Ibrutinib With or Without Bortezomib and Dexamethasone in Treating Patients With Relapsed or Refractory Immunoglobulin Light Chain Amyloidosis
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|ClinicalTrials.gov Identifier: NCT03130348|
Recruitment Status : Withdrawn (Study was dropped at site before participation)
First Posted : April 26, 2017
Last Update Posted : March 2, 2018
|Condition or disease||Intervention/treatment||Phase|
|Amyloidosis Immunoglobulin Light Chain Deposition||Drug: Bortezomib Drug: Dexamethasone Drug: Ibrutinib Other: Laboratory Biomarker Analysis||Phase 2|
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).
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.
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Ibrutinib With or Without Bortezomib and Dexamethasone for the Treatment of Patients With Relapsed/Refractory Immunoglobulin Light Chain Amyloidosis|
|Estimated Study Start Date :||March 15, 2018|
|Estimated Primary Completion Date :||April 2022|
|Estimated Study Completion Date :||April 2022|
Experimental: Treatment (ibrutinib, bortezomib, dexamethasone)
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.
Other: Laboratory Biomarker Analysis
- Overall hematologic response rate during the first 6 courses for patients treated with ibrutinib, bortezomib, and dexamethasone [ Time Frame: Up to 6 months ]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.
- Incidence of adverse events [ Time Frame: Up to 3 years ]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.
- Organ response rate [ Time Frame: Up to 3 years ]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.
- Overall hematologic response rate for single agent ibrutinib [ Time Frame: Up to 6 months ]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.
- Progression-free survival [ Time Frame: From registration to the earliest date of documentation of disease progression (on single agent or combination therapy) or death due to any cause, assessed up to 3 years ]Will be estimated using the method of Kaplan-Meier.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03130348
|Principal Investigator:||Taimur Sher||Mayo Clinic|