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

NCT ID: NCT01318902

Last Updated: 2020-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-27
• Study Completion Date: 2018-11-13

Brief Summary

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.

Conditions

Light-Chain Amyloidosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Escalation Cohort: Ixazomib 4.0 mg

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.

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules.

Dexamethasone

Intervention Type: DRUG

Dexamethasone tablets.

Dose Escalation Cohort: Ixazomib 5.5 mg

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.

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules.

Dexamethasone

Intervention Type: DRUG

Dexamethasone tablets.

Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)

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.

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules.

Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)

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.

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules.

Interventions

Ixazomib

Ixazomib capsules.

Intervention Type: DRUG

Dexamethasone

Dexamethasone tablets.

Intervention Type: DRUG

Other Intervention Names

MLN9708

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Tufts Medical Center

Boston, Massachusetts, United States

Boston Medical Center

Boston, Massachusetts, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Mount Sinai Medical Center

New York, New York, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

University Health Network

Toronto, Ontario, Canada

CHU Limoges, Department of Hematology and Cell Therapy, Reference Center for AL amyloidosis

Limoges, , France

Universitatsklinikum Heidelberg Innere Medizin V; Hamatologie, Onkologie und Rheumatologie

Heidelberg, , Germany

Amyloidosis Research & Treatment Center, Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Countries

United States; Canada; France; Germany; Italy

References

Sanchorawala V, Comenzo R, Zonder J, Kukreti V, Cohen A, Dispenzieri A, et al. MLN9708, an investigational oral proteasome inhibitor (PI), in relapsed or refractory lightchain (AL) amyloidosis. Clinical Lymphoma Myeloma and Leukemia 2013;13(suppl 1):S153-4; abstr P-229.

Reference Type: RESULT

Sanchorawala V, Zonder J, Comenzo R, Schönland S, Dispenzieri A, Berg D, et al. Poster Presentation: Phase 1 study of MLN9708, a novel, investigational oral proteasome inhibitor, in patients with relapsed or refractory light-chain amyloidosis. XIII International Symposium on Amyloidosis, Groningen, The Netherlands 2012.

Reference Type: RESULT

Merlini G, Sanchorawala V, Zonder J, Kukreti V, Schonland S, Jaccard A, et al. MLN9708, a novel, investigational oral proteasome inhibitor, in patients with relapsed or refractory light-chain amyloidosis (AL): results of a phase 1 study. In: 54th ASH Annual Meeting and Exposition; 2012 8-11 December; Atlanta, GA; p. abstr 731.

Reference Type: RESULT

Sanchorawala V, Palladini G, Kukreti V, Zonder JA, Cohen AD, Seldin DC, Dispenzieri A, Jaccard A, Schonland SO, Berg D, Yang H, Gupta N, Hui AM, Comenzo RL, Merlini G. A phase 1/2 study of the oral proteasome inhibitor ixazomib in relapsed or refractory AL amyloidosis. Blood. 2017 Aug 3;130(5):597-605. doi: 10.1182/blood-2017-03-771220. Epub 2017 May 26.

Reference Type: DERIVED

PMID: 28550039 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

2010-022497-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1168-1192

Identifier Type: REGISTRY

Identifier Source: secondary_id

C16007

Identifier Type: -

Identifier Source: org_study_id