Study Stopped
Lack of funding
Panobinostat Combined With High-Dose Gemcitabine/Busulfan/Melphalan With Autologous Stem Cell Transplant for Patients With Refractory/Relapsed Lymphoma
2 other identifiers
interventional
N/A
0 countries
N/A
Brief Summary
The goal of this clinical research study is to learn about the safety and effectiveness of the combination of panobinostat, gemcitabine, busulfan, and melphalan, either with or without rituximab, in patients who have non-Hodgkin's or Hodgkin's lymphoma and are receiving a stem cell transplant.
Trial Health
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Started Jun 2017
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 9, 2016
CompletedFirst Posted
Study publicly available on registry
November 11, 2016
CompletedStudy Start
First participant enrolled
June 1, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2021
CompletedApril 21, 2017
April 1, 2017
4 years
November 9, 2016
April 20, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Event-Free Survival (EFS) in Participants with Diffuse Large B-Cell Lymphoma
EFS estimated by using the method of Kaplan and Meier.
2 years
Event-Free Survival (EFS) in Participants with Hodgkin's Lymphoma
EFS estimated by using the method of Kaplan and Meier.
2 years
Event-Free Survival (EFS) in Participants with T-Cell Lymphoma
EFS estimated by using the method of Kaplan and Meier.
2 years
Secondary Outcomes (2)
Treatment-Related Mortality (TRM)
100 days
Overall Survival (OS)
100 days
Study Arms (3)
Cohort A: Diffuse Large B-Cell Lymphoma
EXPERIMENTALPalifermin 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.
Cohort B: Hodgkin's Lymphoma
EXPERIMENTALPalifermin 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.
Cohort C: T-Cell Lymphoma
EXPERIMENTALPalifermin 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.
Interventions
Palifermin, per standard of care, on Days -13 to -11 and on Days 0, +1, and +2.
20 mg by mouth daily from Day -9 to -2.
Gemcitabine administered as a loading dose of 75 mg/m2 by vein followed by prolonged infusion over 4.5 hours of 2,700 mg/m2 (total daily dose 2,775 mg/m2) on Days -8 and -3.
Busulfan "test dose" administered on Day -10. Test dose of 32 mg/m2 based on actual body weight administrated over 60 minutes. Busulfan pharmacokinetics performed with the test dose and the first dose on Day-8. 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.
60 mg/m2 by vein on Days -3 and -2.
375 mg/m2 by vein on Day -9 for patients with CD20+ tumors.
8 mg by vein 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.
Oral cryotherapy (ice chips) from 30 minutes before until 2 hours after each Melphalan infusion.
100 mg by vein or mouth three times a day from Day -1.
Stem cells administered by vein on Day 0.
G-CSF administered as an injection just under the skin, per standard of care ,1 time each day starting on Day +5 until blood cell levels return to normal.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Yago Nieto, MD, PHD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 9, 2016
First Posted
November 11, 2016
Study Start
June 1, 2017
Primary Completion
June 1, 2021
Study Completion
June 1, 2021
Last Updated
April 21, 2017
Record last verified: 2017-04