Panobinostat (LBH589): Multiple Myeloma - Autologous Hematopoietic Cell Transplantation (HCT)

NCT02722941 | Completed Phase 2 Results

• 2 other identifiers: MCC-18430CLBH589DUS97T
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to learn more about ways to prevent or delay relapse of multiple myeloma (MM). This study will determine the best dosing schedule of LBH589 maintenance therapy as well as the safety (side effects) and tolerability of LBH589 maintenance therapy after autologous hematopoietic cell transplant (HCT).

Conditions

Multiple Myeloma

Keywords

autologous hematopoietic cell transplant (HCT); autologous

Outcome Measures

Primary Outcomes (1)

• Relative Dose Intensity (RDI) Per Cohort

  Investigators will calculate RDI for each cohort. Relative dose intensity (RDI) represents the ratio of the amount of a drug actually delivered \[actual dose intensity (DI)\] to the amount planned (planned DI). The purpose of calculating RDI is to evaluate whether the planned DI of a chemotherapy treatment was actually achieved which may suggest the feasibility of planned treatment regimen. There are multitude of reports demonstrating a correlation between RDI and survival in cancer treatment. RDI = (total dose received by the patient = mg)/(planned full dose of drug = mg).

  Up to 2 years

Secondary Outcomes (3)

• Complete Response Rate

  Up to 5 years

• Progression Free Survival (PFS)

  at 2 years

• Overall Survival (OS)

  at 2 years

Study Arms (2)

Cohort A: Maintenance Therapy

ACTIVE COMPARATOR

Panobinostat (LBH589): 20 mg by mouth three (3) times per week, every other week, of a 28-day schedule.

Drug: Panobinostat

Cohort B: Maintenance Therapy

ACTIVE COMPARATOR

Panobinostat (LBH589): 10 mg by mouth daily for seven (7) days, every other week, of a 28-day schedule.

Drug: Panobinostat

Interventions

Panobinostat DRUG

Maintenance therapy dosing as outlined in Cohorts A and B.

Also known as: LBH589

Cohort A: Maintenance Therapy; Cohort B: Maintenance Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients, age ≥ 18 years old
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Histologically confirmed diagnosis of multiple myeloma
• Meeting the Criteria for Symptomatic Multiple Myeloma (CRAB criteria) before the initiation of systemic chemotherapy
• Received high-dose melphalan (≥ 140 mg/m\^2) followed by autologous HCT based on the institutional guidelines and within +45 and +180 after autologous HCT at the time of panobinostat maintenance initiation
• Must have achieved at least partial response (PR) prior to autologous HCT and must not have progressive disease (PD) prior to the initiation of maintenance therapy
• Must meet the following laboratory criteria (prior to the initiation of panobinostat maintenance): Absolute neutrophil count (ANC) ≥ 1 x 10\^9/L; Hemoglobin ≥ 8 g/dl; Platelets ≥ 50 x 10\^9/L (without transfusion support); Creatinine clearance ≥ 40 ml/min or serum creatinine ≤ 2.5 x upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN; Serum bilirubin ≤ 1.5 x ULN; Albumin \> 3.0 g/dl; Clinically euthyroid. Note: Participants are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
• Baseline (pre-HCT) multigated acquisition (MUGA) or echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) ≥ the limit of normal (LLN) of the institutional normal
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 or Karnofsky performance status ≥ 70%
• Prior histone deacetylase (HDAC), deacetylase (DAC), HSP90 inhibitors or valproic acid for the treatment of cancer is allowed

You may not qualify if:

• Potential participants who have purely non-secretory multiple myeloma (i.e., the absence of a measurable protein in serum by electrophoresis and immunofixation and the absence of Bence-Jones protein in the urine defined by use of electrophoresis and immunofixation)
• Prior allogeneic HCT
• Prior solid organ transplant requiring immunosuppressive therapy
• Potential participants who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
• Impaired cardiac function or clinically significant cardiac diseases
• Diarrhea \> Common Terminology Criteria for Adverse Events (CTCAE) grade 2
• Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol
• Using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
• Have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies.
• Have received either immunotherapy within \< 8 weeks; chemotherapy within \< 4 weeks; or radiation therapy to \> 30% of marrow-bearing bone within \< 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies
• Have undergone major surgery ≤ 4 weeks prior to starting study drug or have not recovered from side effects of such therapy
• Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. WOCBP must have a negative serum pregnancy test within 24 hours of receiving the first dose of study medication.
• Male patients whose sexual partners are WOCBP not using effective birth control
• A prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
• Known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Taiga Nishihori, MD
• Organization: Moffitt Cancer Center

Taiga.Nishihori@moffitt.org

813-745-8156

Study Officials

• Taiga Nishihori, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2016
• First Posted: March 30, 2016
• Study Start: June 10, 2016
• Primary Completion: June 7, 2020
• Study Completion: January 18, 2021
• Last Updated: November 1, 2022
• Results First Posted: August 9, 2021

Record last verified: 2022-10

Locations

US (1)