Human Immune Globulin in Treating Patients With Primary Amyloidosis That is Causing Heart Dysfunction

• Sponsor: University of Tennessee (Other)
• Overall Status: Completed
• CT.gov ID: NCT00547365
• Collaborator: (none)
• Enrollment: 10
• Locations: 2
• Arm: 1
• Duration (Months): 45
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma; Plasma Cell Neoplasm	Biological: Human immune globulin intravenous (IGIV)	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Therapeutic Potential of Human Immune Globulin Intravenous (IGIV) in Patients With Cardiac-Associated Light Chain (AL) Amyloidosis
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Human immune globulin intravenous (IGIV) Analyze the therapeutic potential of human immune globulin intravenous (IGIV) when given to patients with cardiac-associated AL amyloidosis	Biological: Human immune globulin intravenous (IGIV); Analyze the therapeutic potential of human immune globulin intravenous (IGIV) when given to patients with cardiac-associated AL amyloidosis

Outcome Measures

Primary Outcome Measures

1. 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]

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Baptist Regional Cancer Center at Baptist Riverside	Knoxville	Tennessee	United States	37901
2	St. Mary's Medical Center	Powell	Tennessee	United States	37849

Sponsors and Collaborators

• University of Tennessee

Investigators

• Study Chair: Alan Solomon, MD, St. Mary's Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alan Solomon, Professor of Medicine, University of Tennessee
• ClinicalTrials.gov Identifier: NCT00547365
• Other Study ID Numbers: CDR0000572104; BRCC-BHS-06127; UTCI-2645
• First Posted: Oct 22, 2007
• Last Update Posted: Sep 19, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by Alan Solomon, Professor of Medicine, University of Tennessee: primary systemic amyloidosis
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Amyloidosis; Immunoglobulins; Antibodies; gamma-Globulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin

Study Results

Participant Flow

Recruitment Details	Overall study length - 2007-2011; Location - medical clinic
Pre-assignment Detail	Patients with primary light-chain (AL)-associated amyloidosis that caused heart dysfunction were on study.

Arm/Group Title	Human Immune Globulin Intravenous (IGIV)
Arm/Group Description	The therapeutic potential of human immune globulin intravenous (IGIV)was evaluated in patients with cardiac-associated AL amyloidosis. Patients received, via intravenous infusion, 30-40 gm of IGIV (depending on body weight) weekly for 3 months and then every other week for the next 9 months.The total time to complete the study was ~1 yr.
Period Title: Overall Study
STARTED	10
COMPLETED	2
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Human Immune Globulin Intravenous (IGIV)
Arm/Group Description
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 40%
>=65 years	6 60%
Sex: Female, Male (Count of Participants)
Female	5 50%
Male	5 50%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

All patients who had at least one infusion of human immune globulin intravenous.

Arm/Group Title	Human Immune Globulin Intravenous (IGIV)
Arm/Group Description	Immune globulin intravenous (IGIV) was administered to patients with cardiac-dominant AL amyloidosis in order to determine its therapeutic potential or possible toxicity when given to subjects weekly for 3 months and then every other week for the next 9 months. Response was evaluated by changes in serum anti-fibril antibody levels, changes in BNP (B-type natriuretic peptide) levels and IVS (interventricular septum) thickness.
Measure Participants	10
Number [events]	0

2. Primary Outcome

Title	Clinical Response of Patients With Cardiac-dominant AL Amyloidosis Given Human Immune Globulin Intravenous (IGIV)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Human Immune Globulin Intravenous (IGIV)
Arm/Group Description	Human immune globulin intravenous (IGIV) was infused into 10 patients with cardiac-associated AL amyloidosis and its therapeutic potential evaluated through measurement of serum anti-fibril IgG antibody levels, as well as amyloid burden, pre- and post-administration.
Measure Participants	2
Number [participants with positive response]	1 10%

Adverse Events

Arm/Group Title	Human Immune Globulin Intravenous (IGIV)
Arm/Group Description	Therapeutic potential of human immune globulin intravenous (IGIV)in patients with cardiac-associated AL amyloidosis
All Cause Mortality
	Human Immune Globulin Intravenous (IGIV)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Human Immune Globulin Intravenous (IGIV)
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Human Immune Globulin Intravenous (IGIV)
	Affected / at Risk (%)	# Events
Total	0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.