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NCT Number: NCT01645930

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

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Pokfulam, Hong Kong

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About this study

The drug being tested in this study was ixazomib. Ixazomib was tested to treat adult Asian people who had relapsed and/or refractory multiple myeloma.

The study enrolled 43 patients. Participants were enrolled to receive:

  • Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg.

All participants were asked to take ixazomib capsules orally on Days 1, 8, and 15; lenalidomide capsules, orally, on Days 1 through 21; and dexamethasone tablets, orally, on Days 1, 8, 15, and 22 of a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity (up to 20 cycles).

This multi-center trial was conducted in Singapore, Hong Kong and South Korea. The overall time to participate in this study was up to 577 days. Participants made multiple visits to the clinic, and were contacted 30 days after last dose of study drug for a follow-up assessment.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

Ixazomib

Drug

Ixazomib capsules

Lenalidomide

Drug

Lenalidomide capsules

Dexamethasone

Drug

Dexamethasone tablets

Primary outcomes

  1. Cmax: Maximum Observed Plasma Concentration for Ixazomib

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

  2. Cmax: Maximum Observed Plasma Concentration for Ixazomib

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

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

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

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

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

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

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

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

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

  7. Number of Participants With Dose Limiting Toxicities (DLTs)

    Time frame: Cycle 1 (up to Day 28)

    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.

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

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

    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.

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

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

    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.

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

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

    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.

Secondary outcomes

  1. Percentage of Participants With Confirmed Best Response Category

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

    Percentage of participants who achieve or maintain any best response category during the treatment period were reported. Best response includes complete response (CR), very good partial response (VGPR), and partial response (PR). Response was assessed according to IMWG criteria. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow; PR: ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour.

  2. Duration of Response (DOR)

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

    DOR was defined as the length of time between the date of first documented response (PR, VGPR, or CR) and the date of first documented progressive disease (PD). According to IMWG criteria: CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow; PR: ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour.

Sponsors and collaborators

Lead sponsor

Millennium Pharmaceuticals, Inc.

Industry

Registry information

Official study title

A Phase 1 Pharmacokinetic and Tolerability Study of Oral MLN9708 Plus Lenalidomide and Dexamethasone in Adult Asian Patients With Relapsed and/or Refractory Multiple Myeloma

Important dates

Study start
2012
Primary completion
2014
Study completion
2017
First posted
Jul 20, 2012
Registry last updated
Nov 8, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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