Clinical Trials /

A Study to Assess the Feasibility of Romidepsin Combined With Brentuximab Vedotin in Cutaneous T-cell Lymphoma

NCT02616965

Description:

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.

Related Conditions:
  • Hematopoietic and Lymphoid System Neoplasm
  • Mycosis Fungoides
  • Sezary Syndrome
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Assess the Feasibility of Romidepsin Combined With Brentuximab Vedotin in Cutaneous T-cell Lymphoma
  • Official Title: A Phase I Trial Assessing the Feasibility of Romidepsin Combined With Brentuximab Vedotin for Patients With Requiring Systemic Therapy for Cutaneous T-cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: HM-085
  • NCT ID: NCT02616965

Conditions

  • Cutaneous T-cell Lymphoma (CTCL)

Interventions

DrugSynonymsArms
RomidepsinTreatment
Brentuximab vedotinTreatment

Purpose

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.

Detailed 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.
    

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalTreatment consists of the combination of Romidepsin given 10mg/m2 or 14mg/m2 on days 1, 8 and 15 every 28 days and Brentuximab vedotin given 0.9mg/kg or 1.2mg/kg on days 1 and 15 every 28 days for 16 cycles.
  • Romidepsin
  • Brentuximab vedotin

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD)
Time Frame:during treatment period which is an average of 64 weeks.
Safety Issue:
Description:CTCAE v4.03

Secondary Outcome Measures

Measure:overall safety and tolerability of the combination of brentuximab vedotin & romidepsin assessed by adverse events.
Time Frame:from start of treatment to 30 days post treatment period (16 cycles)
Safety Issue:
Description:CTCAE v4.03
Measure:Estimate complete and partial response rate of the combination treatment
Time Frame:64 weeks, 30 days post treatment and every 12 weeks post-treatment, up to 2 years
Safety Issue:
Description:mSWAT skin assessment
Measure:Estimate complete and partial response rate of the combination treatment
Time Frame:64 weeks, 30 days post treatment and every 12 weeks post-treatment, up to 2 years
Safety Issue:
Description:Global Response Score (GRS).
Measure:Overall survival (OS)
Time Frame:From the time of patient registration until death, measured every 12 weeks up to 2 years
Safety Issue:
Description:OS is measured by length of time
Measure:Progression free survival (PFS)
Time Frame:From the time of patient registration until disease progression, measured every 12 weeks up to 2 years
Safety Issue:
Description:PFS is measured in length of time by RECIST v1.1

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fox Chase Cancer Center

Last Updated