Idelalisib for Immunoglobulin M (IgM)-Associated Primary (AL) Amyloidosis
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| 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.
Study Design
Arms and Interventions
| 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 Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Response [3 months]
Evaluate hematologic response according to standard criteria
Secondary Outcome Measures
- Progression Free Survival [1 year]
Evaluate time to progression
- Organ Response [3 months]
Number of patients with organ response using standard AL amyloidosis criteria.
- Evaluate Safety and Tolerability of Agent [3 months]
Number of Participants With Treatment-Related Adverse Events as Assessed by Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0
- Quality of Life [3 months]
Evaluate quality of life according to Functional Assessment of Cancer Therapy Lymphoma Subscale (FACT-Lym) assessment tool
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Boston Medical Center | Boston | Massachusetts | United States | 02118 |
Sponsors and Collaborators
- John Mark Sloan
- Gilead Sciences
Investigators
- Principal Investigator: John "Mark" Sloan, MD, Boston Medical Center
Study Documents (Full-Text)
More Information
Publications
None provided.- H-34318
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Idelalisib |
|---|---|
| Arm/Group Description | Idelalisib 100 mg twice daily with possible escalation after 3 months to 150 mg twice daily at investigator discretion. Idelalisib: Idelalisib daily until unacceptable toxicity or disease progression. |
| Period Title: Overall Study | |
| STARTED | 1 |
| COMPLETED | 0 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Idelalisib |
|---|---|
| Arm/Group Description | Idelalisib 100 mg twice daily with possible escalation after 3 months to 150 mg twice daily at investigator discretion. Idelalisib: Idelalisib daily until unacceptable toxicity or disease progression. |
| Overall Participants | 1 |
| Overall only patient enrolled | 1 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
1
100%
|
| >=65 years |
0
0%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
1
100%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
1
100%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
Outcome Measures
| Title | Overall Response |
|---|---|
| Description | Evaluate hematologic response according to standard criteria |
| Time Frame | 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants with hematologic response is zero. There was only one patient enrolled and he did not remain on study long enough for his first 3 month response evaluation. |
| Arm/Group Title | Idelalisib |
|---|---|
| Arm/Group Description | Idelalisib 100 mg twice daily with possible escalation after 3 months to 150 mg twice daily at investigator discretion. Idelalisib: Idelalisib daily until unacceptable toxicity or disease progression. |
| Measure Participants | 0 |
| Title | Progression Free Survival |
|---|---|
| Description | Evaluate time to progression |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| The evaluation of progression-free survival requires that a patient responds, and then progresses. There was only one patient enrolled and he did not remain on study long enough for his first 3 month response evaluation. |
| Arm/Group Title | Idelalisib |
|---|---|
| Arm/Group Description | Idelalisib 100 mg twice daily with possible escalation after 3 months to 150 mg twice daily at investigator discretion. Idelalisib: Idelalisib daily until unacceptable toxicity or disease progression. |
| Measure Participants | 0 |
| Title | Organ Response |
|---|---|
| Description | Number of patients with organ response using standard AL amyloidosis criteria. |
| Time Frame | 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of patients with organ response using standard AL amyloidosis criteria. |
| Arm/Group Title | Idelalisib |
|---|---|
| Arm/Group Description | Idelalisib 100 mg twice daily with possible escalation after 3 months to 150 mg twice daily at investigator discretion. Idelalisib: Idelalisib daily until unacceptable toxicity or disease progression. |
| Measure Participants | 0 |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| There was only one patient enrolled and he did experience treatment-related adverse events. |
| Arm/Group Title | Idelalisib |
|---|---|
| Arm/Group Description | Idelalisib 100 mg twice daily with possible escalation after 3 months to 150 mg twice daily at investigator discretion. Idelalisib: Idelalisib daily until unacceptable toxicity or disease progression. |
| Measure Participants | 1 |
| Count of Participants [Participants] |
1
100%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 'There was only one patient enrolled and he did not remain on study long enough for his first protocol-specified quality of life assessment |
| Arm/Group Title | Idelalisib |
|---|---|
| Arm/Group Description | Idelalisib 100 mg twice daily with possible escalation after 3 months to 150 mg twice daily at investigator discretion. Idelalisib: Idelalisib daily until unacceptable toxicity or disease progression. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | 2 months | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Idelalisib | |
| Arm/Group Description | Idelalisib 100 mg twice daily with possible escalation after 3 months to 150 mg twice daily at investigator discretion. Idelalisib: Idelalisib daily until unacceptable toxicity or disease progression. | |
All Cause Mortality |
||
| Idelalisib | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/1 (0%) | |
Serious Adverse Events |
||
| Idelalisib | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/1 (100%) | |
| Investigations | ||
| increased | 1/1 (100%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Idelalisib | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/1 (100%) | |
| Eye disorders | ||
| swollen eyelids | 1/1 (100%) | 1 |
| Gastrointestinal disorders | ||
| nausea | 1/1 (100%) | 1 |
| diarrhea | 1/1 (100%) | 1 |
| vomiting | 1/1 (100%) | 1 |
| diminished appetite | 1/1 (100%) | 1 |
| Investigations | ||
| discolored urine | 1/1 (100%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Mark Sloan MD |
|---|---|
| Organization | Boston Medical Center |
| Phone | 617-638-2367 |
| mark.sloan@bmc.org |
- H-34318