Amyloidosis
Conditions
Keywords
IgM-associated AL amyloidosis
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.
Interventions
DRUGIdelalisib
Idelalisib daily until unacceptable toxicity or disease progression.
Sponsors
Gilead Sciences
John Mark Sloan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response | 3 months | Evaluate hematologic response according to standard criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Idelalisib 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. | 1 |
| Idelalisib 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. | 1 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Idelalisib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Overall Response
Evaluate hematologic response according to standard criteria
Time frame: 3 months
Population: 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.
Secondary
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
Time frame: 3 months
Population: There was only one patient enrolled and he did experience treatment-related adverse events.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Idelalisib | Evaluate Safety and Tolerability of Agent | 1 Participants |
Secondary
Organ Response
Number of patients with organ response using standard AL amyloidosis criteria.
Time frame: 3 months
Population: Number of patients with organ response using standard AL amyloidosis criteria.
Secondary
Progression Free Survival
Evaluate time to progression
Time frame: 1 year
Population: 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.
Secondary
Quality of Life
Evaluate quality of life according to Functional Assessment of Cancer Therapy Lymphoma Subscale (FACT-Lym) assessment tool
Time frame: 3 months
Population: 'There was only one patient enrolled and he did not remain on study long enough for his first protocol-specified quality of life assessment