- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00030381
Iododoxorubicin in Treating Patients With Primary Systemic Amyloidosis
Phase I Trial of 4'-IODO-4'-Deoxydoxorubicin in Primary Amyloidosis (AL)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of iododoxorubicin in patients with primary systemic amyloidosis.
SECONDARY OBJECTIVES:
I. Determine the safety, especially cardiac safety, of this drug in these patients.
II. Determine the survival rate of patients treated with this drug. III. Determine, preliminarily, the clinical efficacy of this drug in these patients.
IV. Determine the pharmacokinetics of this drug in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive iododoxorubicin IV over 15 minutes on days 1, 8, 15, and 22. Treatment repeats every 12 weeks for a total of 4 courses or a cumulative dose of 400 mg/m^2 in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of iododoxorubicin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed at 3 months.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histochemically confirmed amyloidosis by polarizing microscopy of greenbirefringent material in Congo red-stained tissue specimens
At least one of the following:
- Demonstrable M-protein in serum or urine
- Clonal population of plasma cells in bone marrow
- Immunohistochemical stain with anti-light chain antisera of amyloid fibrils
Symptomatic organ involvement, including liver involvement, mild cardiac involvement, renal involvement, grade 1 or 2 peripheral neuropathy, or soft tissue involvement (including tongue)
- No purpura or carpal tunnel syndrome as sole manifestation of disease
No clinically overt multiple myeloma defined as monoclonal bone marrow platelet concentration greater than 20% and at least one of the following:
- Bone lesions
- Anemia
- Hypercalcemia
- Performance status - ECOG 0-3 (3 allowed only if related to muscular infiltration by amyloid or peripheral neuropathy)
- Platelet count at least 100,000/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Total bilirubin no greater than 2.0 mg/dL
- Direct bilirubin no greater than 1.0 mg/dL
- Alkaline phosphatase no greater than 4 times upper limit of normal (ULN)
- AST or ALT no greater than 3 times ULN
- Creatinine clearance at least 40 mL/min
- Ejection fraction at least 50% by echocardiogram
- No New York Heart Association class III or IV heart disease
- No enzyme-documented myocardial infarction within the past 3 years
- No chronic atrial fibrillation
- No grade 2 or 3 atrioventricular block (Mobitz type I allowed)
- No sustained (greater than 30 seconds) ventricular tachycardia, more than 1 episode of non-sustained ventricular tachycardia (3 consecutive ventricular beats), or frequent (more than 20 in 24 hours) ventricular pairs by 24-hour ambulatory electrocardiographic monitoring
- No intraventricular septum greater than 16 mm by echocardiogram
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No uncontrolled infection
- No other active malignancy except nonmelanoma skin cancer or cervical cancer
- No psychiatric illness or social situation that would preclude study
- No severe diarrhea (greater than grade 3) that is not controllable with medication or that requires total parenteral nutrition
- More than 4 weeks since prior interferon alfa
- No concurrent immunotherapy
- More than 4 weeks since prior melphalan or other alkylating agents
- No prior anthracycline exposure greater than 120 mg/m^2
- Recovered from prior chemotherapy
- No other concurrent chemotherapy
- More than 4 weeks since prior high-dose dexamethasone
- No concurrent radiotherapy
- No concurrent investigational ancillary therapy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (iododoxorubicin)
Patients receive iododoxorubicin IV over 15 minutes on days 1, 8, 15, and 22. Treatment repeats every 12 weeks for a total of 4 courses or a cumulative dose of 400 mg/m^2 in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MTD of IDOX defined as the highest safely-tolerated dose where =< 1 patient experiences DLT with the next higher dose having at least 2 patients who experience DLT
Time Frame: 12 weeks
|
The number and severity of toxicity incidents will indicate the level of tolerance of IDOX in the treatment of primary amyloidosis.
Non-hematologic toxicities will be evaluated via the ordinal CTC standard toxicity grading.
Hematologic toxicity measures of thrombocytopenia, neutropenia and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via CTC standard toxicity grading.
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Laboratory correlates
Time Frame: Up to 3 months post treatment
|
Descriptive statistics and simple scatterplots will form the basis of presentation of these data.
Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and non-parametric correlation procedures (Pearson's and Spearman's coefficients).
