A Phase 2 Multicenter Study of High Dose Chemotherapy With Autologous Stem Cell Transplant Followed by Maintenance Therapy With Romidepsin for the Treatment of T Cell Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to test the benefit of a chemotherapy drug called romidepsin in patients with T Cell Non-Hodgkin Lymphoma (T NHL) who have undergone autologous transplantation.

Detailed Description
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The primary aim is to determine a preliminary estimate of the progression-free survival of patients with T NHL who receive maintenance romidepsin at 2 years post-transplant for patients transplanted in CR1 or PR1 with standard risk histologies. Secondary aims include: Determine PFS at 2 yrs for patients transplanted in ≥CR/PR2 or for patients with high risk histologies. Determine the toxicities associated with romidepsin following autologous transplantation Determine the probability of OS at 2 years post transplant for all patients undergoing transplant Characterize the effect of romidepsin on immune recovery post HDT-ASCT OS and PFS 1 year after Romidespin completion Patients who receive romidepsin after transplant will be evaluable for the primary endpoint, and will be counted towards the accrual total. Any patient who does not receive romidepsin after transplant, regardless of reason, will be replaced. We will also accrue a second cohort of 8 patients who are transplanted in >CR/PR2 and for high risk histologies to be analyzed for secondary endpoints only. This cohort will not be part of the primary endpoint and will be analyzed for summary statistics only. Patients who receive romidepsin after transplant will be counted towards the accrual total for Cohort 2. Any patient who does not receive romidepsin after transplant, regardless of reason, will be replaced.

Official Title
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A Phase 2 Multicenter Study of High Dose Chemotherapy With Autologous Stem Cell Transplant Followed by Maintenance Therapy With Romidepsin for the Treatment of T Cell Non-Hodgkin Lymphoma

Conditions
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T Cell Non-Hodgkin Lymphoma

Intervention / Treatment
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* Other: High Dose Chemotherapy with Autologous Stem Cell Transplant Followed by Maintenance Therapy with Romidepsin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: Patients over age 16 who are deemed eligible for transplant by their treating physician Disease status: CR or PR required. Remission status will be assessed at the completion of induction chemotherapy and prior to enrollment on protocol. Diagnosis: The following histologies will need to be confirmed at MSK or locally for participating sites in order to be considered for HDT-ASCT and post-transplant maintenance romidepsin: PTCL AITL ALCL EaTCL Hepatosplenic Gamma Delta T cell lymphoma Adult T-cell leukemia/lymphoma Primary cutaneous gamma/delta T-cell lymphoma Extranodal NK/T-cell lymphoma, nasal type Primary cutaneous anaplastic large cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Mycosis fungoides/sezary syndrome Stem cell collection: A minimum of 2 x 106 CD34+ cells must have been collected Laboratory test results within these ranges: Total bilirubin <= 1.5 x ULN AST (SGOT) and ALT (SGPT) <= 3 x ULN Exclusion Criteria: Diagnosis: progressive disease at transplant work-up Prior therapy: prior autologous or allogeneic transplant Active and uncontrolled infection at time of transplantation including active infection with Aspergillus or other mold, or HIV infection Inadequate performance status/organ function defined by DLCO < 50% (adjusted for hgb), cardiac function as defined below, KPS < 60%. Pregnant or breast feeding. For males and females of child-producing potential, inability to use effective contraceptive methods during the study Prior therapy with romidepsin Central nervous system or meningeal involvement Any known cardiac abnormalities such as: Congenital long QT syndrome QTc interval ≥ 500 milliseconds Myocardial infarction within 6 months of transplantation. Subjects with a history of myocardial infarction between 6 and 12 months prior to transplant 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 (see Appendix 1) 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 2) and/or ejection fraction <40% by 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, defined as blood pressure (BP) of ≥160/95; patients who have 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) Patients taking drugs leading to significant QT prolongation within the specified wash out period (See Appendix 3: Medications That May Cause QTc Prolongation). Concomitant use of CYP3A4 inhibitors

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: high dose chemo w/asct + maintenance txt<br>High dose chemotherapy (Carmustine), VP-16 (etoposide, Vepesid®), Cytarabine (Ara-C), Melphalan (Alkeran)with autologous stem cell transplant followed by maintenance therapy with Romidepsin (Istodax) | Other: High Dose Chemotherapy with Autologous Stem Cell Transplant Followed by Maintenance Therapy with Romidepsin<br> <br> * Other names: Romidepsin (Istodax);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The progression-free survival of patients | The progression-free survival of patients with T NHL who receive maintenance romidepsin at 2 years post-transplant for patients transplanted in CR1 or PR1 with standard risk histologies. | 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival for patients with high risk histologies | Determine PFS at 2 yrs for patients transplanted in ≥CR/PR2 or for patients with high risk histologies. | 2 Years | 
| Toxicities | Determine the toxicities associated with romidepsin following autologous transplantation. Toxicities will be graded on a scale of 0 to 5 as described by the NCI- Common Terminology for Adverse Events (CTCAE), version 4.0 | 2 years | 
| Probability of OS at 2 years post transplant | Determine the probability of OS at 2 years post transplant for all patients undergoing transplant | 2 year post transplant | 
| OS 1 year after Romidespin completion | OS 1 year after Romidespin completion | 1 year | 
| PFS 1 year after Romidespin completion | PFS 1 year after Romidespin completion | 1 year |