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LymphomaPhase 2NCT02961816

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

A Phase 2 study testing Palifermin, Panobinostat and Gemcitabine in people with Lymphoma, run by M.D. Anderson Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 15 to 65 years
Conditions the study is for
Lymphoma
What is being tested?
Palifermin, Panobinostat and Gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Jun 2017to Jun 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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

About this study

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.

Read the 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.

Conditions
Lymphoma
Being tested
Palifermin, Panobinostat, Gemcitabine, Busulfan, Melphalan
Keywords
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
Medical subject headings
Lymphoma, Lymphoma, Large B-Cell, Diffuse, Hodgkin Disease, Lymphoma, T-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PaliferminDrug

    Also called Kepivance

    Palifermin, per standard of care, on Days -13 to -11 and on Days 0, +1, and +2.

  • PanobinostatDrug

    Also called LBH589B

    20 mg by mouth daily from Day -9 to -2.

  • GemcitabineDrug

    Also called Gemcitabine Hydrochloride, Gemzar

    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.

  • BusulfanDrug

    Also called Busulfex, Myleran

    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.

  • MelphalanDrug

    Also called Alkeran

    60 mg/m2 by vein on Days -3 and -2.

  • RituximabDrug

    Also called Rituxan

    375 mg/m2 by vein on Day -9 for patients with CD20+ tumors.

  • DexamethasoneDrug

    Also called Decadron

    8 mg by vein twice a day from Day -8 AM to Day -2 PM.

  • CaphosolDrug

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

  • GlutamineDrug

    Also called Enterex, Glutapak-10, NutreStore, Resource

    Oral Glutamine, 15 g four times a day, swished, gargled and swallowed started on Day -8.

  • Oral Cryotherapy (ice chips)Other

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

  • PyridoxineDrug

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

  • Stem Cell InfusionBiological

    Also called Stem Cell Transplant

    Stem cells administered by vein on Day 0.

  • G-CSFDrug

    Also called Filgrastim, Neupogen

    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.

Study groups in NCT02961816
Study groupRoleWhat they receive
Cohort A: Diffuse Large B-Cell LymphomaExperimentalPalifermin 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.
Receives: 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
Cohort B: Hodgkin's LymphomaExperimentalPalifermin 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.
Receives: 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
Cohort C: T-Cell LymphomaExperimentalPalifermin 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-Free Survival (EFS) in Participants with Diffuse Large B-Cell Lymphoma

    EFS estimated by using the method of Kaplan and Meier.

    Measured: 2 years

  2. Event-Free Survival (EFS) in Participants with Hodgkin's Lymphoma

    EFS estimated by using the method of Kaplan and Meier.

    Measured: 2 years

  3. Event-Free Survival (EFS) in Participants with T-Cell Lymphoma

    EFS estimated by using the method of Kaplan and Meier.

    Measured: 2 years

Secondary outcomes (2)

  1. Treatment-Related Mortality (TRM)

    (TRM) monitored by using the method of Thall, Simon, and Estey.

    Measured: 100 days

  2. Overall Survival (OS)

    OS estimated by using the method of Kaplan and Meier.

    Measured: 100 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Nov 2016 (estimated)
  2. Study startJun 2017 (estimated)
  3. Primary completionJun 2021 (estimated)
  4. Study completionJun 2021 (estimated)

Why it stopped: Lack of funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02961816
Sponsor's protocol ID
2016-0074
Other IDs
NCI-2016-01914
Status last verified
Apr 2017
First submitted
9 Nov 2016
Last updated
21 Apr 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Palifermin, Panobinostat and Gemcitabine in people with Lymphoma, run by M.D. Anderson Cancer Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 21 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-Free Survival (EFS) in Participants with Diffuse Large B-Cell Lymphoma (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02961816.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2017.

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