Multiple Myeloma, Plasma Cell Neoplasm
Conditions
Keywords
primary systemic amyloidosis
Brief summary
RATIONALE: Antibodies, such as human immune globulin, can block the growth of abnormal cells in different ways. Some block the ability of abnormal cells to grow and spread. Others find abnormal cells and help kill them or carry cell-killing substances to them. Giving human immune globulin may be effective in treating patients with primary amyloidosis that is causing heart dysfunction. PURPOSE: This phase I/II trial is studying the side effects and best dose of human immune globulin and to see how well it works in treating patients with primary amyloidosis that is causing heart dysfunction.
Detailed description
OBJECTIVES: * Establish the maximum tolerated dose of human immune globulin intravenous (IGIV) given weekly for the first 3 months and then bi-weekly for 9 additional months in patients with cardiac-associated primary light chain-associated (AL) amyloidosis. * Determine the safety, pharmokinetics, and therapeutic efficacy as evidenced by titers of serum fibril-reactive immunoglobulin G (IgG) antibodies pre- and post-IGIV infusions. * Demonstrate stable or improved organ function. OUTLINE: Patients receive human immune globulin IV (IGIV) once weekly for 3 months and then once biweekly for 9 months, for a total of 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection to measure serum anti-fibril antibody titers pre- and post- IGIV infusion for assessing safety and response to treatment.
Interventions
BIOLOGICALHuman immune globulin intravenous (IGIV)
Analyze the therapeutic potential of human immune globulin intravenous (IGIV) when given to patients with cardiac-associated AL amyloidosis
Sponsors
University of Tennessee
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
* Confirmed diagnosis of cardiac-associated primary (AL) amyloidosis based on accepted clinical and laboratory criteria * Patients must have heart involvement as evidenced by elevated serum brain natriuretic peptide (BNP), troponin levels, and/or 2D echocardiography evidence of a thickened intraventricular septum (IVS). * Life expectancy \> 3 months * Prior or concurrent chemotherapy or other drug-based anti-AL regimes allowed
Exclusion criteria
* Non-AL amyloidosis * New York Heart Association (NYH) class IV heart disease * Significant comorbidity (e.g., uncontrolled infection, diabetes, or other serious illnesses)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerance for Human Immune Globulin Intravenous (IGIV), as Reflected by the Number and Severity of Toxicity Incidents Occurring in Ten Patients Receiving at Least One Infusion of IGIV. | Up to 1 year | — |
| Clinical Response of Patients With Cardiac-dominant AL Amyloidosis Given Human Immune Globulin Intravenous (IGIV) | Up to 1 year | Positive clinical response was defined by improvement in heart function in participating patients with cardiac-dominant AL amyloidosis, as demonstrated by increased serum anti-fibril immunoglobulin G (IgG) antibody levels and reduction (or no evident progression) in amyloid burden. |
Countries
United States
Participant flow
Recruitment details
Overall study length - 2007-2011; Location - medical clinic
Pre-assignment details
Patients with primary light-chain (AL)-associated amyloidosis that caused heart dysfunction were on study.
Participants by arm
| Arm | Count |
|---|---|
| Human Immune Globulin Intravenous (IGIV) | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | death (not related to study) | 4 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Violation | 2 |
Baseline characteristics
| Characteristic | Human Immune Globulin Intravenous (IGIV) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Clinical Response of Patients With Cardiac-dominant AL Amyloidosis Given Human Immune Globulin Intravenous (IGIV)
Positive clinical response was defined by improvement in heart function in participating patients with cardiac-dominant AL amyloidosis, as demonstrated by increased serum anti-fibril immunoglobulin G (IgG) antibody levels and reduction (or no evident progression) in amyloid burden.
Time frame: Up to 1 year
Population: Two of ten patients with AL cardiac involvement who received IGIV infusions were analyzed (other eight individuals were removed from study before completion due to death/conditions unrelated to IGIV, loss to follow-up, or physician decision).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Human Immune Globulin Intravenous (IGIV) | Clinical Response of Patients With Cardiac-dominant AL Amyloidosis Given Human Immune Globulin Intravenous (IGIV) | 1 participants with positive response |
Primary
Tolerance for Human Immune Globulin Intravenous (IGIV), as Reflected by the Number and Severity of Toxicity Incidents Occurring in Ten Patients Receiving at Least One Infusion of IGIV.
Time frame: Up to 1 year
Population: All patients who had at least one infusion of human immune globulin intravenous.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Human Immune Globulin Intravenous (IGIV) | Tolerance for Human Immune Globulin Intravenous (IGIV), as Reflected by the Number and Severity of Toxicity Incidents Occurring in Ten Patients Receiving at Least One Infusion of IGIV. | 0 events |