Panobinostat/Bortezomib/Dexamethasone in Relapsed or Relapsed-and-refractory Multiple Myeloma (PANORAMA_3)

pharmaand

Status and phase: Completed; Phase 2

Conditions: Multiple Myeloma

Treatments: Drug: Bortezomib Injection; Drug: Panobinostat Capsules; Drug: Dexamethasone tablets

Study type: Interventional

Funder types: Industry

Identifiers

NCT02654990

2015-001564-19 (EudraCT Number)

CLBH589D2222

Details and patient eligibility

About

Note: The study data was transferred to zr pharma& following the divestment of panobinostat to pharma&. Prior to study completion under the sponsorship of Secura Bio, the study was initiated and conducted in part under the sponsorship of Novartis.

The purpose of this study is to investigate the safety and efficacy of 3 different regimens of panobinostat (20 milligrams [mg] thrice a week [TIW], 20 mg twice a week [BIW], and 10 mg TIW) in combination with subcutaneous bortezomib and dexamethasone and to provide exposure, safety and efficacy data to identify the optimal regimen of panobinostat in a randomized, 3-arm parallel design. This study will also assess the impact of administering subcutaneous bortezomib (in combination with panobinostat and dexamethasone) twice weekly for 4 cycles, and then weekly starting from Cycle 5 until disease progression in participants ≤ 75 years of age. Participants > 75 years of age will receive subcutaneous bortezomib weekly for the entire treatment period (in combination with panobinostat and dexamethasone) until disease progression.

Participants will be treated until disease progression or until they discontinue earlier due to unacceptable toxicity or for other reasons.

Participants who discontinued study treatment for reasons other than disease progression will be followed for efficacy every 6 weeks.

All participants will be followed for survival until the last participant entering long-term follow-up has completed a 3-year survival follow-up or discontinued earlier.

Enrollment: 248 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• multiple myeloma per International Myeloma Working Group 2014 definition
• requiring treatment for relapsed or relapsed/refractory disease
• measurable disease based on central protein assessment
• received 1 to 4 prior lines of therapy
• prior immunomodulatory agent(s) exposure
• acceptable lab values prior to randomization

Exclusion criteria

• primary refractory myeloma
• refractory to bortezomib
• concomitant anti-cancer therapy (other than bortezomib/dexamethasone and bisphosphonates)
• prior treatment with pan-deacetylase inhibitors
• clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months prior to randomization)
• unresolved diarrhea ≥ Common Terminology Criteria for adverse events grade 2 or presence of medical condition associated with chronic diarrhea (such as irritable bowel syndrome and inflammatory bowel disease)

Other protocol-defined inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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248 participants in 3 patient groups

Arm A - 20 mg Panobinostat TIW

Experimental group

Description:

20 mg panobinostat TIW, 2 weeks on/1 week off in combination with subcutaneous bortezomib and per oral dexamethasone

Treatment:

Drug: Dexamethasone tablets

Drug: Panobinostat Capsules

Drug: Bortezomib Injection

Arm B - 20 mg Panobinostat BIW

Experimental group

Description:

20 mg panobinostat BIW, 2 weeks on/1 week off in combination with subcutaneous bortezomib and per oral dexamethasone

Treatment:

Drug: Dexamethasone tablets

Drug: Panobinostat Capsules

Drug: Bortezomib Injection

Arm C - 10 mg Panobinostat TIW

Experimental group

Description:

10 mg panobinostat TIW, 2 weeks on/1 week off in combination with subcutaneous bortezomib and per oral dexamethasone

Treatment:

Drug: Dexamethasone tablets

Drug: Panobinostat Capsules

Drug: Bortezomib Injection