Ixazomib In Combination With Cyclophosphamide And Dexamethasone for Newly Diagnosed AL Amyloidosis
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|ClinicalTrials.gov Identifier: NCT03236792|
Recruitment Status : Recruiting
First Posted : August 2, 2017
Last Update Posted : January 11, 2019
Light chain (AL) amyloidosis is a bone marrow disorder that affects a wide range of organs that can lead to organ dysfunction and death. Amyloid is an abnormal protein that is produced in your bone marrow and cannot be broken down. It builds up in different organs preventing them from working well. The most commonly affected organs are the kidneys, heart, liver, spleen, nervous system, and digestive tract. Treatment with chemotherapy can stop the growth of abnormal cells that produce this abnormal protein. Decrease in amyloid protein in the body improves the function of the affected organs.
The primary purpose of this study is to determine the safest dose of the medications and how well you tolerate them or the "maximum tolerated dose" (MTD). The study uses Ixazomib in combination with cyclophosphamide and dexamethasone to treat people with newly diagnosed AL amyloidosis. This combination of medications is an oral regimen that is taken over 6 cycles. The first part of study will determine the safety of this regimen and the second part of the study will determine how effective this combination of drugs is to treat your disease.
|Condition or disease||Intervention/treatment||Phase|
|AL Amyloidosis||Drug: Ixazomib Drug: Cyclophosphamide Drug: Dexamethasone||Phase 1 Phase 2|
This study is a phase 1/2 study to assess safety and hematologic response rate of Ixazomib (MLN) in combination with Cyclophosphamide (CTX) and Dexamethasone (DEX). This is an open label multi-center, dose escalation safety study for patients with newly diagnosed AL Amyloidosis.
A 3+3 design will be utilized to determine the MTD for MLN + CTX + DEX in 28-day treatment cycle. Treatment cycles will be repeated up to 6 cycles or until disease progression or until development of significant treatment-related toxicities. A total of up to 30 patients are planned to enroll into the study, with a maximum of 18 patients in the dose escalation arm and 18 patients in the MTD expansion arm. The cohort of 6 patients treated at the MTD during the dose expansion phase will also serve as the initial 6 patients for the expansion Phase II cohort. These 6 patients will contribute data to both the phase I dose escalation study and the phase II expansion study. To complete the Phase II cohort, an additional 12 new patients will need to be enrolled.
MLN will be taken orally on days 1, 8, and 15 at doses of 3 mg or 4 mg. CTX will be taken orally on the same days with dose escalation from 300 mg up to 500 mg. DEX will be taken orally on days 1, 8, 15, 22 at 20 mg in the 28-day cycle.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1/2 Study Of Ixazomib In Combination With Cyclophosphamide And Dexamethasone In Patients With Newly Diagnosed Immunoglobulin Light Chain AL Amyloidosis|
|Actual Study Start Date :||June 12, 2017|
|Estimated Primary Completion Date :||June 2020|
|Estimated Study Completion Date :||June 2020|
Experimental: Newly Diagnosed AL Amyloidosis
Ixazomib/Cyclophosphamide/Dexamethasone. Treatment cycles will be repeated up to 6 cycles or until disease progression or until development of significant treatment-related toxicities.
3 mg or 4mg of Ixazomib will be taken orally on days 1, 8, and 15 of a 28-day cycle
300, 400, or 500 mg of oral Cyclophosphamide on days 1, 8, and 15 of a 28-day cycle
20 mg of oral Dexamethasone on days 1, 8, 15, 22 in a 28-day cycle
- Maximum Tolerated Dose (MTD) [ Time Frame: up to 3 years ]The MTD of ixazomib given in combination with cyclophosphamide and dexamethasone, 3 + 3 design in Phase 1 of this study
- Response Rate [ Time Frame: up to 3 years ]The incidence of hematologic response rate as defined by complete response (CR), very good partial response (VGPR), partial response (PR), and stable disease (SD)
- Frequency of organ response [ Time Frame: up to 3 years ]The frequency of organ response as per the ISA criteria: Cardiac response and progression -NT-proBNP response (>30% and > 300 ng/L decrease if baseline NT-proBNP 650 ng/L). NT-proBNP progression (>30% and >300 ng/L increase). cTn progression (>33% increase). NYHA class response (> two-class decrease if baseline NYHA class 3 or 4). EF progression (>10% decrease). Renal response and progression - Renal response: >30% decrease in proteinuria or drop of proteinuria below 0.5 g/24 h in the absence of renal progression. Renal progression: >25% decrease in eGFR. Liver response criteria- include a 50% decrease in abnormal alkaline phosphatase value and decrease in liver size of at least 2cm.
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): NCT03236792
|Contact: Keren Osman, MDemail@example.com|
|Contact: Sonia Rai, MD,MHAfirstname.lastname@example.org|
|United States, New York|
|Icahn School of Medicine at Mount Sinai||Recruiting|
|New York, New York, United States, 10029|
|Contact: Keren Osman, MD|
|Contact: Sonia Rai, MHA,MD 212-241-6021 email@example.com|
|Principal Investigator: Keren Osman, MD|
|Columbia University Medical Center||Withdrawn|
|New York, New York, United States, 10032|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Heather Landau, MD|
|Contact: Beth Hoover HooverE@mskcc.org|
|Principal Investigator: Heather Landau, MD|
|Weill Cornell Medicine||Not yet recruiting|
|New York, New York, United States, 10065|
|Contact: Sheetal Ramnath firstname.lastname@example.org|
|Principal Investigator: Cara Rosenblaum, MD|
|Principal Investigator:||Keren Osman, MD||Icahn School of Medicine at Mount Sinai|