Phase I Dose-finding and Preliminary Efficacy Study of the Istodax® in Combination With Doxil® for the Treatment of Adults With Relapsed or Refractory Cutaneous T-cell Lymphoma

NCT01902225 | Completed Phase 1 DMC

• 2 other identifiers: 112516NCI-2014-01722
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

This a multi-center, single arm, open-label, Phase I dose-finding and preliminary efficacy study of the combination of the histone deacetylase inhibitor romidepsin (Istodax®) in combination with doxorubicin HCl liposomal (Doxil®) for adult patients with relapsed or refractory cutaneous T-cell lymphoma after at least 2 lines of skin-directed therapy or one prior line of systemic therapy. Patients will be treated with Doxil 20mg/m2 on day 1 and romidepsin 8-14mg/m2 on days 1, 8 and 15, every 28 days, until 2 cycles beyond the best response, 8 cycles, disease progression or intolerability whichever comes first. Importantly, doxil is administered prior to romidepsin on day1 of each cycle. Patients will be followed until disease progression or death whichever comes first.

Conditions

Lymphoma; T-Cell Lymphoma; Cutaneous Lymphoma

Keywords

Lymphoma; T-Cell; Cutaneous; Doxil; romidepsin; skin

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  The maximum tolerated dose (MTD) will be defined as the highest tested dose level where 33% or more participants experience a dose limiting toxicity (DLT)

  Up to 2 years

Secondary Outcomes (8)

• Complete response (CR) rate

  Up to 2 years

• Overall response rate (CR + PR)

  Up to 2 years

• Time to response (TTR)

  Up to 2 years

• Duration of response (DOR)

  Up to 2 years

• Time to progression (TTP)

  Up to 2 years

Study Arms (1)

Istodax, Doxil

EXPERIMENTAL

Istodax; Intravenous; 8-14 mg/m2; Days 1, 8, and 15; over 4 hours Doxil; Intravenous; 20 mg/m2; Day 1; over 1 hour

Drug: Istodax; Drug: Doxil

Interventions

Istodax DRUG

Also known as: Romidepsin

Istodax, Doxil

Doxil DRUG

Also known as: Liposomal doxorubicin

Istodax, Doxil

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and voluntarily sign an informed consent form.
• Age ≥18 years at the time of signing the informed consent form.
• Able to adhere to the study visit schedule and other protocol requirements.
• Biopsy-proven, measurable, Stage IB-IVB relapsed or refractory cutaneous T-cell lymphoma after 2 lines of skin-directed therapy or one prior line of systemic therapy (Note: extracorporeal photopheresis will be considered a systemic therapy for this study)
• All cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study. The only exceptions are participants with erythroderma who have been on corticosteroids for prolonged periods of time (\>60 days) without change may continue use of either low dose systemic steroid (equivalent to \<10 mg per day of prednisone) or low potency topical steroids are eligible for this study if the frequency and dosage steroids has not changed for 60 days prior to the study. These participants should continue on the same dose of systemic/topical steroid throughout the study period unless they achieve a complete response at which time steroids can be discontinued. Patients are allowed to continue any medications with known activity in T cell lymphomas at the pre-enrollment doses for conditions other than T cell lymphomas (ie, steroids for sarcoidosis) , as long as there is evidence of T cell lymphoma progression while patients were on these agents.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry.
• Laboratory test results within these ranges:
• Absolute neutrophil count ≥750/mm³
• Platelet count≥75,000/mm³
• Total bilirubin ≤ 2 x upper limit of normal (ULN)
• ULN and Aspartate Aminotransferase (ALT) (SGPT) ≤ 3 x ULN.
• Creatinine \< 2 mg/dL
• Disease free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast. Patients with early stage of prostate cancer under clinical surveillance without therapy are eligible
• Negative serum pregnancy test at the time of enrollment for females of childbearing potential.
• For males and females of child-producing potential, use of effective contraceptive methods during the study to include 2 methods of contraception, one being a condom.

You may not qualify if:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or breast feeding females.
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Use of any other experimental drug or therapy within 28 days of baseline except topical therapy for mycosis fungoides which must be discontinued 14 days prior to initiation of study therapy.
• Prior allogeneic hematopoietic cell transplant.
• Prior solid organ transplant.
• Cumulative anthracycline exposure greater than 300 mg/m2 doxorubicin equivalents.
• Known active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of prior hepatitis B virus vaccination are eligible.
• Central nervous system or meningeal involvement
• Any known cardiac abnormalities including:
• Congenital long QT syndrome
• Baseline QTc interval ≥ 480 milliseconds;
• Myocardial infarction within 6 months of Cycle 1 Day 1 (C1D1). Subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate
• Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
• Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II- IV. In any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present

Sponsors & Collaborators

• Weiyun Ai: lead
• Celgene Corporation: collaborator

Study Sites (2)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous

Interventions

romidepsin; liposomal doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin

Study Officials

• Ai Wei, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: July 15, 2013
• First Posted: July 18, 2013
• Study Start: March 4, 2014
• Primary Completion: July 13, 2018
• Study Completion: April 11, 2020
• Last Updated: June 9, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)