Phase 1 Pharmacokinetic Study of Oral Ixazomib Plus Lenalidomide and Dexamethasone in Adult Asian Participants With Relapsed and/or Refractory Multiple Myeloma

NCT01645930 | Completed Phase 1 Results

• 3 other identifiers: C16013U1111-1155-5943HKUCTR-1593
• Study Type: interventional
• Target: 43
• Locations: 3 countries
• Sites: 5

Brief Summary

The purpose of this Phase 1 study is to characterize the pharmacokinetic (PK) and tolerability of oral ixazomib (MLN9708) when administered in combination with lenalidomide and dexamethasone in adult Asian participants with relapsed and/or refractory multiple myeloma.

Conditions

Multiple Myeloma

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (10)

• Cmax: Maximum Observed Plasma Concentration for Ixazomib

  Cycle 1, Day 1 pre-dose and multiple time-points (up to 168 hours) post-dose

• Cmax: Maximum Observed Plasma Concentration for Ixazomib

  Cycle 1, Day 15 pre-dose and multiple time-points (up to 336 hours) post-dose

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib

  Cycle 1, Day 1 pre-dose and multiple time-points (up to 168 hours) post-dose

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib

  Cycle 1, Day 15 pre-dose and multiple time-points (up to 336 hours) post-dose

• AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Ixazomib

  Cycle 1, Day 1 pre-dose and multiple time-points (up to 168 hours) post-dose

• AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Ixazomib

  Cycle 1, Day 15 pre-dose and multiple time-points (up to 336 hours) post-dose

• Number of Participants With Dose Limiting Toxicities (DLTs)

  DLT was defined as any of the following AEs that were considered by investigator to be possibly related to therapy: 1. Grade 4 neutropenia lasting at least 7 consecutive days; 2. Grade 3 neutropenia with fever and/or infection; 3. Grade 4 thrombocytopenia at least 7 consecutive days; 4. Grade 3 thrombocytopenia with clinically significant bleeding; 5. Platelet count \<10,000/mm\^3; 6. Grade 2 peripheral neuropathy with pain or ≥Grade 3 peripheral neuropathy; 7. Grade 3 or greater nausea and / or emesis despite the use of optimal anti-emetic prophylaxis; 8. Grade 3 or greater diarrhea that occurred despite maximal supportive therapy; 9. Any other Grade 3 or greater nonhematologic toxicity with the following exceptions: Grade 3 arthralgia/myalgia, \<1 week Grade 3 fatigue; 10. A delay of \>2 weeks in the subsequent cycle of treatment; 11. Other combination study drug-related nonhematologic toxicities ≥Grade 2 that, in the opinion of the investigator, required discontinuation of study drug.

  Cycle 1 (up to Day 28)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or was a medically important event.

  From the first dose of study drug through 30 days after the last dose of study drug (up to 577 days)

• Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Adverse Events of ≥Grade 3 Intensity

  Clinically significant laboratory abnormalities were defined as any test results which were observed beyond the clinically acceptable limits as per the discretion of investigator. Clinical laboratory tests included chemistry, hematology and urinalysis tests.

  From the first dose of study drug through 30 days after the last dose of study drug (up to 577 days)

• Number of Participants With Clinically Significant Vital Signs Reported as Adverse Events

  The number of participants who meet markedly abnormal criteria for vital signs, included diastolic and systolic blood pressure, heart rate, oral temperature, respiratory rate, and body weight.

  From the first dose of study drug through 30 days after the last dose of study drug (up to 577 days)

Secondary Outcomes (2)

• Percentage of Participants With Confirmed Best Response Category

  From Cycle 1, Day 1 to Cycle 3, Day 1 until disease progression (approximately 20 months)

• Duration of Response (DOR)

  From date of documentation of a confirmed response to date of progressive disease, (approximately 20 months)

Study Arms (1)

Ixazomib+Lenalidomide+Dexamethasone

EXPERIMENTAL

Ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15; lenalidomide 25 mg, capsules, orally, once on Days 1 through 21; and dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15, and 22 of a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity (up to 20 cycles)

Drug: Ixazomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Ixazomib DRUG

Ixazomib capsules

Ixazomib+Lenalidomide+Dexamethasone

Lenalidomide DRUG

Lenalidomide capsules

Ixazomib+Lenalidomide+Dexamethasone

Dexamethasone DRUG

Dexamethasone tablets

Ixazomib+Lenalidomide+Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Male or female East Asian participants 18 years or older
• Diagnosed Multiple Myeloma according to standard criteria
• Measurable disease as specified in study protocol
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Participants with relapsed and/or refractory Multiple Myeloma who have received 1 to 3 prior therapies
• Meet the clinical laboratories criteria as specified in the protocol
• Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse; must also adhere to the guidelines of the lenalidomide pregnancy prevention program
• Male participants who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse and must adhere to the guidelines of the lenalidomide pregnancy prevention program
• Must be able to take concurrent aspirin 325 mg daily
• Voluntary written consent

You may not qualify if:

• Female participants who are lactating or pregnant
• Major surgery or radiotherapy within 14 days before enrollment
• Infection requiring systematic antibiotics within 14 days before study enrollment
• Central nervous system involvement
• Failure to have fully recovered from the effects of prior chemotherapy regardless of the interval since last treatment
• Systemic treatment with strong inhibitors of cytochrome P450 1A2 (CYP1A2), strong inhibitors of CYP3A, or strong CYP3A inducers, or use of Ginko biloba or St. John's wort within 14 days before study enrollment
• Diagnosis of Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome
• Evidence of current uncontrolled cardiovascular conditions
• Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol
• Known allergy to any of the study medications
• Known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of ixazomib
• Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease with the exception of nonmelanoma skin cancer or any completely resected carcinoma in situ
• Ongoing or active systemic infection, active hepatitis B virus infect, active hepatitis C infection, or known human immunodeficiency virus (HIV) positive

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (5)

Unknown Facility

Pokfulam, Hong Kong

Location

Unknown Facility

Shatin, Hong Kong

Location

Unknown Facility

Singapore, Singapore

Location

Unknown Facility

Incheon, South Korea

Location

Unknown Facility

Seoul, South Korea

Location

Related Publications (1)

• Gupta N, Goh YT, Min CK, Lee JH, Kim K, Wong RS, Chim CS, Hanley MJ, Yang H, Venkatakrishnan K, Hui AM, Esseltine DL, Chng WJ. Pharmacokinetics and safety of ixazomib plus lenalidomide-dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study. J Hematol Oncol. 2015 Sep 4;8:103. doi: 10.1186/s13045-015-0198-1.

  PMID: 26337806 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; Lenalidomide; 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

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2012
• First Posted: July 20, 2012
• Study Start: December 17, 2012
• Primary Completion: July 14, 2014
• Study Completion: April 11, 2017
• Last Updated: November 8, 2018
• Results First Posted: November 8, 2018

Record last verified: 2018-03

Locations

SG (1); KR (2); HK (2)