Chemotherapy, Stem Cell Transplant, and Romidepsin in Treating Patients with T-cell Non-Hodgkin Lymphoma

Status: Active

Description

This phase II trial studies how well chemotherapy, stem cell transplant, and romidepsin work in treating patients with T-cell non-Hodgkin lymphoma. Giving chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. The patient’s stem cells that were previously collected are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Drugs used in chemotherapy, such as romidepsin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving romidepsin following stem cell transplant may be an effective treatment for T-cell non-Hodgkin lymphoma.

Eligibility Criteria

Inclusion Criteria

  • CR or PR required; remission status will be assessed at the completion of induction chemotherapy and prior to enrollment on protocol
  • The following histologies will need to be confirmed at Memorial Sloan-Kettering Cancer Center (MSK) or locally for participating sites in order to be considered for HDT-ASCT and post-transplant maintenance romidepsin: * Peripheral T-cell lymphoma (PTCL) * Angioimmunoblastic T-cell lymphoma (AITL) * Anaplastic large-cell lymphoma (ALCL) * Enteropathy-associated T-cell lymphoma (EaTCL) * Hepatosplenic gamma delta T-cell lymphoma * Adult T-cell leukemia/lymphoma * Primary cutaneous gamma/delta T-cell lymphoma * Extranodal natural killer (NK)/T-cell lymphoma, nasal type * Primary cutaneous anaplastic large cell lymphoma * Subcutaneous panniculitis-like T-cell lymphoma * Mycosis fungoides/Sezary syndrome
  • A minimum of 2 x 10^6 cluster of differentiation 34 positive (CD34+) cells must have been collected
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN

Exclusion Criteria

  • Progressive disease at transplant work-up
  • Prior autologous or allogeneic transplant
  • Active and uncontrolled infection at time of transplantation including active infection with Aspergillus or other mold, or human immunodeficiency virus (HIV) infection
  • Inadequate performance status/organ function defined by diffusing capacity of the lung for carbon monoxide (DLCO) < 50% (adjusted for hemoglobin [hgb]), cardiac function as defined below, Karnofsky performance status (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 * Corrected QT (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 electrocardiogram (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 and/or ejection fraction < 40% by multi gated acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI) * A known history or 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) >= 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 * Concomitant use of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors
  • Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up and research tests

Locations & Contacts

Florida

Tampa
Moffitt Cancer Center
Status: Active
Contact: Farhad Khimani
Phone: 888-663-3488

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Steven Michael Horwitz
Phone: 212-639-3045
Email: horwitzs@mskcc.org
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Steven Michael Horwitz
Phone: 212-639-3045
Email: horwitzs@mskcc.org

New York

Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Steven Michael Horwitz
Phone: 212-639-3045
Email: horwitzs@mskcc.org
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Steven Michael Horwitz
Phone: 212-639-3045
Email: horwitzs@mskcc.org
NYP / Weill Cornell Medical Center
Status: Active
Contact: Jia Ruan
Phone: 646-962-2064
Email: jruan@med.cornell.edu
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Steven Michael Horwitz
Phone: 212-639-3045
Email: horwitzs@mskcc.org
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Steven Michael Horwitz
Phone: 212-639-3045
Email: horwitzs@mskcc.org

Washington

Seattle
Fred Hutchinson Cancer Research Center
Status: Active
Contact: Andrei R. Shustov
Phone: 855-557-0555
Email: ashustov@u.washington.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine a preliminary estimate of the progression-free survival of patients with T non-Hodgkin lymphoma (NHL) who receive maintenance romidepsin at 2 years post-transplant for patients transplanted in first complete remission (CR1) or first partial remission (PR1) with standard risk histologies.

SECONDARY OBJECTIVES:

I. Determine progression-free survival (PFS) at 2 years for patients transplanted in >= complete remission (CR)/second partial remission (PR2) or for patients with high risk histologies.

II. Determine the toxicities associated with romidepsin following autologous transplantation.

III. Determine the probability of overall survival (OS) at 2 years post-transplant for all patients undergoing transplant.

IV. Characterize the effect of romidepsin on immune recovery post high dose chemotherapy with autologous stem cell transplant (HDT-ASCT).

V. OS and PFS 1 year after romidepsin completion.

OUTLINE:

BEAM CHEMOTHERAPY: Patients receive carmustine intravenously (IV) over 2 hours on day -6, etoposide IV over 1 hour every 12 hours on days -5 to -2, cytarabine IV every 12 hours on days -5 to -2, and melphalan IV on day -1.

TRANSPLANT: Patients undergo autologous stem cell transplant on day 0.

MAINTENANCE: Beginning 42-80 days after transplant, patients receive romidepsin IV once every other week for 6 months, once every 3 weeks between 6 months and 1 year, and every 4 weeks between 1 and 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 year.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Steven Michael Horwitz

Trial IDs

Primary ID 13-020
Secondary IDs NCI-2013-01365
Clinicaltrials.gov ID NCT01908777