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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01908777
Recruitment Status : Active, not recruiting
First Posted : July 26, 2013
Last Update Posted : February 27, 2020
Sponsor:
Collaborators:
University of Washington
Weill Medical College of Cornell University
H. Lee Moffitt Cancer Center and Research Institute
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE July 17, 2013
First Posted Date  ICMJE July 26, 2013
Last Update Posted Date February 27, 2020
Study Start Date  ICMJE July 16, 2013
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 23, 2013)
The progression-free survival of patients [ Time Frame: 2 Years ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2013)
  • Progression Free Survival for patients with high risk histologies [ Time Frame: 2 Years ]
    Determine PFS at 2 yrs for patients transplanted in ≥CR/PR2 or for patients with high risk histologies.
  • Toxicities [ Time Frame: 2 years ]
    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 ]
    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 ]
    OS 1 year after Romidespin completion
  • PFS 1 year after Romidespin completion [ Time Frame: 1 year ]
    PFS 1 year after Romidespin completion
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary 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

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE T Cell Non-Hodgkin Lymphoma
Intervention  ICMJE 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)
Study Arms  ICMJE 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)
Intervention: Other: High Dose Chemotherapy with Autologous Stem Cell Transplant Followed by Maintenance Therapy with Romidepsin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 26, 2020)
47
Original Estimated Enrollment  ICMJE
 (submitted: July 23, 2013)
33
Estimated Study Completion Date  ICMJE July 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01908777
Other Study ID Numbers  ICMJE 13-020
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE
  • University of Washington
  • Weill Medical College of Cornell University
  • H. Lee Moffitt Cancer Center and Research Institute
Investigators  ICMJE
Principal Investigator: Steven Horowitz, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP