Romidepsin in Conditioning and Maintenance in Patients with T-cell Leukemia or Lymphoma Undergoing Donor Stem Cell Transplant
Inclusion Criteria
- Diagnosis of either cutaneous T-cell lymphoma; T-prolymphocytic leukemia; T-large granulocytic leukemia; T-lymphoblastic leukemia/lymphoma; or peripheral T-cell lymphoma, natural killer/T-cell lymphoma for whom allogeneic stem cell transplantation is indicated
- An 10/10 or 8/8 human leukocyte antigen (HLA) matched (high resolution typing at A, B, C, DRB1, DQ1) sibling or unrelated donor
- Ejection fraction (EF) >= 50% on multi gated acquisition (MUGA) scan or echocardiogram
- Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and corrected diffusing capacity of the lungs for carbon monoxide (DLCO) >= 40%
- Estimated serum creatinine clearance >= 50 ml/min (using the Cockcroft-Gault formula) and/or serum creatinine =< 1.6 mg/dL; renal function will be calculated using ideal body weight (IBW), unless a patient weighs > 40% of their IBW, then adjusted body weight will be utilized
- Serum bilirubin =< 1.5 x upper limit of normal
- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 2 x upper limit of normal
- Able to sign informed consent
- Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study; female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study; male subject agrees to use an acceptable method for contraception for the duration of the study
Exclusion Criteria
- Patient with active central nervous system (CNS) disease
- Pregnancy (positive beta human chorionic gonadotropin [HCG] test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization) or currently breast-feeding; pregnancy testing is not required for post-menopausal or surgically sterilized women
- Active hepatitis B, either active carrier (hepatitis B surface antigen positive [HBsAg +]) or viremic (hepatitis B virus [HBV] deoxyribonucleic acid [DNA] >=10,000 copies/mL, or >= 2,000 IU/mL)
- Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology
- Human immunodeficiency virus (HIV) infection
- Active uncontrolled bacterial, viral or fungal infections
- Exposure to other investigational drugs within 4 weeks before enrollment
- Grade >= 3 non-hematologic toxicity from previous therapy that has not resolved to =< grade 1
- Radiation therapy to head and neck (excluding eyes), and internal organs of chest, abdomen or pelvis in the month prior to enrollment
- Prior whole brain irradiation
- Prior autologous stem cell transplant (SCT) in the prior 12 months
- Congenital QT syndrome, corrected QT (QTc) > 500 ms
- Myocardial infarction within 1 year of study entry; subjects with a history of myocardial infarction between 6 and 12 months prior to study entry 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 (EKG) abnormalities including second (2nd) degree atrio-ventricular (AV) block type II, third (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 EKG 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 MUGA scan or < 50% by echocardiogram and/or magnetic resonance imaging (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, i.e., blood pressure (BP) of >= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose and meet all other inclusion criteria; or
- Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
- Patients taking drugs leading to significant QT prolongation where the interaction is too great to proceed with romidepsin
- Concomitant use of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors where the interaction is thought too great to proceed with romidepsin
Ohio
Columbus
Texas
Houston
PRIMARY OBJECTIVES:
I. To determine the most safe and efficacious dose of romidepsin in conditioning therapy, when combined with busulfan and fludarabine phosphate (fludarabine) for allogeneic stem cell transplantation for T cell leukemia/lymphoma in conjunction with post-transplant maintenance romidepsin.
SECONDARY OBJECTIVES:
I. To determine the safety and feasibility of maintenance romidepsin after allogeneic stem cell transplantation for T cell lymphoma/leukemias.
II. To determine the rates of overall survival (OS) and non-relapse mortality (NRM).
III. To determine the rates of acute graft-versus host disease (aGVHD) and chronic graft-versus-host disease (cGVHD).
IV. To determine the immunologic effects of romidepsin on GVHD, immune recovery, and the graft-versus-tumor effect through correlative studies.
OUTLINE: This is a phase I, dose-escalating study of romidepsin followed by a phase II study.
CONDITIONING: Patients receive busulfan intravenously (IV) over 3 hours on days -13 and -12. Patients also receive romidepsin IV over 4 hours followed by fludarabine phosphate IV over 1 hour and busulfan IV over 3 hours on days -6 to -3. Patients receiving a graft from a matched unrelated donor receive rabbit anti-thymocyte globulin IV over 4 hours on days -3 to -1.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours daily starting on day -2 until patients are able to take it orally (PO) and then PO daily for about 3 months. Patients also receive methotrexate IV over 15 minutes on days 1, 3, 6, and 11.
TRANSPLANT: Patients undergo bone marrow (BM) or peripheral blood stem cell (PBSC) transplant on day 0.
Beginning 28-100 days after transplant, patients receive maintenance romidepsin IV over 1 hour on day 1. Treatment repeats every 14 days for 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 1 year.
Trial Phase Phase I/II
Trial Type Treatment
Lead Organization
Ohio State University Comprehensive Cancer Center
Principal Investigator
Jonathan E. Brammer
- Primary ID OSU-16242
- Secondary IDs NCI-2015-01555, 2017C0008
- Clinicaltrials.gov ID NCT02512497