Back to results

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

Primary Purpose

Amyloidosis

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Idelalisib

About this trial

This is an interventional treatment trial for Amyloidosis focused on measuring IgM-associated AL amyloidosis

Eligibility Criteria

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

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

Sites / Locations

Boston Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Idelalisib

Arm Description

Idelalisib 100 mg twice daily with possible escalation after 3 months to 150 mg twice daily at investigator discretion.

Outcomes

Primary Outcome Measures

Overall Response

Evaluate hematologic response according to standard criteria

Secondary Outcome Measures

Progression Free Survival

Evaluate time to progression

Organ Response

Number of patients with organ response using standard AL amyloidosis criteria.

Evaluate Safety and Tolerability of Agent

Number of Participants With Treatment-Related Adverse Events as Assessed by Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0

Quality of Life

Evaluate quality of life according to Functional Assessment of Cancer Therapy Lymphoma Subscale (FACT-Lym) assessment tool

Full Information

NCT ID

NCT02590588

First Posted

September 9, 2015

Last Updated

August 23, 2017

Sponsor

John Mark Sloan

Collaborators

Gilead Sciences

1. Study Identification

Unique Protocol Identification Number

NCT02590588

Brief Title

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

Official Title

Study of Phosphatidylinositol-3-kinase (PI3K) Inhibitor, Idelalisib (GS-1101), in IgM-Associated AL Amyloid

Study Type

Interventional

2. Study Status

Record Verification Date

August 2017

Overall Recruitment Status

Terminated

Why Stopped

Poor accrual

Study Start Date

January 2016 (Actual)

Primary Completion Date

March 27, 2017 (Actual)

Study Completion Date

March 27, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

John Mark Sloan

Collaborators

Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyloidosis

Keywords

IgM-associated AL amyloidosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Idelalisib

Arm Type

Experimental

Arm Description

Idelalisib 100 mg twice daily with possible escalation after 3 months to 150 mg twice daily at investigator discretion.

Intervention Type

Drug

Intervention Name(s)

Idelalisib

Other Intervention Name(s)

GS-1101

Intervention Description

Idelalisib daily until unacceptable toxicity or disease progression.

Primary Outcome Measure Information:

Title

Overall Response

Description

Evaluate hematologic response according to standard criteria

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Progression Free Survival

Description

Evaluate time to progression

Time Frame

1 year

Title

Organ Response

Description

Number of patients with organ response using standard AL amyloidosis criteria.

Time Frame

3 months

Title

Evaluate Safety and Tolerability of Agent

Description

Number of Participants With Treatment-Related Adverse Events as Assessed by Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0

Time Frame

3 months

Title

Quality of Life

Description

Evaluate quality of life according to Functional Assessment of Cancer Therapy Lymphoma Subscale (FACT-Lym) assessment tool

Time Frame

3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John "Mark" Sloan, MD

Organizational Affiliation

Boston Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Boston Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02118

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs