Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Romidepsin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Among patients with relapsed or refractory peripheral T-Cell lymphoma, patients who received Istodax will be targeted in this surveillance

Istodax

Jinshu Cho, MD

To ascertain the safety and efficacy of Istodax® in actual clinical settings in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) who receive Istodax.

1. Planned registration period 4 years
2. Planned surveillance period 5 years and 6 months

ISTODAX® for Intravenous Infusion Drug Use Results Survey- Relapsed or Refractory Peripheral T-Cell Lymphoma

ISTODAX® for Intravenous Infusion 10mg Drug Use Results Survey - Relapsed or Refractory Peripheral T-Cell Lymphoma

Number of participants with adverse event

Celgene

Hematologic Neoplasms

Hematologic Diseases

Rifampin

Antitubercular Agents

Romidepsin 14 mg/m\^2 intravenous infused over 4 hours on Day 1 and Day 8.

Rifampin 600 mg oral once daily on Days 4-8

14 mg/m\^2 intravenous infused over 4 hours on Day 1 and Day 8.

Ken Takeshita, MD

The purpose of this study is to evaluate the effect and safety of multiple doses of rifampin on the pharmacokinetics of romidepsin after a single intravenous (IV) infusion.

Influence of Rifampin on the Pharmacokinetics of Romidepsin in Patients With Advanced Cancer

A Phase I Open-label, 2-period Study to Evaluate the Influence of Multiple Oral Doses of Rifampin on the Single Dose Pharmacokinetics of Romidepsin in Subjects With Advanced Cancer

AUC0-t: area under the plasma concentration time-curve from Time 0 to the time of the last quantifiable concentration (Ct), calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.

Individual and mean romidepsin plasma concentrations by treatment and scheduled time data were collected. AUC0-24: area under the plasma concentration time-curve from Time 0 to 24 hours, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.

AUC0-∞: area under the plasma concentration time-curve from Time 0 extrapolated to infinity, calculated as \[AUCt + Ct/λz\]. λz is the apparent terminal rate constant. No AUC extrapolation was performed with unreliable λz. If the percentage of AUC extrapolated is ≥ 25%, AUC0-∞ will not be reported.

Maximum observed plasma concentration (Cmax)was obtained directly from the observed concentration versus time data.

Time to maximum observed plasma concentration (Tmax) was obtained directly from the observed concentration versus time data.

The terminal elimination half-life (t1/2) in plasma, was calculated as \[(ln 2)/λz\]. This was only calculated when a reliable estimate for λz could be obtained.

The apparent total plasma clearance (CL) was calculated as \[Dose/AUC0-∞\] for Romidepsin alone and co-administered with rifampin plasma concentrations.

Apparent total volume of distribution (Vz) was calculated as \[(CL)/λz\] for Romidepsin and co-administered with Rifampin.

AEs were considered related if assessed by the Investigator as possibly, probably or definitely related to study drug. Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above.

Romidepsin 14 mg/m\^2 intravenous infused over 4 hours on Day 1 and Day 8 and Rifampin 600 mg oral once daily on Days 4-8.

Romidepsin Plus Rifampin

Romidepsin and Rifampin

Age, Continuous

Sex: Female, Male

White

Black or African American

Other

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Unknown or Not Reported

United Kingdom

United States

Region of Enrollment

Height

Weight

Body Surface Area (BSA)

0 = Fully active

1 = Restricted in physical strenuous activity

2 = Ambulaotry but unable to work

3 = Limited Self-Care

4 = Completely Disabled

Eastern Cooperative Oncology Group (ECOG) Performance Status is used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease affects the daily living activities of the patient and determine appropriate treatment and prognosis.

0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity)

Eastern Cooperative Oncology Group Performance Status (ECOG)

Senior Manager, Clinical Trials Disclosure

Romidepsin 14 mg/m\^2 intravenous infused over 4 hours on Day 1 and Day 8.

Romidepsin Day 1

Romidepsin 14mg/m\^2 intravenous infused over 4 hours on Day 8. Rifampin 600mg oral once daily on Days 4-8.

Romidepsin and Rifampin Day 8

The PK population included all participants who received at least 1 dose of study drug and had evaluable PK profiles. The primary reason for study discontinuation for the 1 participant was due to withdrawal of consent.

Area Under the Plasma Concentration Time-curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t)of Romidepsin

Romidepsin 14 mg/m\^2 intravenous infused over 4 hours on Day 1.

Rifampin 600 mg oral once daily on Days 4-8

Romidepsin 14 mg/m\^2 intravenous infused over 4 hours on Day 8. Rifampin 600 mg oral once daily on Days 4-8

Area Under the Plasma Concentration Time-curve From Time 0 to 24-hour (AUC0-24) for Romidepsin

Romidepsin 14 mg/m\^2 intravenous infused over 4 hours on Day 1

Romidepsin 14 mg/m\^2 intravenous infused over 4 hours on Day 8. Rifampin 600 mg oral once daily on Days 4-8.

The primary objective was to assess the influence of multiple doses of rifampin on the PK of romidepsin. The PK population included all participants who received at least 1 dose of study drug and had evaluable PK profiles. The primary reason for study discontinuation for the 1 participant was due to withdrawal of consent.

Area Under the Plasma Concentration Time-curve From Time Zero Extrapolated to Infinity (AUC0-∞).

Romidepsin 14 mg/m\^2 intravenous infused over 4 hours on Day 1.

Romidepsin 14 mg/m\^2 intravenous infused over 4 hours on Day 8. Rifampin 600mg oral once daily on Days 4-8

Maximum Observed Plasma Concentration (Cmax)of Romidepsin

Note: The median, median difference ("romidepsin + rifampin" minus "romidepsin") and 90% CI of the median difference are from Hodges-Lehmann Estimate. The P-value is from Wilcoxon signed-rank test.

Time to Maximum Observed Plasma Concentration (Tmax)

Estimate of the Terminal Elimination Half-life in Plasma (t1/2)

Clearance (CL): Apparent Total Plasma Clearance.

The PK population was to consist of all participants who received at least 1 dose of study drug and had evaluable PK profiles.

Apparent Total Volume of Distribution (Vz).

= > 1 TEAE

= > 1 TEAE related to any study drug

= > 1 TEAE related to Romidepsin

= > 1 TEAE related to Rifampin

= > 1 Serious TEAE

= > 1 Serious TEAE related to any drug

= > 1 Serious TEAE related to Romidepsin

= > 1 Serious TEAE related to Rifampin

= > 1 TEAE leading to discontinuation

= > 1 TEAE related discontinuation to any drug

= > 1 Romidepsin related TEAE discontinuation

= > 1 Rifampin related TEAE discontinuation

Participants who died

Romidepsin 14 mg/m\^2 intravenous infused over 4 hours on Days 1 and 8. Rifampin 600 mg oral once daily on Days 4-8

The safety population included all subjects who received at least 1 dose of study drug.

Summary of Participants With Treatment Emergent Adverse Events (TEAEs)

Overall Study

Ketoconazole

Clotrimazole

Miconazole

Antifungal Agents

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Romidepsin 8 mg/m\^2 intravenous infused over 4 hours on Day 1 and Day 8.

Ketoconazole 400 mg oral once daily on Days 4-8

Romidepsin 8 mg/m\^2 intravenous infused over 4 hours on Day 1 and Day 8.

Ketoconazole 400 mg oral once daily on Days 4-8

The purpose of this study is to evaluate the effect and safety of multiple doses of ketoconazole on the pharmacokinetics of romidepsin after a single intravenous (IV) infusion.

Influence of Ketoconazole on the Pharmacokinetics of Romidepsin in Patients With Advanced Cancer

A Phase I Open-label, 2-period Study to Evaluate the Influence of Multiple Oral Doses of Ketoconazole on the Single Dose Pharmacokinetics of Romidepsin in Subjects With Advanced Cancer

AUC0-t: area under the plasma concentration time-curve from Time 0 to the time of the last quantifiable concentration (Ct), calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing. For AUC0-t, an analysis of variance (ANOVA) model was used to estimate the ratio of geometric means and its 90% CI between romidepsin alone and romidepsin in the presence to ketoconazole.

AUC 0-24: area under the plasma concentration time-curve from Time 0 to 24 hours, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing; for AUC 0-24 an analysis of variance (ANOVA) model was used to estimate the ratio of geometric means and its 90% confidence interval (CI) between romidepsin alone and romidepsin in the presence of ketoconazole

AUC0-∞: area under the plasma concentration time-curve from Time 0 extrapolated to infinity, calculated as \[AUCt + Ct/λz\].

Cmax: maximum observed plasma concentration, obtained directly from the observed concentration versus time data; for Cmax, an analysis of variance (ANOVA) model was used to estimate the ratio of geometric means and its 90% confidence interval (CI) between romidepsin alone and romidepsin in the presence of ketoconazole

Tmax: time to maximum observed Tmax, obtained directly from the observed concentration versus time data

Terminal elimination half-life (t1/2) in plasma, was calculated as \[(ln 2)/λz\]

Apparent total plasma clearance, (CL) calculated as \[Dose/AUC 0-∞\].

Vz: apparent total volume of distribution, calculated as \[(CL)/λz\].

All 15 subjects in the safety population received at least 1 dose of romidepsin. AEs were considered related if assessed by the Investigator as possibly, probably or definitely related to study drug. Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above.

Romidepsin 8 mg/m\^2 intravenous infused over 4 hours on Day 1 and Day 8. Ketoconazole 400 mg oral once daily on Days 4-8

Romidepsin Plus Ketoconazole

Romidepsin and Ketoconazole

Ethnicity (NIH/OMB)

Asian

0 = Fully Active

2 = Ambulatory but unable to work

3 = Limited Self Care

Eastern Cooperative Oncology Group (ECOG) Performance Status is used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease affects the daily living activities of the patient and determine appropriate treatment and prognosis.

0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care

Senior Manager

Romidepsin 8 mg/m\^2 intravenous infused over 4 hours on Day 1

Romidepsin 8 mg/m\^2 intravenous infused over 4 hours on Day 8; Ketoconazole 400 mg oral once daily on Days 4-8

Romidepsin and Ketoconazole Day 8

Assessment on the influence of multiple doses of ketoconazole on the Pharmacokinetic (PK) of romidepsin; the PK population included participants who received at least 1 dose of study drug and had evaluable PK profiles. The reasons for study discontinuation: 1 subject withdrew due to an AE while another subject had disease progression.

Assess the influence of multiple doses of ketoconazole on the pharmacokinetic (PK) of romidepsin; the PK population included participants who received at least 1 dose of study drug and had evaluable PK profiles. The reasons for study discontinuation: 1 subject withdrew due to an AE while another subject had disease progression.

Area Under the Plasma Concentration Time-curve From Time 0 to 24-hour (AUC 0-24)

Assess the influence of multiple doses of ketoconazole on the PK of romidepsin. The PK population included participants who received at least 1 dose of study drug and had evaluable PK profiles. The reasons for study discontinuation: 1 subject withdrew due to an AE while another subject had disease progression.

Area Under the Plasma Concentration Time-curve From Time 0 Extrapolated to Infinity (AUC0-∞)

Maximum Observed Plasma Concentration (Cmax)

Note: The median, median difference ("romidepsin + ketoconazole" minus "romidepsin") and 90% CI of the median difference are from Hodges-Lehmann Estimate. The P-value is from Wilcoxon signed-rank test.

Assess the influence of multiple doses of ketoconazole on the PK of romidepsin; the PK population included participants who received at least 1 dose of study drug and had evaluable PK profiles. The reasons for study discontinuation: 1 subject withdrew due to an AE while another subject had disease progression.

Apparent Total Plasma Clearance (CL)

Apparent Total Volume of Distribution (Vz)

= > 1 TEAE related to Ketoconazole

= > 1 Serious TEAE related to Ketoconazole

= > 1 TEAE related discontinuation due to any drug

= > 1 Ketoconazole related TEAE discontinuation

Romidepsin 8 mg/m2 intravenous infused over 4 hours on Day 1 and Day 8. Ketoconazole 400 mg oral once daily on Days 4-8

The safety population consisted of all participants who received at least 1 dose of study drug. The Day 8 analysis population included 13 participants because two participants discontinued from the study prior to Day 8 (one due to an AE, the other due to disease progression).

Romidepsin 8 mg/m\^2 intravenous infused over 4 hours on Day 1 and Day 8

Ketoconazole 400 mg oral once daily on Days 4-8

Lymphoma, T-Cell, Cutaneous

Cutaneous T-cell Lymphoma

Doxorubicin

Liposomal doxorubicin

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

Doxil; Intravenous; 20 mg/m2; Day 1; over 1 hour

Doxil

Ai Wei, M.D.

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.

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.

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 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

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)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
ISTODAX® for Intravenous Infusion Drug Use Results Survey- Relapsed or Refractory Peripheral T-Cell Lymphoma	NCT03742921	Lymphoma, T-Cel...	Istodax	-	Celgene
Influence of Rifampin on the Pharmacokinetics of Romidepsin in Patients With Advanced Cancer	NCT01324323	Hematologic Mal... Malignant Lymph...	Romidepsin Rifampin	18 Years -	Celgene
Influence of Ketoconazole on the Pharmacokinetics of Romidepsin in Patients With Advanced Cancer	NCT01324310	Hematologic Mal... Malignant Lymph...	Romidepsin Ketoconazole	18 Years -	Celgene
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	Lymphoma T-Cell Lymphoma Cutaneous Lymph...	Istodax Doxil	18 Years -	University of California, San Francisco
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	Lymphoma T-Cell Lymphoma Cutaneous Lymph...	Istodax Doxil	18 Years -	University of California, San Francisco

Spots Global Cancer Trial Database for istodax

Every month we try and update this database with for istodax cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for istodax

Every month we try and update this database with for istodax cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for istodax cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.