MLN9708 (Ixazomib) in Combination With Panobinostat and Dexamethasone in Multiple Myeloma

NCT02057640 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: CASE4A13
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

This study will look at the safety and tolerability of the new drug MLN9708 in combination with the existing drugs panobinostat and dexamethasone among patients with relapsed or refractory multiple myeloma. This study will also look at the response and clinical benefit of the treatment and the progression-free survival and overall survival of study participants.

Conditions

Multiple Myeloma; Kahler Disease; Plasma-Cell Myeloma; Myelomatosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicity According to CTCAE Version 4.03

  Number of Participants with Dose Limiting Toxicity of MLN9708 (lxazomib) according to CTCAE version 4.03

  at 28 days from start of treatment

Secondary Outcomes (3)

• Response to Combination Therapy (Panobinostat, Dexamethasone, MLN9708)

  4 months (102 days)

• Progression-free Survival

  1 year from start of treatment

• Overall Survival

  up to 3 years from start of treatment

Study Arms (1)

Combination therapy: Panobinostat, dexamethasone, MLN9708

EXPERIMENTAL

Panobinostat: 20mg, on day 1, 3, 5, 15, 17, 19, 28 Dexamethasone: 20mg, on day 1, 2, 8, 9, 15, 16, 28 MLN9708: 4mg on day 1, 8, 15, 28

Drug: Panobinostat; Drug: Dexamethasone; Drug: MLN9708

Interventions

Panobinostat DRUG

20mg, on day 1, 3, 5, 15, 17, 19, 28

Combination therapy: Panobinostat, dexamethasone, MLN9708

Dexamethasone DRUG

20mg, on day 1, 2, 8, 9, 15, 16, 28

Combination therapy: Panobinostat, dexamethasone, MLN9708

MLN9708 DRUG

4mg on day 1, 8, 15, 28

Also known as: Ixazomib

Combination therapy: Panobinostat, dexamethasone, MLN9708

Eligibility Criteria

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

You may qualify if:

• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Patients must carry a diagnosis of symptomatic multiple myeloma according to international myeloma working group criteria and have relapsed or refractory disease according to international uniform response criteria and must have previously received therapy with a proteasome inhibitor and an IMiD™
• Must have measurable disease defined as any of the following: Serum m-spike ≥ 1g/dL, 24 h urine m-spike of at least 200mg/d, involved serum free light chains ≥ 100mg/L with abnormal serum free light chain ratio, bone marrow plasma cells of at least 30%
• ECOG PS ≤ 2
• No gastro-intestinal condition, that in the opinion of the treating physician or the principal investigator significantly limits oral absorption
• No serious uncontrolled coexisting medical condition
• Patients must meet the following laboratory criteria:
• ANC ≥ 1.0 x 10\^9/L without use of pegfilgrastim in the preceding 21 days and without non-pegylated G-CSF or GM-CSF within 7 days prior to study entry
• Hemoglobin ≥ 8 g/dl (may be after transfusion of packed red blood cells or use of erythropoiesis stimulating agents)
• Platelets ≥ 70x 10\^9/L without platelet transfusion 7 days prior to study entry
• AST and ALT ≤ 2.5 x ULN
• Serum bilirubin ≤ 1.5 x ULN
• Serum potassium ≥ LLN and serum magnesium ≥ LLN (electrolyte levels may be achieved with repletion or other supportive medications like potassium sparing diuretics)
• Creatinine clearance ≥ 30 mL/min according to Cockroft-Gault formula
• Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.

You may not qualify if:

• Prior anti-cancer treatment with MLN9708 (ixazomib), HDAC, DAC, HSP90 inhibitors or valproic acid
• Prior participation in a randomized controlled study that included MLN9708 (ixazomib) in one of the treatment arms independent of whether assigned to MLN9708 (ixazomib) or not
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
• History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible)
• Any history of ventricular fibrillation or torsade de pointes
• Bradycardia defined as HR\< 50 bpm. Patients with pacemakers are eligible if HR ≥ 50 bpm.
• Screening ECG with a QTcF \> 470 msec (QTcF=QT/3√RR). If potassium or magnesium blood levels are below normal limits, consider repeating ECG after correction of these electrolytes
• Right bundle branch block + left anterior hemiblock (bifascicular block)
• Patients with myocardial infarction or unstable angina ≤ 6 months prior to starting study drug
• Other clinically significant heart disease (e.g., CHF NY Heart Association class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
• Impairment of GI function or GI disease that may significantly alter the swallowing absorption of panobinostat and MLN9708
• Patients with diarrhea \> CTCAE (version 4.03) grade 2
• Patient has ≥ Grade 3 peripheral neuropathy, or ≥ Grade 2 with pain on clinical examination during the screening period.

Sponsors & Collaborators

• Jason Valent: lead

Study Sites (2)

University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Panobinostat; Dexamethasone; ixazomib

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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Jason Valent, MD
• Organization: Cleveland Clinic Taussig Cancer Center

valentj3@ccf.org

216-445-7238

Study Officials

• Jason Valent, MD

  Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• Ehsan Malek, MD

  Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: February 6, 2014
• First Posted: February 7, 2014
• Study Start: May 22, 2014
• Primary Completion: May 15, 2018
• Study Completion: May 15, 2018
• Last Updated: December 11, 2019
• Results First Posted: December 11, 2019

Record last verified: 2019-12

Locations

US (2)