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Panobinostat Combined With High-Dose Gemcitabine/Busulfan/Melphalan With Autologous Stem Cell Transplant for Patients With Refractory/Relapsed Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02961816
Recruitment Status : Withdrawn (Lack of funding)
First Posted : November 11, 2016
Last Update Posted : April 21, 2017
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
Lymphoma Drug: Palifermin Drug: Panobinostat Drug: Gemcitabine Drug: Busulfan Drug: Melphalan Drug: Rituximab Drug: Dexamethasone Drug: Caphosol Drug: Glutamine Other: Oral Cryotherapy (ice chips) Drug: Pyridoxine Biological: Stem Cell Infusion Drug: G-CSF Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Panobinostat Combined With High-Dose Gemcitabine/Busulfan/Melphalan With Autologous Stem Cell Transplant for Patients With Refractory/Relapsed Lymphoma
Estimated Study Start Date : June 2017
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021


Arm Intervention/treatment
Experimental: Cohort A: Diffuse Large B-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.

Drug: Palifermin
Palifermin, per standard of care, on Days -13 to -11 and on Days 0, +1, and +2.
Other Name: Kepivance

Drug: Panobinostat
20 mg by mouth daily from Day -9 to -2.
Other Name: LBH589B

Drug: Gemcitabine
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.
Other Names:
  • Gemcitabine Hydrochloride
  • Gemzar

Drug: Busulfan
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.
Other Names:
  • Busulfex
  • Myleran

Drug: Melphalan
60 mg/m2 by vein on Days -3 and -2.
Other Name: Alkeran

Drug: Rituximab
375 mg/m2 by vein on Day -9 for patients with CD20+ tumors.
Other Name: Rituxan

Drug: Dexamethasone
8 mg by vein twice a day from Day -8 AM to Day -2 PM.
Other Name: Decadron

Drug: Caphosol
Caphosol oral rinses 30 mL four times a day used from Day -8.

Drug: Glutamine
Oral Glutamine, 15 g four times a day, swished, gargled and swallowed started on Day -8.
Other Names:
  • Enterex
  • Glutapak-10
  • NutreStore
  • Resource
  • GlutaSolve
  • Sympt-X G.I.
  • Sympt-X

Other: Oral Cryotherapy (ice chips)
Oral cryotherapy (ice chips) from 30 minutes before until 2 hours after each Melphalan infusion.

Drug: Pyridoxine
100 mg by vein or mouth three times a day from Day -1.

Biological: Stem Cell Infusion
Stem cells administered by vein on Day 0.
Other Name: Stem Cell Transplant

Drug: G-CSF
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.
Other Names:
  • Filgrastim
  • Neupogen

Experimental: Cohort B: Hodgkin's 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.

Drug: Palifermin
Palifermin, per standard of care, on Days -13 to -11 and on Days 0, +1, and +2.
Other Name: Kepivance

Drug: Panobinostat
20 mg by mouth daily from Day -9 to -2.
Other Name: LBH589B

Drug: Gemcitabine
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.
Other Names:
  • Gemcitabine Hydrochloride
  • Gemzar

Drug: Busulfan
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.
Other Names:
  • Busulfex
  • Myleran

Drug: Melphalan
60 mg/m2 by vein on Days -3 and -2.
Other Name: Alkeran

Drug: Rituximab
375 mg/m2 by vein on Day -9 for patients with CD20+ tumors.
Other Name: Rituxan

Drug: Dexamethasone
8 mg by vein twice a day from Day -8 AM to Day -2 PM.
Other Name: Decadron

Drug: Caphosol
Caphosol oral rinses 30 mL four times a day used from Day -8.

Drug: Glutamine
Oral Glutamine, 15 g four times a day, swished, gargled and swallowed started on Day -8.
Other Names:
  • Enterex
  • Glutapak-10
  • NutreStore
  • Resource
  • GlutaSolve
  • Sympt-X G.I.
  • Sympt-X

Other: Oral Cryotherapy (ice chips)
Oral cryotherapy (ice chips) from 30 minutes before until 2 hours after each Melphalan infusion.

Drug: Pyridoxine
100 mg by vein or mouth three times a day from Day -1.

Biological: Stem Cell Infusion
Stem cells administered by vein on Day 0.
Other Name: Stem Cell Transplant

Drug: G-CSF
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.
Other Names:
  • Filgrastim
  • Neupogen

Experimental: 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.

