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Ixazomib Maintenance Study in Patients With AL Amyloidosis

Primary Purpose

AL Amyloidosis

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ixazomib
Dexamethasone
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for AL Amyloidosis focused on measuring Ixazomib, 18-069

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female patients 18 years or older.
  2. Biopsy-proven diagnosis of AL amyloidosis at the enrolling institution, according to the following standard criteria:

    • Histochemical diagnosis of amyloidosis, as based on tissue specimens with Congo red staining with exhibition of an apple-green birefringence
    • If clinical and laboratory parameters insufficient to establish AL amyloidosis or in cases of doubt, amyloid typing may be necessary
    • Measurable disease as defined by serum differential free light chain concentration (dFLC, difference between amyloid forming [involved] and non amyloid forming [uninvolved] free light chain [FLC]) ≥ 50 mg/L) (or M-protein of 0.5g/dl) prior to initial therapy.
    • At least one organ involved with AL amyloidosis including renal, cardiac, GI/Liver, peripheral/autonomic nervous system and/or soft tissue disease (Comenzo et al. Leukemia 2012).
  3. At least a hematologic partial response (PR) defined by the updated AL response criteria (Pallidini et al. JCO 2012) to one line of initial therapy (may include induction followed by autologous stem cell transplant (ASCT)).
  4. Patients must have >10% bone marrow plasma cells (on aspirate or biopsy) at initial diagnosis.
  5. At least 2 cycles of any induction therapy (that may include alkylators, corticosteroids, proteosome inhibitors, IMIDs - including in combination) or upfront ASCT (with or without preceding induction). Patients who receive ixazomib as part of initial therapy are eligible.
  6. Patients must be within 12 months of the start of initial therapy.
  7. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
  8. Female patients who:

    • Are postmenopausal for at least 1 year before the screening visit, OR
    • Are surgically sterile, OR
    • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND
    • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
    • Have a negative serum pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only
  9. Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:

    • Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
    • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
  10. Patients must meet the following clinical laboratory criteria:

    • Absolute neutrophil count (ANC) ≥ 1,000/mm^3
    • Platelet count ≥ 75,000/mm^3
    • Hemoglobin ≥ 8.0 g/dL
    • Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.
    • Total bilirubin ≤ 2 x the upper limit of the normal range (ULN) (except in patients with Gilbert"s syndrome who must have a total bilirubin of < 3 x ULN).
    • ALT/AST < 2.5x the upper limit of normal

Exclusion Criteria:

  1. Female patients who are lactating or have a positive serum pregnancy test during the screening period.
  2. Patients with primary refractory AL amyloidosis (< PR to initial therapy).
  3. Patients resistant and/or refractory to proteosome inhibitors.
  4. Active multiple myeloma with end organ damage (CRAB criteria).
  5. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure (NYHA class III/IV), unstable angina, or myocardial infarction within the past 6 months.
  6. Active systemic infection, including active hepatitis B or C virus infection. Patients who are human immunodeficiency virus (HIV) infected can be enrolled as long as CD4 is above 350, viral load has been undetectable for more than 6 months on stable anti-retroviral therapy, no previous AIDS-defining illness, and there is agreement with the HIV-treating physician that the patients can be monitored for possible treatment failure. Eligibility will be confirmed by the MSK Principal Investigator (PI).
  7. Any serious medical or psychiatric illness that could, in the investigator"s opinion, potentially interfere with the completion of treatment according to this protocol.
  8. Systemic treatment, within 14 days before the first dose of ixazomib with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John"s wort.
  9. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
  10. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing.
  11. Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with early stage prostate cancer, non melanoma skin cancer or carcinoma in situ of any type are not excluded; patients with malignancies that have undergone complete resection are not excluded.
  12. Patient has > Grade 2 peripheral neuropathy, or Grade 1 with pain (not controlled with medical therapy) on clinical examination during the screening period.
  13. Participation in other clinical trials, including those with other investigational agents not included in this trial, within 21 days of the start of this trial and throughout the duration of this trial.

