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

This study is currently recruiting participants.
Verified April 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
University of Washington
Weill Medical College of Cornell University
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01908777
First received: July 17, 2013
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
T Cell Non-Hodgkin Lymphoma
Other: High Dose Chemotherapy with Autologous Stem Cell Transplant Followed by Maintenance Therapy with Romidepsin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • The progression-free survival of patients [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Progression Free Survival for patients with high risk histologies [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    Determine PFS at 2 yrs for patients transplanted in ≥CR/PR2 or for patients with high risk histologies.

  • Toxicities [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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

  • Probability of OS at 2 years post transplant [ Time Frame: 2 year post transplant ] [ Designated as safety issue: No ]
    Determine the probability of OS at 2 years post transplant for all patients undergoing transplant

  • OS 1 year after Romidespin completion [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    OS 1 year after Romidespin completion

  • PFS 1 year after Romidespin completion [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    PFS 1 year after Romidespin completion


Estimated Enrollment: 33
Study Start Date: July 2013
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: high dose chemo w/asct + maintenance txt
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
Other Names:
  • Carmustine
  • VP-16 (etoposide, Vepesid®)
  • Cytarabine (Ara-C)
  • Melphalan (Alkeran)
  • Romidepsin (Istodax)

Detailed Description:

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
  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 MSKCC 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01908777

Contacts
Contact: Jenna Goldberg, MD 212-639-4828
Contact: Steven Horowitz, MD 212-639-3045

Locations
United States, New Jersey
Memoral Sloan Kettering Cancer Center Recruiting
Basking Ridge, New Jersey, United States
Contact: Jenna Goldberg, MD    212-639-4828      
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Jenna Goldberg, MD    212-639-4828      
Weill Cornell Medical Center Recruiting
New York, New York, United States
Contact: Jia Ruan, MD         
Principal Investigator: Jia Ruan, MD         
Memorial Sloan-Kettering Cancer Center Recruiting
NY, New York, United States, 11065
Contact: Jenna Goldberg, MD    212-639-4828      
Contact: Steven Horwitz, MD    212-639-3045      
Principal Investigator: Jenna Goldberg, MD         
Memorial Sloan-Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Jenna Goldberg, MD    212-639-4828      
Memoral Sloan Kettering Cancer Center at Phelps Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Jenna Goldberg, MD    212-639-4828      
United States, Washington
University of Washington School of Medicine Not yet recruiting
Seattle, Washington, United States, 98109
Contact: Andrei Shustov, MD         
Principal Investigator: Andrei Shustov, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
University of Washington
Weill Medical College of Cornell University
Investigators
Principal Investigator: Jenna Goldberg, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01908777     History of Changes
Other Study ID Numbers: 13-020
Study First Received: July 17, 2013
Last Updated: April 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Carmustine
Melphalan
Romidepsin
Cytarabine
Etoposide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Myeloablative Agonists
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on April 15, 2014