Panobinostat Combined With High-Dose Gemcitabine/Busulfan/Melphalan With Autologous Stem Cell Transplant for Patients With Refractory/Relapsed Lymphoma
Lymphoma
About this trial
This is an interventional treatment trial for Lymphoma focused on measuring Lymphoma, Refractory/Relapsed Lymphoma, Diffuse large B-cell lymphoma, Hodgkin's lymphoma, T-cell Lymphoma, Palifermin, Kepivance, Panobinostat, LBH589B, Gemcitabine, Gemcitabine Hydrochloride, Gemzar, Busulfan, Busulfex, Myleran, Melphalan, Alkeran, Rituximab, Rituxan, Dexamethasone, Decadron, Caphosol, Glutamine, Enterex, Glutapak-10, NutreStore, Resource, GlutaSolve, Sympt-X G.I., Sympt-X, Pyridoxine, G-CSF, Filgrastim, Neupogen, Stem cell transplant
Eligibility Criteria
Inclusion Criteria:
- Age 15-65
- Patients with: DLBCL with one of the following: 1. Primary refractory (no CR to 1st line); 2. High-risk relapse (CR1 <6 months, secondary IPI >1 or high LDH); or, 3. Refractory relapse: No response (SD or PD) to >/= 1 line of salvage.
- Hodgkin's with one of the following: 1. Primary refractory (no CR to 1st line or PD within 3 months); 2. High-risk relapse (CR1 <1 year, extranodal relapse or B symptoms); or, 3. Refractory relapse: No response (SD or PD) to >/= 1 line of salvage.
- T-NHL with one of the following: 1. Primary refractory (</= CR to 1st line or relapse within 6 months); or, 2. Nonresponsive (SD/PD) to >/= 1 line of salvage.
- 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 prior 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 enroll
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Cohort A: Diffuse Large B-Cell Lymphoma
Cohort B: Hodgkin's Lymphoma
Cohort C: T-Cell Lymphoma
Palifermin on Days -13 to -11 and on Days 0, +1, and +2. Panobinostat daily from Day -9 to -2. Gemcitabine administered on Days -8 and -3. Busulfan test dose administered on day -10. Doses of Days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1. Busulfan adjusted to target a cumulative AUC of 16000 and may be significantly higher or lower than 4000 on the last 2 days depending on first PK. Melphalan on Days -3 and -2. Rituximab on Day -9 for participants with CD20+ tumors. Dexamethasone twice a day from Day -8 AM to Day -2 PM. Caphosol oral rinses 30 mL four times a day used from Day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on Day -8. Pyridoxine three times a day from Day -1. Stem cells administered by vein on Day 0. G-CSF 1 time each day starting on Day +5 until blood cell levels return to normal.
Palifermin on Days -13 to -11 and on Days 0, +1, and +2. Panobinostat daily from Day -9 to -2. Gemcitabine administered on Days -8 and -3. Busulfan test dose administered on day -10. Doses of Days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1. Busulfan adjusted to target a cumulative AUC of 16000 and may be significantly higher or lower than 4000 on the last 2 days depending on first PK. Melphalan on Days -3 and -2. Rituximab on Day -9 for participants with CD20+ tumors. Dexamethasone twice a day from Day -8 AM to Day -2 PM. Caphosol oral rinses 30 mL four times a day used from Day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on Day -8. Pyridoxine three times a day from Day -1. Stem cells administered by vein on Day 0. G-CSF 1 time each day starting on Day +5 until blood cell levels return to normal.
Palifermin on Days -13 to -11 and on Days 0, +1, and +2. Panobinostat daily from Day -9 to -2. Gemcitabine administered on Days -8 and -3. Busulfan test dose administered on day -10. Doses of Days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1. Busulfan adjusted to target a cumulative AUC of 16000 and may be significantly higher or lower than 4000 on the last 2 days depending on first PK. Melphalan on Days -3 and -2. Rituximab on Day -9 for participants with CD20+ tumors. Dexamethasone twice a day from Day -8 AM to Day -2 PM. Caphosol oral rinses 30 mL four times a day used from Day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on Day -8. Pyridoxine three times a day from Day -1. Stem cells administered by vein on Day 0. G-CSF 1 time each day starting on Day +5 until blood cell levels return to normal.