Chemotherapy, Stem Cell Transplant, and Romidepsin in Treating Patients with T-cell Non-Hodgkin Lymphoma
- 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
- 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
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.
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.
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 Phase II
Trial Type Treatment
Memorial Sloan Kettering Cancer Center
Steven Michael Horwitz
- Primary ID 13-020
- Secondary IDs NCI-2013-01365
- Clinicaltrials.gov ID NCT01908777