Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma (PANORAMA-1)

Novartis

Status and phase: Completed; Phase 3

Conditions: Multiple Myeloma

Treatments: Drug: Dexamethasone; Drug: Panobinostat; Drug: Placebo; Drug: Bortezomib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01023308

CLBH589D2308

2009-015507-52 (EudraCT Number)

Details and patient eligibility

About

Panobinostat (LBH589) is a highly potent pan-deacetylase inhibitor (pan-DACi), inclusive of HDAC6, which disrupts aggresome function, promotes accumulation of cytotoxic misfolded protein aggregates and triggers myeloma cell death. Combination of pan-DAC and protease inhibition by co-treatment with panobinostat (PAN) and bortezomib (BTZ) has demonstrated synergistic cytotoxicity in vitro and in vivo in pre-clinical experiments. Furthermore, clinical experience in advanced multiple myeloma (MM) patients treated by oral panobinostat and i.v bortezomib ± dexamethasone showed very encouraging results for efficacy and manageable toxicity profile.

Given the medical need for improved treatment strategies for patients with previously treated and relapsed MM, the purpose of this prospective, multinational, randomized, double-blind, placebo-controlled, parallel group Phase III study is to compare the results in progression-free survival of 2 combination therapies, panobinostat with bortezomib and dexamethasone or placebo with bortezomib and dexamethasone, in patients with previously treated MM whose disease has recurred or progressed.

Enrollment: 767 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patient has a previous diagnosis of multiple myeloma.
2. Patient requires retreatment for multiple myeloma
3. Patient has measurable M component in serum or urine at study screening

Exclusion criteria

1. Patient who has progressed under all prior lines of anti MM therapy
2. Patient who has been treated by bortezomib before, and did not reach at least a minor response under this therapy, or progressed under it or within 60 days of last dose
3. Patient has shown intolerance to bortezomib or to dexamethasone or components of these drugs or has any contraindication to one or the other drug , following locally applicable prescribing information
4. Patient received prior treatment with DAC inhibitors including panobinostat
5. Patient has impaired cardiac function, or a prolonged QTc interval at screening ECG
6. Patient taking medications with relative risk of prolonging the QT interval or inducing Torsade de pointes
7. Female patient who is pregnant or breast feeding or with childbearing potential and not willing to use a double method of contraception up to 3 months after the end of study treatment. Male patient who is not willing to use a barrier method of contraception up to 3 months after the end of study treatment.

Other protocol-defined inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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767 participants in 2 patient groups, including a placebo group

Panobinostat + Bortezomib + Dexamethasone

Experimental group

Treatment:

Drug: Bortezomib

Drug: Dexamethasone

Drug: Panobinostat

Placebo + Bortezomib + Dexamethasone

Placebo Comparator group

Treatment:

Drug: Placebo

Drug: Bortezomib

Drug: Dexamethasone