Panobinostat/Bortezomib/Dexamethasone in Relapsed or Relapsed-and-refractory Multiple Myeloma (PANORAMA_3)
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| ClinicalTrials.gov Identifier: NCT02654990 |
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Recruitment Status :
Active, not recruiting
First Posted : January 13, 2016
Last Update Posted : March 19, 2021
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The purpose of this study is to investigate the safety and efficacy of three different regimens of PAN (20 mg TIW, 20 mg BIW, and 10 mg TIW) in combination with s.c. BTZ and Dex and to provide exposure, safety and efficacy data to identify the optimal regimen of PAN in a randomized, 3-arm parallel design. This study will also assess the impact of administering s.c. BTZ (in combination with PAN and Dex) twice weekly for 4 cycles, and then weekly starting from Cycle 5 until disease progression in patients ≤ 75 years of age. Patients > 75 years of age will receive for the entire treatment period s.c. BTZ weekly (in combination with PAN and Dex) until disease progression.
Patients will be treated until disease progression or until they discontinue earlier due to unacceptable toxicity or for other reasons.
Patients who discontinued study treatment for reasons other than disease progression will be followed for efficacy every 6 weeks.
All patients will be followed for survival until the last patient entering long-term follow-up has completed a 3 year survival follow-up or discontinued earlier.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Myeloma | Drug: panobinostat capsules Drug: bortezomib injection Drug: dexamethasone tablets | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 249 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Multicenter, Randomized, Open-label Phase 2 Study Evaluating the Safety and Efficacy of Three Different Regimens of Oral Panobinostat in Combination With Subcutaneous Bortezomib and Oral Dexamethasone in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma Who Have Been Previously Exposed to Immunomodulatory Agents |
| Actual Study Start Date : | April 27, 2016 |
| Actual Primary Completion Date : | October 18, 2019 |
| Estimated Study Completion Date : | May 2, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm A - 20mg PAN TIW
20mg panobinostat three times a week, 2 weeks on/1week of in combination with s.c. bortezomib and p.o. dexamethasone
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Drug: panobinostat capsules
20mg, 10mg or 15mg (for dose reductions only)
Other Name: PAN, LBH589 Drug: bortezomib injection 1.3mg/m2 sub-cutaneous administration; Cycle 1-4: 2 weeks on/1 week off twice a week for patients <=75 years at time of screening; once a week for patient > 75 years Cycle 5+: once a week for all patients
Other Name: BTZ Drug: dexamethasone tablets pre and 24h after BTZ administration; patients <= 75 years at time of screening: 20mg/dose patients > 75 years: 10mg/dose
Other Name: Dex |
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Experimental: Arm B - 20mg PAN BIW
20mg panobinostat twice a week, 2 weeks on/1 week off in combination with s.c. bortezomib and p.o. dexamethasone
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Drug: panobinostat capsules
20mg, 10mg or 15mg (for dose reductions only)
Other Name: PAN, LBH589 Drug: bortezomib injection 1.3mg/m2 sub-cutaneous administration; Cycle 1-4: 2 weeks on/1 week off twice a week for patients <=75 years at time of screening; once a week for patient > 75 years Cycle 5+: once a week for all patients
Other Name: BTZ Drug: dexamethasone tablets pre and 24h after BTZ administration; patients <= 75 years at time of screening: 20mg/dose patients > 75 years: 10mg/dose
Other Name: Dex |
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Experimental: Arm C - 10mg PAN TIW
10mg panobinostat three times a week 2 weeks on/1 week off in combination with s.c. bortezomib and p.o. dexamethasone
|
Drug: panobinostat capsules
20mg, 10mg or 15mg (for dose reductions only)
Other Name: PAN, LBH589 Drug: bortezomib injection 1.3mg/m2 sub-cutaneous administration; Cycle 1-4: 2 weeks on/1 week off twice a week for patients <=75 years at time of screening; once a week for patient > 75 years Cycle 5+: once a week for all patients
Other Name: BTZ Drug: dexamethasone tablets pre and 24h after BTZ administration; patients <= 75 years at time of screening: 20mg/dose patients > 75 years: 10mg/dose
Other Name: Dex |
- Overall response rate (ORR) up to 8 cycles [ Time Frame: up to 8 cycles per patient, approximately 30 months ]assessed according to IMWG guidelines
- ORR throughout study [ Time Frame: approximately 70 months ]
- individual immunophenotypic complete response (CR) rate [ Time Frame: approximately 30 and 70 months ]
- Progression-free survival [ Time Frame: approximately 30 and 70 months ]
- Maximum plasma concentration (Cmax) for panobinostat (PAN) and bortezomib (BTZ) [ Time Frame: approximately 30 months ]
- Time to progression [ Time Frame: approximately 30 and 70 months ]
- Time to response [ Time Frame: approximately 30 and 70 months ]
- Duration of response (DOR) [ Time Frame: approximately 30 and 70 months ]
- European Organization of Research and Treatment of Cancer Quality of Life core 30-item questionnaire scores over time compared [ Time Frame: approximately 30 and 70 months ]EORTC QLQ-C30 on-treatment and in post treatment follow-up
- individual stringent CR rate [ Time Frame: approximately 30 and 70 months ]
- individual CR rate [ Time Frame: approximately 30 and 70 months ]
- overall survival [ Time Frame: approximately 30 and 70 months ]
- individual Very Good Partial Response rate [ Time Frame: approximately 30 and 70 months ]
- Functional Assessment of Cancer Therapy / Gynecologic Oncology Group - Neurotoxicity scale scores over time [ Time Frame: approximately 30 and 70 months ]FACT/GOG-Ntx on-treatment
- Time to reach Cmax for PAN and BTZ [ Time Frame: approximately 30 months ]
- Minimum observed plasma concentration (Cmin) for PAN and BTZ [ Time Frame: approximately 30 months ]
- Observed plasma concentration 24 hours after single and multiple dose administration of PAN and BTZ [ Time Frame: 24 hours after every dose, approximately 30 months ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- multiple myeloma as per IMWG 2014 definition
- requiring treatment for relapsed or relapsed/refractory disease
- measurable disease based on central protein assessment
- 1 to 4 prior lines of therapy
- prior IMiD exposure
- acceptable lab values prior to randomization
Exclusion Criteria:
- primary refractory myeloma
- refractory to bortezomib
- concomitant anti-cancer therapy (other then BTZ/Dex and bisphosphonates)
- prior treatment with DAC inhibitors
- clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months prior to randomization)
- unresolved diarrhea ≥ CTCAE grade 2 or presence of medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease)
Other protocol-defined inclusion/exclusion criteria may apply.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02654990
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| Study Director: | SecuraBio | SecuraBio |
| Responsible Party: | SecuraBio |
| ClinicalTrials.gov Identifier: | NCT02654990 |
| Other Study ID Numbers: |
CLBH589D2222 |
| First Posted: | January 13, 2016 Key Record Dates |
| Last Update Posted: | March 19, 2021 |
| Last Verified: | March 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Plan Description: | Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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multiple myeloma relapsed or relapsed/refractory LBH589 |
panobinostat bortezomib dexamethasone |
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Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Dexamethasone |
Bortezomib Panobinostat Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Histone Deacetylase Inhibitors Enzyme Inhibitors |