Sites / Locations

  • Tufts Medical Center
  • Memorial Sloan Kettering Basking RidgeRecruiting
  • Memorial Sloan Kettering MonmouthRecruiting
  • Memorial Sloan Kettering BergenRecruiting
  • Memorial Sloan Kettering CommackRecruiting
  • Memorial Sloan Kettering WestchesterRecruiting
  • Memorial Sloan Kettering Cancer CenterRecruiting
  • Memorial Sloan Kettering NassauRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ixazomib

Arm Description

Enrolled patients will receive ixazomib at a fixed dose of 4mg on days 1, 8, and 15 of a 28-day cycle. Ixazomib will be given orally on days 1, 8, and 15 of a 28 day cycle. Dexamethasone 4mg-12mg will be allowed on days 1, 8, 15 if patients previously tolerated dexamethasone without issue. Treatment cycles will be repeated until disease progression for up to 24 cycles or until development of significant treatment-related toxicities.

Outcomes

Primary Outcome Measures

event free survival (EFS)
(EFS includes organ progression, next antiplasma cell directed therapy or death)

Secondary Outcome Measures

Full Information

First Posted
August 2, 2018
Last Updated
July 3, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Tufts Medical Center, Vanderbilt University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT03618537
Brief Title
Ixazomib Maintenance Study in Patients With AL Amyloidosis
Official Title
Ixazomib Maintenance Following Initial Therapy in Patients With Immunoglobulin Light Chain (AL) Amyloidosis
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 2, 2018 (Actual)
Primary Completion Date
August 2026 (Anticipated)
Study Completion Date
August 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Tufts Medical Center, Vanderbilt University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The purpose of this study is to learn if Ixazomib maintenance treatment (chemotherapy) works to control the disease. Through this study, the investigators hope to learn more about ways to prevent or delay relapse of AL Amyloidosis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AL Amyloidosis
Keywords
Ixazomib, 18-069

