Panobinostat in Combination With Daratumumab, Bortezomib and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma

NCT04956302 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-21005NCI-2021-04261
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the possible benefits and side effects of adding panobinostat to a combination of daratumumab, bortezomib and dexamethasone in treating patients with multiple myeloma that has come back (relapsed) or has not responded to treatment (refractory). Panobinostat may stop or slow multiple myeloma by blocking the growth of new blood vessels necessary for cancer growth. Giving panobinostat in combination with daratumumab, bortezomib and dexamethasone may work better in treating relapsed/refractory multiple myeloma.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

• Recommended phase 2 dose

  A standard "3+3" design will be used to determine the safe and tolerable dose level.

  End of cycle 1 (1 cycle = 28 days)

• Incidence of adverse events

  Assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

  Up to 3 years

Secondary Outcomes (6)

• Time to progression

  From start of treatment until objective tumor progression, assessed up to 3 years

• Progression-free survival

  From start of treatment until disease progression or death, assessed at 1 year

• Objective response rate (ORR)

  Up to 3 years

• Time to response

  From start of treatment until measurement criteria are first met for PR, very good partial response, or complete response, assessed up to 3 years

• Duration of overall response

  From the time measurement criteria are first met for partial response or better (whichever status is recorded first) until the first date of progressive disease or death, assessed up to 3 years

Other Outcomes (4)

• Plasma cell expression of CD38

  Baseline up to 60 days

• Changes in lymphocyte subsets with therapy

  Baseline up to 60 days

• Total number and ratio of regulatory T cells with CD38+ expression

  Baseline up to 60 days

Study Arms (1)

Treatment (panobinostat, daratumumab, bortezomib, dexa)

EXPERIMENTAL

Patients receive panobinostat PO QD on days 1, 3, 5, 15, 17, 19, daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles, bortezomib SC on days 1, 8, 15, 22 and dexamethasone PO (IV on days of daratumumab and hyaluronidase-fihj administration) QD on days 1, 8, 15, 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Bortezomib; Drug: Daratumumab and Hyaluronidase-fihj; Drug: Dexamethasone; Drug: Panobinostat Lactate

Interventions

Bortezomib DRUG

Given SC

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade

Treatment (panobinostat, daratumumab, bortezomib, dexa)

Daratumumab and Hyaluronidase-fihj DRUG

Given SC

Also known as: DARA Co-formulated with rHuPH20, DARA/rHuPH20, Daratumumab + rHuPH20, Daratumumab with rHuPH20, Daratumumab-rHuPH20, Daratumumab/Hyaluronidase-fihj, Daratumumab/rHuPH20 Co-formulation, Darzalex Faspro, Darzalex/rHuPH20, HuMax-CD38-rHuPH20, Recombinant Human Hyaluronidase Mixed with Daratumumab

Treatment (panobinostat, daratumumab, bortezomib, dexa)

Dexamethasone DRUG

Given PO or IV

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Treatment (panobinostat, daratumumab, bortezomib, dexa)

Panobinostat Lactate DRUG

Given PO

Also known as: Farydak

Treatment (panobinostat, daratumumab, bortezomib, dexa)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18-75 years of age with evidence of relapsed or refractory disease as defined by IMWG criteria and measurable disease as defined by any of the following:
• Serum M-protein \>= 0.5 g/dl (\>= 10 g/l)
• Urine monoclonal protein \>= 200 mg/24h
• Involved free light chain (FLC) level \>= 10mg/dl (\>= 100mg/l) and an abnormal serum free light chain ratio (\< 0.26, or \> 1.65)
• Patients must have had at least 1 prior line of therapy including lenalidomide or cyclophosphamide, V or other PI, with or without ASCT
• Patients with progressive disease (PD) as best response on V are excluded
• Patients with PD on D-based therapy may be eligible at the discretion of the treating physician
• Refractory (progressed on or within 120 days of treatment) to their last treatment
• Patients must be off last treatment for at least 2 weeks by the beginning of treatment on this protocol
• Hemoglobin \>= 7g/dL
• Absolute neutrophil count (ANC) \>= 1000/uL
• Platelets \>= 70,000/uL
• If plasma cell percentage on bone marrow biopsy aspirate or core is \> 30%, platelet requirement will be adjusted to 50,000/ul
• Total bilirubin \< 1.5 mg/dL
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase \< 2 x the upper limit of normal (ULN)

You may not qualify if:

• Patients with active (untreated or relapsed) central nervous system (CNS) metastasis of myeloma
• Patients with Waldenstrom macroglobulinemia, primary amyloid light-chain (AL) amyloidosis, primary plasma cell leukemia, or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
• Patients with secondary plasma cell leukemia are permitted
• Patients with peripheral neuropathy \> National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 2
• Patients receiving concurrent corticosteroids at the time protocol therapy is initiated other than for physiologic maintenance treatment
• Concurrent use of complementary or alternative medicines that would confound the interpretation of toxicities and antitumor activity of the study drugs
• Patients with known allergies, hypersensitivity, or intolerance to panobinostat, daratumumab, or bortezomib
• Unacceptable respiratory risk factors defined by any one of the following criteria:
• Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) less than 50% of predicted normal
• Moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification
• Unacceptable cardiac risk factors defined by any of the following criteria:
• Patients with congenital long QT syndrome
• Any history of ventricular fibrillation or torsade de pointes
• Bradycardia defined as heart rate (HR) \< 50 beats per minute (bpm)
• Left ventricular ejection fraction \< 30%

Sponsors & Collaborators

• Abdullah Khan: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; daratumumab; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; 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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Hydroxamic Acids; Hydroxylamines; Amines; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Abdullah M Khan, MBBS, MSc

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 30, 2021
• First Posted: July 9, 2021
• Study Start: September 27, 2021
• Primary Completion: June 16, 2022
• Study Completion: June 16, 2022
• Last Updated: June 6, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)