Drug: Palifermin
Palifermin, per standard of care, on Days -13 to -11 and on Days 0, +1, and +2.
Other Name: Kepivance

Drug: Panobinostat
20 mg by mouth daily from Day -9 to -2.
Other Name: LBH589B

Drug: Gemcitabine
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.
Other Names:
  • Gemcitabine Hydrochloride
  • Gemzar

Drug: Busulfan
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.
Other Names:
  • Busulfex
  • Myleran

Drug: Melphalan
60 mg/m2 by vein on Days -3 and -2.
Other Name: Alkeran

Drug: Rituximab
375 mg/m2 by vein on Day -9 for patients with CD20+ tumors.
Other Name: Rituxan

Drug: Dexamethasone
8 mg by vein twice a day from Day -8 AM to Day -2 PM.
Other Name: Decadron

Drug: Caphosol
Caphosol oral rinses 30 mL four times a day used from Day -8.

Drug: Glutamine
Oral Glutamine, 15 g four times a day, swished, gargled and swallowed started on Day -8.
Other Names:
  • Enterex
  • Glutapak-10
  • NutreStore
  • Resource
  • GlutaSolve
  • Sympt-X G.I.
  • Sympt-X

Other: Oral Cryotherapy (ice chips)
Oral cryotherapy (ice chips) from 30 minutes before until 2 hours after each Melphalan infusion.

Drug: Pyridoxine
100 mg by vein or mouth three times a day from Day -1.

Biological: Stem Cell Infusion
Stem cells administered by vein on Day 0.
Other Name: Stem Cell Transplant

Drug: G-CSF
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.
Other Names:
  • Filgrastim
  • Neupogen




Primary Outcome Measures :
  1. Event-Free Survival (EFS) in Participants with Diffuse Large B-Cell Lymphoma [ Time Frame: 2 years ]
    EFS estimated by using the method of Kaplan and Meier.

  2. Event-Free Survival (EFS) in Participants with Hodgkin's Lymphoma [ Time Frame: 2 years ]
    EFS estimated by using the method of Kaplan and Meier.

  3. Event-Free Survival (EFS) in Participants with T-Cell Lymphoma [ Time Frame: 2 years ]
    EFS estimated by using the method of Kaplan and Meier.


Secondary Outcome Measures :
  1. Treatment-Related Mortality (TRM) [ Time Frame: 100 days ]
    (TRM) monitored by using the method of Thall, Simon, and Estey.

  2. Overall Survival (OS) [ Time Frame: 100 days ]
    OS estimated by using the method of Kaplan and Meier.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   15 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 15-65
  2. 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.
  3. 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.
  4. 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.
  5. Adequate renal function, as defined by estimated serum creatinine clearance >/= 50 ml/min and/or serum creatinine </= 1.8 mg/dL
  6. Adequate hepatic function (SGOT and/or serum glutamate pyruvate transaminase (SGPT) </= 3 x upper limit of normal (ULN); bilirubin and ALP </= 2 x ULN
  7. 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%
  8. Adequate cardiac function with left ventricular ejection fraction >/= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease
  9. PS <2
  10. Negative Beta human chorionic gonadotropin (HCG) in woman with child-bearing potential

Exclusion Criteria:

  1. Grade >/= 3 non-hematologic toxicity from prior therapy that has not resolved to </= G1
  2. Prior whole brain irradiation
  3. Corrected QT interval (QTc) longer than 500 ms
  4. Active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA >/= 10,000 copies/mL, or >/= 2,000 IU/mL)
  5. Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology
  6. Active infection requiring parenteral antibiotics
  7. HIV infection, unless receiving effective antiretroviral therapy with undetectable viral load and normal cluster of differentiation 4 (CD4) counts
  8. Radiation therapy in the month prior to enroll

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02961816


Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Layout table for investigator information
Principal Investigator: Yago Nieto, MD, PHD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02961816     History of Changes
Other Study ID Numbers: 2016-0074
NCI-2016-01914 ( Registry Identifier: NCI CTRP )
First Posted: November 11, 2016    Key Record Dates
Last Update Posted: April 21, 2017
Last Verified: April 2017

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pyridoxine
Pyridoxal
Vitamin B 6
Gemcitabine
Dexamethasone
Dexamethasone acetate
Rituximab
Melphalan
Busulfan
Panobinostat
BB 1101
Lenograstim
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents