Study of Oral Ixazomib in Adult Participants With Relapsed or Refractory Light Chain Amyloidosis

Millennium Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Light-Chain Amyloidosis

Treatments: Drug: Dexamethasone; Drug: Ixazomib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01318902

2010-022497-13 (EudraCT Number)

U1111-1168-1192 (Registry Identifier)

C16007

Details and patient eligibility

About

This study will include participants with previously treated systemic relapsed or refractory light-chain (AL) amyloidosis who require further therapy and will be aimed at determining the safety profile and the maximum tolerated dose/recommended phase 2 dose of MLN9078 (Ixazomib) administered orally.

Enrollment: 27 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Male or female participants 18 years or older
• Biopsy-proven systemic relapsed or refractory light-chain (AL) amyloidosis, which after at least 1 prior therapy, in the investigator's opinion, requires further treatment
• If received stem cell transplant, must be at least 3 months posttransplantation and recovered from side effects
• Must have measurable disease defined as serum differential free light chain concentration ≥ 40 mg/L
• Must have objective measurable organ (heart or kidney) amyloid involvement
• Must have cardiac biomarker risk stage I or II disease
• Must have adequate hematologic, hepatic, and renal function
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Female participants who are postmenopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse
• Male participants who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse
• Voluntary written consent

Exclusion Criteria

• Peripheral neuropathy that is greater or equal to Grade 2
• Cardiac status as described in protocol
• Severe diarrhea (≥ Grade 3) not controllable with medication or requires administration of total parenteral nutrition
• Known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of MLN9708
• Uncontrolled infection requiring systematic antibiotics
• Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
• Presence of other active malignancy with the exception of nonmelanoma skin cancer, cervical cancer, treated early-stage prostate cancer provided that prostate-specific antigen is within normal limit, or any completely resected carcinoma in situ
• Female participants who are lactating or pregnant
• Major surgery within 14 days before the first dose of study drug
• Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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27 participants in 4 patient groups

Dose Escalation Cohort: Ixazomib 4.0 mg

Experimental group

Description:

Ixazomib 4.0 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.

Treatment:

Drug: Dexamethasone

Drug: Ixazomib

Dose Escalation Cohort: Ixazomib 5.5 mg

Experimental group

Description:

Ixazomib 5.5 mg, capsule, orally, once weekly on Days 1, 8 and 15 during each 28-day treatment cycle for 3 cycles. If there was no hematologic response, dexamethasone 40 mg, tablet, orally was added once on Days 1 to 4 of every cycle, beginning in Cycle 4 for 3 additional cycles. If there was no hematologic response the participant was discontinued. Participants with hematologic response continued treatment up to maximum 12 cycles.

Treatment:

Drug: Dexamethasone

Drug: Ixazomib

Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)

Experimental group

Description:

Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were not treated with any other proteasome inhibitor (PI). Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.

Treatment:

Drug: Ixazomib

Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)

Experimental group

Description:

Ixazomib 4.0 mg, capsule, orally, on Days 1, 8 and 15 during a 28-day treatment cycle until PD or unacceptable toxicity, for participants with relapsed or refractory amyloidosis and who were previously treated with any other PI. Duration of treatment was up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months.

Treatment:

Drug: Ixazomib