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
This is a Phase II open-label study.
Masking
None (Open Label)
Allocation
N/A
Enrollment
47 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ixazomib
Arm Type
Experimental
Arm Description
Enrolled patients will receive ixazomib at a fixed dose of 4mg on days 1, 8, and 15 of a 28-day cycle. Ixazomib will be given orally on days 1, 8, and 15 of a 28 day cycle. Dexamethasone 4mg-12mg will be allowed on days 1, 8, 15 if patients previously tolerated dexamethasone without issue. Treatment cycles will be repeated until disease progression for up to 24 cycles or until development of significant treatment-related toxicities.
Intervention Type
Drug
Intervention Name(s)
Ixazomib
Intervention Description
Ixazomib at a fixed dose of 4mg on days 1, 8, and 15 of a 28-day cycle. Ixazomib will be given orally on days 1, 8, and 15 of a 28 day cycle.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone 4mg-12mg will be allowed on days 1, 8, 15 if patients previously tolerated dexamethasone without issue.
Primary Outcome Measure Information:
Title
event free survival (EFS)
Description
(EFS includes organ progression, next antiplasma cell directed therapy or death)
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female patients 18 years or older. Biopsy-proven diagnosis of AL amyloidosis at the enrolling institution, according to the following standard criteria: Histochemical diagnosis of amyloidosis, as based on tissue specimens with Congo red staining with exhibition of an apple-green birefringence If clinical and laboratory parameters insufficient to establish AL amyloidosis or in cases of doubt, amyloid typing may be necessary Measurable disease as defined by serum differential free light chain concentration (dFLC, difference between amyloid forming [involved] and non amyloid forming [uninvolved] free light chain [FLC]) ≥ 50 mg/L) (or M-protein of 0.5g/dl) prior to initial therapy. At least one organ involved with AL amyloidosis including renal, cardiac, GI/Liver, peripheral/autonomic nervous system and/or soft tissue disease (Comenzo et al. Leukemia 2012). At least a hematologic partial response (PR) defined by the updated AL response criteria (Pallidini et al. JCO 2012) to one line of initial therapy (may include induction followed by autologous stem cell transplant (ASCT)). Patients must have >10% bone marrow plasma cells (on aspirate or biopsy) at initial diagnosis. At least 2 cycles of any induction therapy (that may include alkylators, corticosteroids, proteosome inhibitors, IMIDs - including in combination) or upfront ASCT (with or without preceding induction). Patients who receive ixazomib as part of initial therapy are eligible. Patients must be within 12 months of the start of initial therapy. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. Female patients who: Are postmenopausal for at least 1 year before the screening visit, OR Are surgically sterile, OR If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) Have a negative serum pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following: Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) Patients must meet the following clinical laboratory criteria: Absolute neutrophil count (ANC) ≥ 1,000/mm^3 Platelet count ≥ 75,000/mm^3 Hemoglobin ≥ 8.0 g/dL Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. Total bilirubin ≤ 2 x the upper limit of the normal range (ULN) (except in patients with Gilbert"s syndrome who must have a total bilirubin of < 3 x ULN). ALT/AST < 2.5x the upper limit of normal Exclusion Criteria: Female patients who are lactating or have a positive serum pregnancy test during the screening period. Patients with primary refractory AL amyloidosis (< PR to initial therapy). Patients resistant and/or refractory to proteosome inhibitors. Active multiple myeloma with end organ damage (CRAB criteria). Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure (NYHA class III/IV), unstable angina, or myocardial infarction within the past 6 months. Active systemic infection, including active hepatitis B or C virus infection. Patients who are human immunodeficiency virus (HIV) infected can be enrolled as long as CD4 is above 350, viral load has been undetectable for more than 6 months on stable anti-retroviral therapy, no previous AIDS-defining illness, and there is agreement with the HIV-treating physician that the patients can be monitored for possible treatment failure. Eligibility will be confirmed by the MSK Principal Investigator (PI). Any serious medical or psychiatric illness that could, in the investigator"s opinion, potentially interfere with the completion of treatment according to this protocol. Systemic treatment, within 14 days before the first dose of ixazomib with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John"s wort. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing. Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with early stage prostate cancer, non melanoma skin cancer or carcinoma in situ of any type are not excluded; patients with malignancies that have undergone complete resection are not excluded. Patient has > Grade 2 peripheral neuropathy, or Grade 1 with pain (not controlled with medical therapy) on clinical examination during the screening period. Participation in other clinical trials, including those with other investigational agents not included in this trial, within 21 days of the start of this trial and throughout the duration of this trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Heather Landau, MD
Phone
212-639-8808
Email
ABMTTrials@mskcc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Hani Hassoun, MD
Phone
212-639-3228
Email
ABMTTrials@mskcc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heather Landau, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Memorial Sloan Kettering Basking Ridge
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heather Landau, MD
Phone
212-639-8808
Facility Name
Memorial Sloan Kettering Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heather Landau, MD
Phone
212-639-8808
Facility Name
Memorial Sloan Kettering Bergen
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heather Landau, MD
Phone
212-639-8808
Facility Name
Memorial Sloan Kettering Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heather Landau, MD
Phone
212-639-8808
Facility Name
Memorial Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heather Landau, MD
Phone
212-639-8808
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heather Landau, MD
Phone
212-639-8808
First Name & Middle Initial & Last Name & Degree
Hani Hassoun, MD
Phone
212-639-3228
First Name & Middle Initial & Last Name & Degree
Heather Landau, MD
Facility Name
Memorial Sloan Kettering Nassau
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heather Landau, MD
Phone
212-639-8808

12. IPD Sharing Statement

Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

Ixazomib Maintenance Study in Patients With AL Amyloidosis

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