Study of Oral Ixazomib in Adult Participants With Relapsed and/or Refractory (RR) Multiple Myeloma

Millennium Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Relapsed and Refractory Multiple Myeloma

Treatments: Drug: Ixazomib

Study type: Interventional

Funder types: Industry

Identifiers

NCT00932698

U1111-1177-7936 (Registry Identifier)

C16003

Details and patient eligibility

About

This study will determine the safety profile, tolerability, and maximum tolerated dose (MTD) and disease response of Ixazomib administered orally in participants with relapsed and/or refractory multiple myeloma.

Full description

The drug being tested in this study is ixazomib. Ixazomib is being tested to treat people who have multiple myeloma. This study will look at the safety and efficacy of ixazomib and will enroll approximately 60 participants.

Participants will receive ixazomib by oral capsule twice weekly on Days 1, 4, 8, and 11 of a 21-day cycle. The study will consist of a dose escalation phase to determine the MTD, followed by an expansion phase in which participants will be treated at the MTD.

This multi-center trial will be conducted in the United States. The overall time to participate in this study is 8 years.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Each participant must meet all of the following inclusion criteria to be enrolled in the study:

• Multiple myeloma diagnosed according to the standard criteria.
• Participants with multiple myeloma who have relapsed following at least 2 lines of therapy.
• Participants must have measurable disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
• Male participants who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse.
• Voluntary written consent.
• Suitable venous access for study-required blood sampling.

Exclusion criteria

Participants meeting any of the following exclusion criteria are not to be enrolled in the study:

• Peripheral neuropathy greater than or equal to (>=) Grade 2.
• Female participants who are lactating or have a positive serum pregnancy test during the screening period.
• Major surgery within 14 days before the first dose of study drug.
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study treatment.
• Life-threatening illness unrelated to cancer.
• Diarrhea > Grade 1, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) categorization.
• Systemic antineoplastic or radiation therapy within 14 days of cytotoxic agents within 21 days before the first dose of study treatment.
• Treatment with any investigational products within 21 days before the first dose of study treatment.
• Treatment with any investigational proteasome inhibitor.
• Systemic treatment with prohibited medication.
• Ongoing therapy with corticosteroids greater than 10mg of prednisone or its equivalent per day. Inhaled and topical steroids are permitted.
• Central nervous system involvement.
• Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months.
• Corrected QT interval (QTc) > 470 milliseconds on a 12-lead electrocardiogram (ECG) obtained during the screening period.
• Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol.
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption of tolerance of ixazomib including difficulty swallowing.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 11 patient groups

Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2

Experimental group

Description:

Ixazomib 0.24 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days).

Treatment:

Drug: Ixazomib

Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2

Experimental group

Description:

Ixazomib 0.48 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days).

Treatment:

Drug: Ixazomib

Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2

Experimental group

Description:

Ixazomib 0.8 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days).

Treatment:

Drug: Ixazomib

Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2

Experimental group

Description:

Ixazomib 1.2 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days).

Treatment:

Drug: Ixazomib

Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2

Experimental group

Description:

Ixazomib 1.68 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days).

Treatment:

Drug: Ixazomib

Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2

Experimental group

Description:

Ixazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days).

Treatment:

Drug: Ixazomib

Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2

Experimental group

Description:

Ixazomib 2.23 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days).

Treatment:

Drug: Ixazomib

Relapsed and Refractory Expansion Cohort: Ixazomib 2 mg/m^2

Experimental group

Description:

Ixazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days).

Treatment:

Drug: Ixazomib

Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2

Experimental group

Description:

Ixazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after \>=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days).

Treatment:

Drug: Ixazomib

Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2

Experimental group

Description:

Ixazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after \>=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor (Up to 550 days).

Treatment:

Drug: Ixazomib

Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2

Experimental group

Description:

Ixazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days).

Treatment:

Drug: Ixazomib