Hodgkin's Lymphoma
Conditions
Keywords
Phase III randomized, double blind, placebo controlled multi-center study, panobinostat, Hodgkin's lymphoma, at risk for relapse, autologous stem cell transplant
Brief summary
The primary objective was to provide drug to ongoing patients who were receiving panobinostat and to characterize the safety and tolerability of panobinostat in patients with HL after achieving a complete response following autologous hematopoietic stem cell transplant (AHSCT) with high dose chemotherapy (HDT). Primary objective as stated above reflects a change from the original protocol as of an amendment. The original objective was no longer feasible with only 41 of 367 patients randomized after the study was halted due to poor recruitment. An amendment was written to allow patients on panobinostat to continue their treatment until discontinuation/completion criteria were met (patients were unblinded). Therefore, the study was completed as per this amendment. No secondary objectives were included for this trial from the amendment; this was a change from the original protocol.
Interventions
DRUGPanobinostat
DRUGPlacebo
Placebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient age is greater than or equal to 18 years 2. Patient has a history of histologically confirmed classical HL (i.e. Nodular sclerosing (NSHL), Mixed-cellularity (MCHL), Lymphocyte-rich (LRHL), Lymphocyte depleted (LDHL)) 3. Patient has achieved a complete response by CT/MRI scan within 9 weeks (± 1 week) from the day of their first autologous peripheral blood/ bone marrow stem cell transfusion (AHSCT) following HDT. Complete response is defined as: Normalization of all nodes and lesions compared to pre-transplant scan performed prior to salvage therapy for relapse. Any residual abnormal masses on the post transplant CT/MRI must be metabolically inactive on a PET scan. 4. Patient has at least one of the following factors that places them at risk for relapse: * Primary refractory disease (including relapse in ≤ 3 months of completion of 1st line treatment) * First relapse \>3 but \<12 months from last dose of 1st line treatment * Multiple relapses (prior to transplant) * Stage III/IV disease (at relapse, prior to transplant) * Hemoglobin \<10.5 gm/dL (at relapse, prior to transplant)
Exclusion criteria
Patient has been treated with allogeneic transplant 2. Patient has received any anti-lymphoma therapy after AHSCT including but not limited to: * chemotherapy prior to start of study * biologic immunotherapy including monoclonal antibodies or experimental therapy prior to start of study * radiation therapy 3. Patient has not recovered from reversible toxicity due to any prior therapies (e.g. returned to baseline or Grade ≤1) except for hematological laboratory parameters Note: Patient does not meet this criteria if the toxicity is stable and irreversible, and there is no evidence that panobinostat causes a similar toxicity 4. Patient has received prior treatment with DAC inhibitors including panobinostat
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 23 months | Safety monitoring was conducted throughout the study. |
Countries
Australia, Belgium, Brazil, Canada, France, Germany, Israel, Italy, Netherlands, New Zealand, Poland, Russia, Singapore, United States
Participant flow
Recruitment details
Participants were randomized in a 2:1 ratio to the PAN and placebo groups, respectively.
Participants by arm
| Arm | Count |
|---|---|
| Panobinostat (PAN) Participants received 45 mg orally 3 times a week (TIW), every other week (QOW). | 27 |
| Placebo Participants received matching placebo to PAN TIW, QOW. | 14 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory value | 1 | 0 |
| Overall Study | Administrative problems | 0 | 1 |
| Overall Study | Adverse Event | 6 | 0 |
| Overall Study | Disease progression | 3 | 4 |
| Overall Study | Protocol deviation | 1 | 0 |
| Overall Study | Treatment completed as per protocol | 8 | 7 |
| Overall Study | Withdrawal by Subject | 8 | 2 |
Baseline characteristics
| Characteristic | Panobinostat (PAN) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 34.0 Years STANDARD_DEVIATION 10.72 | 30.6 Years STANDARD_DEVIATION 10.56 | 32.9 Years STANDARD_DEVIATION 10.66 |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 19 Participants | 7 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 26 / 26 | 11 / 12 |
| serious Total, serious adverse events | 2 / 26 | 1 / 12 |
Outcome results
Primary
Number of Participants With Adverse Events
Safety monitoring was conducted throughout the study.
Time frame: 23 months
Population: Safety set: The safety set included randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panobinostat (PAN) | Number of Participants With Adverse Events | 26 Participants |
| Placebo | Number of Participants With Adverse Events | 11 Participants |