Prerequisite normality testing of these data will be carried out via standard Shapiro and Wilk (25) testing.
|
Up to 3 months post treatment
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Angela Dispenzieri, Mayo Clinic
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Paraproteinemias
- Proteostasis Deficiencies
- Neoplasms, Plasma Cell
- Immunoglobulin Light-chain Amyloidosis
- Amyloidosis
- Antineoplastic Agents
- Antibiotics, Antineoplastic
- Esorubicin
Other Study ID Numbers
- NCI-2012-02443
- U01CA069912 (U.S. NIH Grant/Contract)
- MC0113
- CDR0000069160 (Registry Identifier: PDQ (Physician Data Query))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Primary Systemic Amyloidosis
-
PETHEMA FoundationCompletedPrimary Systemic AmyloidosisSpain
-
The Cleveland ClinicCompletedPrimary Systemic Amyloidosis
-
Medical College of WisconsinNational Heart, Lung, and Blood Institute (NHLBI)CompletedPrimary Systemic AmyloidosisUnited States
-
University Hospital, LimogesMinistry of Health, FranceCompletedPrimary Systemic Amyloidosis (AL)France
-
Mayo ClinicCompletedPrimary Systemic AmyloidosisUnited States
-
National Cancer Institute (NCI)CompletedPrimary Systemic Amyloidosis | Light Chain Deposition DiseaseUnited States
-
Prothena Biosciences Ltd.TerminatedPrimary Systemic (AL) AmyloidosisUnited States, Spain, Israel, Canada, Poland, Netherlands, France, Germany, United Kingdom, Belgium, Denmark, Greece, Australia, Austria, Italy
-
Barbara Ann Karmanos Cancer InstituteNational Cancer Institute (NCI)TerminatedPrimary Systemic Amyloidosis | Light Chain Deposition DiseaseUnited States, Canada
-
Barbara Ann Karmanos Cancer InstituteNational Cancer Institute (NCI)CompletedPrimary Systemic Amyloidosis | Light Chain Deposition DiseaseUnited States
-
M.D. Anderson Cancer CenterTakeda; Janssen PharmaceuticalsActive, not recruitingRecurrent Primary Amyloidosis | Refractory Primary Amyloidosis | Newly Diagnosed Primary AmyloidosisUnited States
Clinical Trials on pharmacological study
-
National Cancer Institute (NCI)TerminatedUnspecified Adult Solid Tumor, Protocol SpecificUnited States
-
National Cancer Institute (NCI)CompletedExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue | Nodal Marginal Zone B-cell Lymphoma | Recurrent Adult Burkitt Lymphoma | Recurrent Adult Diffuse Large Cell Lymphoma | Recurrent Adult Diffuse Mixed Cell Lymphoma | Recurrent Adult Diffuse Small Cleaved Cell Lymphoma and other conditionsUnited States
-
Universitätsmedizin MannheimHeidelberg UniversityUnknownLung Cancer | Brain and Central Nervous System TumorsGermany
-
Sidney Kimmel Comprehensive Cancer Center at Johns...National Cancer Institute (NCI); Peloton Therapeutics, Inc.CompletedRecurrent GlioblastomaUnited States
-
National Cancer Institute (NCI)TerminatedUnspecified Adult Solid Tumor, Protocol SpecificUnited States
-
National Cancer Institute (NCI)CompletedUnspecified Childhood Solid Tumor, Protocol Specific | Recurrent Childhood Soft Tissue Sarcoma | Recurrent Childhood Brain Stem Glioma | Recurrent Childhood Visual Pathway Glioma | Childhood Central Nervous System Germ Cell Tumor | Childhood Central Nervous System Choriocarcinoma | Childhood Central... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedUnspecified Adult Solid Tumor, Protocol SpecificUnited States
-
National Cancer Institute (NCI)TerminatedRecurrent Cutaneous T-cell Non-Hodgkin Lymphoma | Recurrent Mycosis Fungoides/Sezary SyndromeUnited States
-
National Cancer Institute (NCI)CompletedUnspecified Adult Solid Tumor, Protocol Specific | Male Breast Cancer | Stage IV Breast Cancer | Stage IV Ovarian Epithelial Cancer | Stage IV Renal Cell Cancer | Recurrent Renal Cell Cancer | Recurrent Breast Cancer | Recurrent Ovarian Epithelial Cancer | Recurrent Primary Peritoneal Cavity Cancer | Stage...United States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedMyeloid Proliferations Associated With Down SyndromeUnited States, Canada, Australia, Puerto Rico