A Study of Ixazomib, Thalidomide and Dexamethasone in Newly Diagnosed and Treatment-naive Multiple Myeloma (MM) Participants Non-eligible for Autologous Stem-cell Transplantation

NCT03608501 | Withdrawn Phase 2 DMC

• 2 other identifiers: C16041U1111-1214-1078
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 6

Brief Summary

The primary purpose of this study is to determine the overall response rate (ORR) during induction therapy with the combination of ixazomib, thalidomide and low-dose dexamethasone in specific time points.

Conditions

Multiple Myeloma

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• ORR During Induction

  ORR is the percentage of participants with presence of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). ORR assessment will be based on International Myeloma Working Group (IMWG) response criteria.

  Upon ORR assessment during specific timepoints for all participants completing or withdrawn prematurely from the induction phase (Baseline up to approximately 9 month [Cycle 9])

Secondary Outcomes (4)

• Progression-free Survival (PFS)

  Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 2 years])

• ORR During Maintenance

  Upon ORR assessment during specific time points for all participants completing or withdrawn prematurely from maintenance phase (Baseline up to approximately 2 years)

• Overall Survival (OS)

  Upon study termination (Baseline up to approximately 5 years)

• Time to Response During Induction

  End of induction phase (Baseline up to approximately 9 months [Cycle 9])

Study Arms (1)

Ixazomib 4 mg + Thalidomide 100 mg + Dexamethasone 40 mg

EXPERIMENTAL

Ixazomib 4 milligram (mg), capsule, orally, once on Days 1, 8 and 15 along with thalidomide 100 mg, tablet, orally, once daily and dexamethasone 40 mg, tablet, orally, once on Days 1, 8, 15 and 22 in a 28-day treatment cycle for up to 9 cycles or until withdrawal from the study in the treatment phase. Participants who complete treatment phase will be eligible to continue on to the maintenance phase of the study to receive ixazomib 4 mg, capsules, orally, once on Days 1, 8 and 15 of a 28-day treatment cycle for up to 24 months or until withdrawal from the study.

Drug: Ixazomib; Drug: Thalidomide; Drug: Dexamethasone

Interventions

Ixazomib DRUG

Ixazomib capsules.

Also known as: Ixazomib citrate

Ixazomib 4 mg + Thalidomide 100 mg + Dexamethasone 40 mg

Thalidomide DRUG

Thalidomide capsules.

Ixazomib 4 mg + Thalidomide 100 mg + Dexamethasone 40 mg

Dexamethasone DRUG

Dexamethasone tablets.

Ixazomib 4 mg + Thalidomide 100 mg + Dexamethasone 40 mg

Eligibility Criteria

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

You may qualify if:

• Clonal bone marrow plasma cells \>=10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events:
• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
• Hypercalcaemia: serum calcium greater than (\>) 1 mg/dL higher than the upper limit of normal (ULN) or \>11 mg/dL;
• Renal insufficiency: creatinine clearance \<40 milliliter (mL) per minute (as per validated equations) or serum creatinine \>2 mg/dL;
• Anemia: haemoglobin value of \>20 gram per liter (g/L) below the lower limit of normal, or a haemoglobin value \<100 g/L;
• Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)-CT.
• Any one or more of the following biomarkers of malignancy:
• Clonal bone marrow plasma cell percentage \>=60%.
• Involved: uninvolved serum free light chain ratio \>=100.
• Greater than (\>) 1 focal lesions on magnetic resonance imaging (MRI) studies. Note: clonality should be established by showing kappa to lambda ratio (κ/λ)-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used.
• Ineligibility to autologous transplantation, as per investigator's discretion, regardless of age (the reason for such ineligibility should be recorded on the electronic case report form \[eCRF\]).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Ability to take concurrent aspirin daily (or enoxaparin subcutaneously daily), per published standard or institutional standard of care, as prophylactic anticoagulation.
• Note: For participants with prior history of deep vein thrombosis (DVT), low molecular weight heparin (LMWH) is mandatory.
• Left ventricular ejection fraction (LVEF) \>=50%.

You may not qualify if:

• Presence of non-secretory or oligo-secretory myeloma, smoldering MM, monoclonal gammopathy of undetermined significance, plasma-cell leukemia, Waldenstrom's macroglobulinemia, primary amyloidosis, or polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome.
• Central nervous system involvement by MM.
• Prior radiation therapy involving an estimated \>=25% of the hematopoietically active bone marrow. Radiotherapy should not be given within 14 days before enrollment. In case of palliative radiotherapy for pain control and if the involved field is small, 7 days will be considered a sufficient interval between the radiation treatment and administration of the study drugs.
• Treatment with any investigational products within 1 (one) year before the first dose of the study drug regimen.
• Presence of peripheral neuropathy of grade 1 with pain or grade 2 or higher.
• Previous or concurrent history of malignancies other than MM except for curatively treated cervical carcinoma in situ, non-melanoma skin cancer, superficial bladder cancer (Ta \[non-invasive tumor\], Tis \[carcinoma in situ\] and T1 \[tumor invades lamina propria\]), or localized prostate cancer.
• With evidence or history of bleeding diathesis. Any hemorrhage or bleeding event \>=common terminology criteria for adverse events (CTCAE) Grade 3 within 4 weeks of start of study medication.
• Major surgery within 14 days before randomization.
• Non-healing wound or ulcer.
• Seizure disorder requiring medication.
• Systemic treatment with strong cytochrome P-450 3A (CYP3A) inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort from Day-14 of cycle 1 until the safety follow-up.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study medication.

Sponsors & Collaborators

• Takeda: lead

Study Sites (6)

CEHON Centro de Hematologia e Oncologia da Bahia

Salvador, Estado de Bahia, 40110-090, Brazil

Location

Instituto COI de Educacao e Pesquisa

Rio de Janeiro, Rio de Janeiro, 22793-080, Brazil

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

Location

Universidade Estadual de Campinas UNICAMP - HEMOCENTRO

Campinas, São Paulo, 13083-878, Brazil

Location

Clinica Medica Sao Germano S/S Ltda.

São Paulo, São Paulo, 04537-080, Brazil

Location

Hospital das Clinicas da Faculdade de Medicina da USP

São Paulo, São Paulo, 05403-010, Brazil

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; Thalidomide; Dexamethasone

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2018
• First Posted: August 1, 2018
• Study Start: September 30, 2019
• Primary Completion: June 30, 2021
• Study Completion: May 31, 2023
• Last Updated: January 14, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share

Locations

BR (6)