LymphomaPhase 1NCT01902225
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
A Phase 1 study testing Istodax and Doxil in people with Lymphoma and T-Cell Lymphoma, run by Weiyun Ai at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, T-Cell Lymphoma, Cutaneous Lymphoma
- What is being tested?
- Istodax and Doxil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- 4 Mar 2014to 11 Apr 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Life expectancy >90 days.
Who cannot join
- 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.
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- 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
- An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of ≥2 mm, measured from isoelectric line to the ST segment). If in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
- Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions (see Appendix 10) and/or ejection fraction <40% by Multigated Acquisition Scan (MUGA) scan or <50% by echocardiogram and/or MRI
- A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)
- Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes
- Uncontrolled hypertension, i.e., blood pressure (BP) of ≥160/95; patients with a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria
- Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
- Any cardiac finding that is deemed ineligible at the discretion of the investigator
- Patients taking drugs leading to significant QT prolongation and unable to stop drugs prior to treatment
- Concomitant use of CYP3A4 inhibitors or inducers unless able to stop medication(s) prior to starting study therapies
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
University of California, San Francisco
San Francisco, California, 94115
About this study
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
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.
Read the detailed description
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.
STUDY ENDPOINTS:
Primary:
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.
Secondary:
- 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.
Exploratory:
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.
- Conditions
- Lymphoma, T-Cell Lymphoma, Cutaneous Lymphoma
- Being tested
- Istodax, Doxil
- Keywords
- Lymphoma, T-Cell, Cutaneous, Doxil, romidepsin, skin
- Medical subject headings
- Lymphoma, Lymphoma, T-Cell, Lymphoma, T-Cell, Cutaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IstodaxDrug
Also called Romidepsin
DoxilDrug
Also called Liposomal doxorubicin
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Istodax; Drug: Doxil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Up to 2 years
Secondary outcomes (8)
Complete response (CR) rate
Measured: Up to 2 years
Overall response rate (CR + PR)
Measured: Up to 2 years
Time to response (TTR)
Measured: Up to 2 years
Duration of response (DOR)
Measured: Up to 2 years
Time to progression (TTP)
Measured: Up to 2 years
Changes in degree of pruritus
Measured: Up to 2 years
Quality of life during therapy
Measured: Up to 2 years
Changes in skin related symptoms
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2013 (estimated)
- Study start4 Mar 2014
- Primary completion13 Jul 2018
- Study completion11 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weiyun Ai
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation
- Responsible party
- Sponsor-investigator, Weiyun Ai, University of California, San Francisco
- Investigators
- Ai Wei, M.D., Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01902225
- Sponsor's protocol ID
- 112516
- Other IDs
- NCI-2014-01722
- Status last verified
- Jun 2020
- First submitted
- 15 Jul 2013
- Last updated
- 9 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01902225
- Acronym / sponsor ID
- 112516
- Conditions
- Lymphoma, T-Cell Lymphoma, Cutaneous Lymphoma
- Keywords
- Lymphoma, T-Cell, Cutaneous, Doxil, romidepsin, skin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Weiyun AiUniversity, hospital or other
- Collaborators
- Celgene Corporation
- Study start
- 4 Mar 2014 (actual)
- Primary completion
- 13 Jul 2018 (actual)
- Study completion
- 11 Apr 2020 (actual)
- First posted
- 18 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
STUDY ENDPOINTS:
Primary:
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.
Secondary:
- 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.
Exploratory:
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Istodax, Doxil | Experimental | Drug: Istodax, Drug: DoxilIstodax; Intravenous; 8-14 mg/m2; Days 1, 8, and 15; over 4 hours Doxil; Intravenous; 20 mg/m2; Day 1; over 1 hour |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IstodaxAlso: Romidepsin | Drug | Istodax, Doxil |
| DoxilAlso: Liposomal doxorubicin | Drug | Istodax, Doxil |
Primary outcome
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)
8 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ai Wei, M.D. principal investigator
University of California, San Francisco
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Istodax and Doxil in people with Lymphoma and T-Cell Lymphoma, run by Weiyun Ai at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2020.