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

April 20, 2017 updated by: M.D. Anderson Cancer Center
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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Busulfan Test Dose:

Participant will receive a test dose of busulfan by vein over about 60 minutes. Before and after participant receives this low-level test dose of busulfan, blood will be drawn several times to check how the level of busulfan in participant's blood changes over time. This is called pharmacokinetic (PK) testing. This information will be used to decide the next dose needed to reach the correct blood level that matches participant's body size. Participant will most likely receive this test dose as an outpatient during the week before participant is admitted to the hospital. If it cannot be given as an outpatient, participant will be admitted to the hospital on Day -11 (11 days before participant's stem cells are returned to participant's body) and the test dose will be given on Day -10.

Blood (about 1 teaspoon each time) will be drawn for PK testing about 11 times before participant's test dose of busulfan and 10 times over the 11 hours after the dose. The blood samples will be repeated again on the first day of high-dose busulfan treatment (Day -8). A temporary heparin lock line will be placed in participant's vein to lower the number of needle sticks needed for these draws.

If it is not possible for the PK tests to be performed for any reason, participant will receive the standard fixed dose of busulfan.

Study Drug Administration:

On Days -13 through -11 (the 3 days before participant is admitted to the hospital), participant will receive palifermin by vein over about 30 seconds each day to help decrease the risk of side effects in the mouth and throat.

On Day -9 through Day -2, participant will take panobinostat by mouth, with food. The study staff will tell participant how many tablets to take. Participant will receive dexamethasone by vein over about 3-5 minutes 2 times each day.

On Day -9, if participant has a type of B-cell cancer, participant will receive rituximab (a treatment used for certain lymphomas) by vein over about 3-6 hours as part of participant's standard care. The study doctor will tell participant if participant will receive rituximab.

On Day -8, participant will receive gemcitabine by vein over 4½ hours.

On Days -8, -7, -6, and -5, participant will receive busulfan by vein over about 60 minutes.

On Day -3, participant will receive gemcitabine by vein over 4½ hours and then melphalan by vein over 30 minutes.

On Day -2, participant will receive melphalan by vein over 30 minutes.

On Day -1, participant will rest (participant will not receive chemotherapy).

On Day 0, participant will receive participant's stem cells by vein over about 30-60 minutes.

Participant will receive 3 more doses of palifermin by vein, over 15-30 seconds each time, on Days 0, +1, and +2.

As part of standard care, participant will receive G-CSF (filgrastim) as an injection just under participant's skin 1 time each day starting on Day +5 until participant's blood cell levels return to normal. The study doctor will discuss this with participant, including how filgrastim is given and its risks.

Length of Study:

As part of standard care, participant will remain in the hospital for about 3-4 weeks after the transplant. After participant is released from the hospital, participant will continue as an outpatient. Participant will need to stay in the Houston area to be checked for infections and side effects.

Participant will be taken off study about 100 days after the transplant. Participant may be taken off study earlier if the disease gets worse, if intolerable side effects occur, or if participant is unable to follow study directions.

Study Tests:

About 100 days after the transplant:

  • Participant will have a physical exam.
  • Blood (about 4 teaspoons) and urine will be collected for routine tests.
  • If the doctor thinks it is needed, participant may have a bone marrow aspiration and biopsy to check the status of the disease. To collect a bone marrow aspiration/biopsy, an area of the hip is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.

This is an investigational study. Panobinostat and melphalan are FDA approved and commercially available for the treatment of multiple myeloma (MM). Busulfan is FDA approved and commercially available for the treatment of leukemia. Gemcitabine is FDA approved and commercially available for the treatment of lymphoma, breast cancer, and lung cancer. Rituximab is FDA approved and commercially available for the treatment of non-Hodgkin's lymphoma.

The use of these study drugs in combination is investigational. The study doctor can explain how the study drugs are designed to work.

Up to 75 participants will take part in this study. All will be enrolled at MD Anderson.

Study Type

Interventional

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

11 years to 61 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Kepivance
Drug: Panobinostat
20 mg by mouth daily from Day -9 to -2.
Other Names:
  • 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:
  • Gemzar
  • Gemcitabine Hydrochloride
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 Names:
  • Alkeran
Drug: Rituximab
375 mg/m2 by vein on Day -9 for patients with CD20+ tumors.
Other Names:
  • Rituxan
Drug: Dexamethasone
8 mg by vein twice a day from Day -8 AM to Day -2 PM.
Other Names:
  • 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 Names:
  • 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 Names:
  • Kepivance
Drug: Panobinostat
20 mg by mouth daily from Day -9 to -2.
Other Names:
  • 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:
  • Gemzar
  • Gemcitabine Hydrochloride
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 Names:
  • Alkeran
Drug: Rituximab
375 mg/m2 by vein on Day -9 for patients with CD20+ tumors.
Other Names:
  • Rituxan
Drug: Dexamethasone
8 mg by vein twice a day from Day -8 AM to Day -2 PM.
Other Names:
  • 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 Names:
  • 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 Names:
  • Kepivance
Drug: Panobinostat
20 mg by mouth daily from Day -9 to -2.
Other Names:
  • 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:
  • Gemzar
  • Gemcitabine Hydrochloride
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 Names:
  • Alkeran
Drug: Rituximab
375 mg/m2 by vein on Day -9 for patients with CD20+ tumors.
Other Names:
  • Rituxan
Drug: Dexamethasone
8 mg by vein twice a day from Day -8 AM to Day -2 PM.
Other Names:
  • 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 Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 years
Event-Free Survival (EFS) in Participants with Hodgkin's Lymphoma
Time Frame: 2 years
EFS estimated by using the method of Kaplan and Meier.
2 years
Event-Free Survival (EFS) in Participants with T-Cell Lymphoma
Time Frame: 2 years
EFS estimated by using the method of Kaplan and Meier.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment-Related Mortality (TRM)
Time Frame: 100 days
(TRM) monitored by using the method of Thall, Simon, and Estey.
100 days
Overall Survival (OS)
Time Frame: 100 days
OS estimated by using the method of Kaplan and Meier.
100 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 1, 2017

Primary Completion (Anticipated)

June 1, 2021

Study Completion (Anticipated)

June 1, 2021

Study Registration Dates

First Submitted

November 9, 2016

First Submitted That Met QC Criteria

November 9, 2016

First Posted (Estimate)

November 11, 2016

Study Record Updates

Last Update Posted (Actual)

April 21, 2017

Last Update Submitted That Met QC Criteria

April 20, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-0074
  • NCI-2016-01914 (Registry Identifier: NCI CTRP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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