Nutritional and Metabolic Diseases

All Conditions

Neoplasms

Immune System Diseases

Blood and Lymph Conditions

Rare Diseases

Amyloidosis

Immunoglobulin Light-chain Amyloidosis

Proteostasis Deficiencies

Metabolic Diseases

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Immunoproliferative Disorders

Paraproteinemias

AL Amyloidosis

All Drugs and Chemicals

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Dermatologic Agents

Anti-Infective Agents

Amino Acids

Antibodies

Dexamethasone

Bortezomib

Dexamethasone acetate

BB 1101

Immunoglobulins

Immunoglobulins, Intravenous

Ibrutinib

Ichthammol

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Patients receive ibrutinib PO 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 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.

Laboratory Biomarker Analysis

Taimur Sher

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.

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.

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

Will include a confirmed stringent complete response, amyloid complete response, very good partial response, and partial response. Confirmation will be defined as a response that is maintained on two consecutive evaluations at least 2 weeks apart. Progression will be defined as either hematologic or organ progression. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Adverse events will be summarized separately for single agent Ibrutinib and combination therapy.

Will be estimated by the total number of patients who have an organ response divided by the total number of evaluable patients who had involvement in that organ at baseline. Exact binomial 95% confidence intervals for the true organ Up to response rate will be calculated.

Will be estimated by the total number of patients who achieve a partial response, very good partial response, stringent complete response, or amyloid complete response while receiving single agent ibrutinib divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall hematologic response rate will be calculated.

Will be estimated using the method of Kaplan-Meier.

National Cancer Institute (NCI)

Mayo Clinic

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Ibrutinib With or Without Bortezomib and Dexamethasone in Treating Patients With Relapsed or Refractory Immunoglobulin Light Chain Amyloidosis	NCT03130348	Amyloidosis Immunoglobulin ...	Bortezomib Dexamethasone Ibrutinib Laboratory Biom...	18 Years -	Mayo Clinic
Ibrutinib With or Without Bortezomib and Dexamethasone in Treating Patients With Relapsed or Refractory Immunoglobulin Light Chain Amyloidosis	NCT03130348	Amyloidosis Immunoglobulin ...	Bortezomib Dexamethasone Ibrutinib Laboratory Biom...	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for immunoglobulin light chain deposition