Belinostat Combined With Azacitidine/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Refractory or Relapsed Lymphoma
Lymphoma
About this trial
This is an interventional treatment trial for Lymphoma focused on measuring Refractory or Relapsed Lymphoma, Busulfan, Busulfex, Myleran, Caphosol, Glutamine, Enterex, Glutapak-10, NutreStore, Resource, GlutaSolve, Sympt-X-G.I., Sympt-X, Pyridoxine, Belinostat, Azacitidine, 5-azacytidine, 5-aza, Azacytidine, Vidaza, 5-AZC, AZA-CR, Ladakamycin, Gemcitabine, Gemcitabine Hydrochloride, Gemzar, Stem cell transplant, SCT, Melphalan, Alkeran
Eligibility Criteria
Inclusion Criteria:
- Age 15-65
- Patients with: 2. 1. DLBCL with one of the following: 2.1.1. Primary refractory (no CR to 1st line). 2.1.2. High-risk relapse (CR1 <6 months, secondary IPI >1, high LDH). 2.1.3. Refractory relapse: No response (SD or PD) to >/= 1 line of salvage. 2.2. Hodgkin's with one of the following: 2.2.1. Primary refractory (no CR to 1st line or PD within 3 months). 2.2.2. High-risk relapse (CR1 <1 year, extranodal relapse, B symptoms). 2.2.3. Refractory relapse: No response (SD or PD) to >/= 1 line of salvage. 2.3. T-NHL with one of the following: 2.3.1. Primary refractory (</= CR to 1st line or relapse within 6 months). 2.3.2. Nonresponsive (SD/PD) to >/= 1 line of salvage. 2.4. Burkitt's or lymphoblastic lymphoma with one of the following: 2.4.1. Primary refractory (</= CR to 1st line or relapse within 6 months). 2.4.2. Refractory to at least 1 line of salvage (SD/PD).
- Adequate renal function, as defined by estimated serum creatinine clearance >/= 50 ml/min and/or serum creatinine </= 1.8 mg/dL.
- Adequate hepatic function (SGOT and/or serum glutamate pyruvate transaminase (SGPT) </= 3 x upper limit of normal (ULN); bilirubin and ALP </= 2 x ULN.
- Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) (corrected for Hgb) >/= 50%.
- Adequate cardiac function with left ventricular ejection fraction >/= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
- PS <2.
- Negative Beta human chorionic gonadotropin (HCG) in woman with child-bearing potential.
Exclusion Criteria:
- Grade >/= 3 non-hematologic toxicity from previous therapy that has not resolved to </= G1.
- Prior whole brain irradiation.
- Corrected QT interval (QTc) longer than 500 ms.
- Active hepatitis B, either active carrier (HBsAg +) or viremic (HBV 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.
- Active infection requiring parenteral antibiotics.
- HIV infection, unless receiving effective antiretroviral therapy with undetectable viral load and normal cluster of differentiation 4 (CD4) counts.
- Radiation therapy in the month prior to enrollment.
Sites / Locations
Arms of the Study
Arm 1
Experimental
Belinostat/Gem/Bu/Mel + AutoSCT
Busulfan "test dose" administered by vein on Day -10. Test dose of 32 mg/m2 based on actual body weight. Busulfan pharmacokinetics performed with the test dose and the first dose on Day -8. Doses on Days -6 and -5 subsequently adjusted to target an area under curve (AUC) of 4,000 microMol.min-1. Caphosol oral rinses 30 mL four times a day used from Day -8. Oral Glutamine, 15 g swished, gargled and swallowed four times a day starting on Day -8. Pyridoxine 100 mg by vein or mouth three times a day staring on Day -1. Starting dose of Belinostat 100 mg/ m2/day by vein on Day -9 through Day -2. Azacitidine 15 mg/m2/day by vein on Day -9 through Day -2. Participants with cluster of differentiation antigen 20 (CD20+) tumors receive Rituximab 375 mg/m2 by vein on Day -9. Gemcitabine 75 mg/m2 by vein administered as a loading dose followed by prolonged infusion on Days -8 and -3. Melphalan 60 mg/m2/d by vein on Day -2. Stem cell transplant by vein given on Day 0.