NCT03130348

Ibrutinib With or Without Bortezomib and Dexamethasone in Treating Patients With Relapsed or Refractory Immunoglobulin Light Chain Amyloidosis

Phase II Study of Ibrutinib With or Without Bortezomib and Dexamethasone for the Treatment of Patients With Relapsed/Refractory Immunoglobulin Light Chain Amyloidosis

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well ibrutinib with or without bortezomib and dexamethasone works in treating patients with immunoglobulin light chain amyloidosis that has come back after a period of improvement or that does not respond to treatment. Ibrutinib and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ibrutinib with or without bortezomib and dexamethasone may work better in treating patients with relapsed or refractory immunoglobulin light chain amyloidosis.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the overall hematologic response rate (stringent complete response \[sCR\] + amyloid complete response \[ACR\]+ very good partial response \[VGPR\] + partial response \[PR\]) during the first 6 cycles for ibrutinib with bortezomib and dexamethasone added for lack of response in patients with amyloid light chain (AL). SECONDARY OBJECTIVES: I. To evaluate overall hematologic response rate (sCR+ACR+VGPR+PR) of single agent ibrutinib in patients with AL. II. To evaluate overall hematologic response rate (sCR+ACR+VGPR+PR) to ibrutinib + bortezomib and dexamethasone (Vd) in subjects with progressive disease after initial response to single agent ibrutinib. III. To describe the toxicities associated with ibrutinib, alone and in combination with Vd, in patients with AL. IV. To determine the organ response in AL patients treated with ibrutinib alone and in combination with Vd. V. To determine 3 year progression free survival of AL patients on the study. TERTIARY OBJECTIVES: I. To characterize health related quality of life of patients. II. To determine the caregiver and patient disease burden. III. To determine the correlation between cardiac biomarkers and hematologic response to therapy. IV. To evaluate the effect of ibrutinib on AL microenvironment. V. To characterize BTK expression in neoplastic plasma cells. VI. To evaluate the characterization of CD38 expression on neoplastic plasma cells. OUTLINE: Patients receive ibrutinib orally (PO) daily (QD) on days 1-28. After 3 courses, patients who achieve partial response repeat treatment every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Patients who do not achieve partial response after 3 courses continue receiving ibrutinib PO QD on days 1-28. Beginning at course 4, patients who do not achieve partial response also receive bortezomib subcutaneously (SC) and dexamethasone PO on days 1, 8, and 15. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, and then every 6 months for 2 years.

Conditions

• Amyloidosis
• Immunoglobulin Light Chain Deposition

Interventions

Type	Name	Description
DRUG	Bortezomib	Given SC
DRUG	Dexamethasone	Given PO
DRUG	Ibrutinib	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies

Timeline

• Start date: 2018-03-15
• Primary completion: 2022-04-01
• Completion: 2022-04-01
• First posted: 2017-04-26
• Last updated: 2018-03-02

Regulatory

• FDA-regulated drug study