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
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|ClinicalTrials.gov Identifier: NCT01902225|
Recruitment Status : Active, not recruiting
First Posted : July 18, 2013
Last Update Posted : August 13, 2019
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma T-Cell Lymphoma Cutaneous Lymphoma||Drug: Istodax Drug: Doxil||Phase 1|
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 one prior line of systemic therapy.
MTD will be determined by standard "3+3" dose escalation of romidepsin with a fixed dose of doxorubicin HCl liposomal. Participants will be followed throughout therapy and all adverse events recorded, graded, and given likelihood of relevance to study therapies. Toxicity will be graded by the NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0.
- Response will be assessed by a global response score integrating change in skin disease as measured by the modified severity-weighted assessment tool (mSWAT) score, change in lymph node size, change in visceral disease, and changes in peripheral blood Sézary cells by flow cytometry. CR/PR assignment requires confirmatory assessment in 4 weeks. Skin scores, clinical lymph node, liver and spleen exam, and Sézary cell count assessment will occur on Day 1 of each cycle. Contrasted CT scan of the neck, chest, abdomen and pelvis will be performed at screening for all patients. In patients with lymphadenopathy and/or organomegaly at screening, contrasted CT scans of the neck, chest, abdomen, and pelvis will occur at the end of every third cycle of therapy, within 1 week of cycle 8 completion, and every 6 months for one year after maximal response. All patients will have contrasted CT scans of the neck, chest, abdomen, and pelvis at the time of concern for disease progression in lymph nodes and/or viscera.TTR is the time of the first romidepsin dose to the time of documented objective response (PR/CR). DOR is the time from first objective response (PR or CR) until disease progression.
- TTP will be measured from the time of the first romidepsin dose until disease progression.
- Pruritus will be assessed monthly using a 100 mm visual analog scale. Quality of life will be assessed monthly by Functional Assessment of Cancer Therapy- General (FACT-G), Skindex-29, and ItchyQOL questionnaires.
Skin lesions will be punch biopsied (two contiguous 5mm biopsies) prior to beginning therapy as standard care of care. Any leftover tissue will be collected for research with consent of patient. Optional single 5mm punch biopsies will be obtained on day 15 of Cycle 2 after infusion of romidepsin, and at disease relapse.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter Phase I Dose-finding and Preliminary Efficacy Study of the Histone Deacetylase Inhibitor Romidepsin (Istodax®) in Combination With Doxorubicin HCl Liposomal (Doxil®) for the Treatment of Adults With Relapsed or Refractory Cutaneous T-cell Lymphoma|
|Actual Study Start Date :||March 4, 2014|
|Actual Primary Completion Date :||July 11, 2018|
|Estimated Study Completion Date :||April 1, 2020|
Experimental: Istodax, Doxil
Istodax; Intravenous; 8-14 mg/m2; Days 1, 8, and 15; over 4 hours
Doxil; Intravenous; 20 mg/m2; Day 1; over 1 hour
Other Name: Romidepsin
Other Name: Liposomal doxorubicin
- Maximum Tolerated Dose [ Time Frame: Up to 2 years ]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)
- Complete response (CR) rate [ Time Frame: Up to 2 years ]
- Overall response rate (CR + PR) [ Time Frame: Up to 2 years ]
- Time to response (TTR) [ Time Frame: Up to 2 years ]
- Duration of response (DOR) [ Time Frame: Up to 2 years ]
- Time to progression (TTP) [ Time Frame: Up to 2 years ]
- Changes in degree of pruritus [ Time Frame: Up to 2 years ]
- Quality of life during therapy [ Time Frame: Up to 2 years ]
- Changes in skin related symptoms [ Time Frame: Up to 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01902225
|United States, California|
|University of California, San Francisco|
|San Francisco, California, United States, 94115|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Ai Wei, M.D.||University of California, San Francisco|