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Idelalisib for Immunoglobulin M (IgM)-Associated Primary (AL) Amyloidosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02590588
Recruitment Status : Terminated (Poor accrual)
First Posted : October 29, 2015
Results First Posted : May 10, 2017
Last Update Posted : September 21, 2017
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
John Mark Sloan, Boston Medical Center

Brief Summary:
The investigators expect to enroll 15 participants with relapsed or refractory IgM-associated AL amyloidosis onto this Phase II clinical trial. Idelalisib will be self-administered orally at a dose of 100 mg twice daily (may be increased to 150 mg (one tablet) twice daily after 3 months at investigator discretion). Participants will be treated until disease progression, unacceptable toxicity, or decision to withdraw from the trial. Disease evaluations will be performed every three months until disease progression.

Condition or disease Intervention/treatment Phase
Amyloidosis Drug: Idelalisib Phase 2

Detailed Description:

This study includes the use of Idelalisib to treat previously treated patients with IgM-associated AL Amyloidosis at Boston Medical Center. Boston Medical Center is internationally recognized as a leader in amyloidosis research and patient care through the activities of the multidisciplinary Amyloid Center at Boston University. The problematic cell in most forms of AL amyloidosis shares similarities with multiple myeloma. However, in the small subset of AL Amyloidosis patients with an IgM paraprotein, the cells are more typically related to lymphoplasmacytic lymphoma or Waldenstrom's macroglobulinemia. Because clonal cluster of differentiation antigen 20 (CD20)+ lymphoplasmacytic cells are usually responsible for IgM paraproteins, treatment paradigms based on Waldenstrom's macroglobulinemia (WM) may be more appropriate than myeloma-based strategies. Idelalisib has been shown to be active and well tolerated in patients with relapsed/refractory non-Hodgkin lymphoma including chronic lymphocytic lymphoma, and lymphoplasmacytic lymphoma with or without Waldenström's macroglobulinemia (WM). The side effect profile of idelalisib merges well with the known predisposition to toxicity of amyloidosis patient.

The investigators expect to enroll 15 participants with IgM-associated AL amyloidosis onto this Phase II clinical trial. Idelalisib will be self-administered orally at a dose of 100 mg (1 tablet) twice daily (may be escalated to 150 mg (one tablet) twice daily after 3 months at investigator discretion). Participants will be treated until disease progression, unacceptable toxicity, or decision to withdraw from the trial. Disease evaluations will be performed every three months until disease progression.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study of Phosphatidylinositol-3-kinase (PI3K) Inhibitor, Idelalisib (GS-1101), in IgM-Associated AL Amyloid
Actual Study Start Date : January 2016
Actual Primary Completion Date : March 27, 2017
Actual Study Completion Date : March 27, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Amyloidosis
Drug Information available for: Idelalisib

Arm Intervention/treatment
Experimental: Idelalisib
Idelalisib 100 mg twice daily with possible escalation after 3 months to 150 mg twice daily at investigator discretion.
Drug: Idelalisib
Idelalisib daily until unacceptable toxicity or disease progression.
Other Name: GS-1101




Primary Outcome Measures :
  1. Overall Response [ Time Frame: 3 months ]
    Evaluate hematologic response according to standard criteria


Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 1 year ]
    Evaluate time to progression

  2. Organ Response [ Time Frame: 3 months ]
    Number of patients with organ response using standard AL amyloidosis criteria.

  3. Evaluate Safety and Tolerability of Agent [ Time Frame: 3 months ]
    Number of Participants With Treatment-Related Adverse Events as Assessed by Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0

  4. Quality of Life [ Time Frame: 3 months ]
    Evaluate quality of life according to Functional Assessment of Cancer Therapy Lymphoma Subscale (FACT-Lym) assessment tool



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

3.1.1 IgM paraprotein identified on serum immunofixation electrophoresis OR light chain-restricted CD20+ lymphoplasmacytic population on biopsy of bone marrow or lymph node (identified by H&E/immunohistochemistry or flow cytometry) OR positive myeloid differentiation primary response gene 88 (MYD88-L265P) OR CXCR4WHIM mutation (CXCR4 mutation - warts, hypogammaglobulinemia, infections, myelokathexis) on submitted samples

3.1.2 Biopsy-proven relapsed or refractory AL amyloidosis

3.1.3 Age ≥ 18 years

3.1.4 Eastern Cooperative Oncology Group (ECOG) performance status <2 (see Appendix A.)

3.1.5 Difference between serum free light chains (FLC) of >30 mg/L or quantifiable IgM paraprotein >0.5 g/L

3.1.6 Participants must have normal organ and marrow function as defined below:

  • Absolute neutrophil count > 1,000/mm3
  • Platelets > 50,000/mm3

3.1.7 Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

3.2.1 Previous treatment with idelalisib

3.2.2 Glomerular filtration rate (GFR) <15 ml/min

3.2.3 Cardiac biomarker Stage III disease as determined by B-type natriuretic peptide (BNP) >100 pg/mL and Troponin-I >0.1 ng/mL (Girnius 2014)

3.2.4 alanine-aminotransferase (ALT)/aspartate aminotransferase (AST) values >2.5x upper limit of normal, Bilirubin >1.5 upper limit of normal (ULN)

3.2.5 Central nervous system (CNS) malignancy or other active malignancy

3.2.6 Lactating or pregnant women

3.2.7 Exposure to another investigational drug within 4 weeks prior to start of study treatment

3.2.8 Ongoing alcohol or drug addiction as determined by investigator

3.2.9 Amyloid-directed therapy within the past 28 days

3.2.10 History of Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV) (assessed by positive Hepatitis B polymerase chain reaction assay (PCR) or Hepatitis B Surface Antigen), and/or Hepatitis C Virus (HCV) infection

3.2.11 t(11,14) translocation identified on bone marrow cytogenetics or by Fluorescence in situ hybridization (FISH)

3.2.12 Known lytic bone lesions

3.2.13 Positive cytomegaly virus (CMV) Polymerase chain reaction (PCR)

3.2.14 Previously untreated AL amyloidosis (Newly diagnosed)

3.2.15 Unwilling or unable to comply with the protocol


Information from the National Library of Medicine

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): NCT02590588


Locations
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United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
John Mark Sloan
Gilead Sciences
Investigators
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Principal Investigator: John "Mark" Sloan, MD Boston Medical Center
  Study Documents (Full-Text)

Documents provided by John Mark Sloan, Boston Medical Center:
Informed Consent Form  [PDF] June 14, 2016


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Responsible Party: John Mark Sloan, Associate Professor of Medicine, Boston Medical Center
ClinicalTrials.gov Identifier: NCT02590588     History of Changes
Other Study ID Numbers: H-34318
First Posted: October 29, 2015    Key Record Dates
Results First Posted: May 10, 2017
Last Update Posted: September 21, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by John Mark Sloan, Boston Medical Center:
IgM-associated AL amyloidosis

Additional relevant MeSH terms:
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Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Idelalisib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action