - Platelets > 100,000/mcL - Total bilirubin within normal institutional limits - AST/ALT (SGOT/SGPT) < 2 times institutional normal limits - Creatinine within normal institutional limits OR - Creatinine clearance > 60 Ml/min/1.73 m2 for patients with creatinine levels above institutional normal 8. Women of child-bearing potential (WOCBP) must have a negative pregnancy test 9. Ability to understand and willingness to sign a written informed consent and HIPAA consent document. 10. Patients with HIV who are not receiving cytochrome p450 inhibitors, and who have a minimum of 300+ CD4+ cells/mm3, an undetectable viral load, and no history of AIDS indicator conditions. Exclusion Criteria: 1. Patients who have not had resolution of clinically significant toxic effects of prior anticancer therapy to =grade 1 as per by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE, v.4.0). 2. Grade 2 or greater neuropathy. 3. Patients may not be receiving any other investigational agents. 4. Patients with known CNS involvement. 5. Patients must not receive concurrent systemic or topical steroids or other skin directed therapy while on study except as outlined in 5.2.2 6. Patients who have experienced allergic reactions to monoclonal antibodies. 7. Patients who have received prior HDAC inhibitors, or brentuximab vedotin, except for patients who were exposed to above drugs only for a short time (less than 8 weeks), did not progress while on treatment, and did not have intolerable toxicity but were discontinued for another reason (e.g., comorbidity) may be permitted to enter the study after discussion with the sponsor-investigator. 8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 9. Pregnant or breast feeding. Refer to section 4.4 for further detail. 10. Second malignancies that require active treatment with the exception of breast or prostate cancer on endocrine therapy.

Study Design


Intervention

Drug:
Romidepsin
Romidepsin at the dosage 10mg/m2 or 14mg/m2 will be given ONCE 14 days prior to cycle one and then on days 1,8,15 in each cycle. Each cycle is 28 days and treatment will continue up to 16 cycles
Brentuximab vedotin
Brentuximab vedotin at the dosage 0.9mg/kg or 1.2 mg/kg will be given on days 1 and 15 in each cycle. Each cycle is 28 days and treatment will continue up to 16 cycles

Locations

Country Name City State
United States Fox Chase Cancer Center Philadelphia Pennsylvania
United States University of Pennsylvania, Perelman Center Philadelphia Pennsylvania

Sponsors (3)

Lead Sponsor Collaborator
Fox Chase Cancer Center Celgene Corporation, Seagen Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum tolerated dose (MTD) CTCAE v4.03 during treatment period which is an average of 64 weeks.
Primary Dose-limiting toxicities (DLTs) CTCAE v4.03 during the first 28 days (cycle 1) of treatment
Secondary overall safety and tolerability of the combination of brentuximab vedotin & romidepsin assessed by adverse events. CTCAE v4.03 from start of treatment to 30 days post treatment period (16 cycles)
Secondary Estimate complete and partial response rate of the combination treatment mSWAT skin assessment 64 weeks, 30 days post treatment and every 12 weeks post-treatment, up to 2 years
Secondary Estimate complete and partial response rate of the combination treatment Global Response Score (GRS). 64 weeks, 30 days post treatment and every 12 weeks post-treatment, up to 2 years
Secondary Overall survival (OS) OS is measured by length of time From the time of patient registration until death, measured every 12 weeks up to 2 years
Secondary Progression free survival (PFS) PFS is measured in length of time by RECIST v1.1 From the time of patient registration until disease progression, measured every 12 weeks up to 2 years
See also
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Active, not recruiting NCT02213861 - Efficacy, Safety and Tolerability Study of SHAPE in IA, IB or IIA Cutaneous T-cell Lymphoma Phase 2
Recruiting NCT05225584 - Safety, PK, PD, Clinical Activity of KT-333 in Adult Patients With Refractory Lymphoma, Large Granular Lymphocytic Leukemia, Solid Tumors Phase 1
Completed NCT00611208 - A-dmDT390-bisFv(UCHT1) Immunotoxin Therapy for Patients With Cutaneous T-Cell Lymphoma (CTCL) Phase 2
Completed NCT02580552 - Safety, Tolerability and Pharmacokinetics of MRG-106 in Patients With Mycosis Fungoides (MF), CLL, DLBCL or ATLL Phase 1
Terminated NCT02314247 - Efficacy and Safety Study of Selinexor in Relapsed or Refractory Peripheral T-cell Lymphoma or Cutaneous T-cell Lymphoma Phase 2
Withdrawn NCT01843998 - Therapeutic Efficacy of Topical Sirolimus in Early Stage Cutaneous T-cell Lymphoma (CTCL) Phase 2
Terminated NCT00476554 - A Randomized Phase II Study of Oral Sapacitabine in Patients With Advanced Cutaneous T-cell Lymphoma Phase 2