AL Amyloidosis
Conditions
Keywords
AL Amyloidosis, Stem Cell Transplantation
Brief summary
Standard treatment for AL Amyloidosis is high-dose melphalan and stem cell transplant. This study will compare the safety and effectiveness of standard treatment with high-dose melphalan and stem cell transplant, compared with investigational bortezomib when used in combination with standard treatment with high-dose melphalan and stem cell transplant for AL amyloidosis.
Detailed description
This study seeks to enroll patients with AL amyloidosis who have been recommended for standard treatment with high-dose melphalan and stem cell transplant. Standard treatment for this disease is high-dose melphalan and stem cell transplant. The purpose of this study is to compare the safety and effectiveness of standard treatment with high-dose melphalan and stem cell transplant, compared with investigational bortezomib when used in combination with standard treatment with high-dose melphalan and stem cell transplant for AL amyloidosis. Patients enrolled in this study will receive either standard treatment with high-dose melphalan and stem cell transplant, or investigational bortezomib used in combination with standard treatment with high-dose melphalan and stem cell transplant.
Interventions
DRUGBortezomib
Conditioning Regimen: Drug: Bortezomib: 1.0 mg/m2/dose D -6, D -3, D +1, D + 4 Drug: Melphalan: 70-100 mg/m2/dose D -2, D -1
DRUGMelphalan
Conditioning Regimen: Drug: Melphalan: 70-100 mg/m2/dose D -2, D -1 Stem Cell Transplant: D 0
DRUGNeupogen
granulocyte colony-stimulating factor (G-CSF) mobilization 16mcg/kg x 4 days
PROCEDUREStem Cell Collection
collect at least 2.5 million cluster of differentiation 34 (CD34)+ stem cells
PROCEDUREStem cell infusion
infusion of previously collected autologous stem cells
Sponsors
Boston Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histological diagnosis of primary systemic (AL) amyloidosis based on: * Deposition of amyloid material by Congo red stain showing characteristic apple green birefringence,AND… * evidence of a clonal plasma cell dyscrasia with monoclonal protein in the serum or urine by immunofixation electrophoresis studies AND/OR abnormal serum free light chain assay AND/OR clonal plasma cells in the bone marrow exam demonstrated by immunohistochemistry, flow cytometry or in situ hybridization AND… * evidence of organ involvement other than carpal tunnel syndrome. Patients with senile, secondary, localized, dialysis-related or familial amyloidosis are not eligible. Confirmation of tissue diagnosis at all sites of organ dysfunction is encouraged, but not required. 2. Patients must be \> 18 years of age. 3. Patients must have a performance status of 0-2 by Eastern Cooperative Oncology Group (ECOG) criteria 4. Patients must have left ventricular ejection fraction (LVEF) \> 45% by echocardiogram within 60 days of enrollment 5. Pulmonary Function Tests must show diffusing capacity of lung for carbon monoxide (DLCO) \> 50%. 6. All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
Exclusion criteria
1. Patients with recent (\< 6 months) myocardial infarction, congestive heart failure, New York Heart Association (NYHA) class III/IV or arrhythmia which are refractory to medical therapy are ineligible. 2. Prior chemotherapy with alkylating agent allowed only if no evidence of Myelodysplastic Dysplastic Syndrome (MDS) morphologically or cytogenetically. Total cumulative dose of oral melphalan must be \< 300 mg. Patients should not have received any cytotoxic therapy \< 4 weeks prior to registration and should have fully recovered from the effects of such therapy. 3. Patients must not have overt multiple myeloma (\>30% bone marrow plasmacytosis and, extensive (\>2) lytic lesions and hypercalcemia). 4. No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years. 5. Patients must not be HIV positive. 6. Pregnant or nursing women may not participate. Women and men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hematologic Response | 6 months | Hematologic response defined as: at least 50% improvement in the difference between involved and uninvolved free light chains |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicities | 100 days | Number of serious adverse events per participant based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 |
| Overall Survival | 5 years | duration of overall survival measured in days |
| Number of Participants With Organ Response | 5 years | analysis of number of patients with organ response, as defined on page 13 of the detailed protocol for kidney, heart and liver. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Melphalan Neupogen 16mcg/kg x 4 days Stem cell collection Drug: high dose melphalan 140 or 200 mg/m2 stem cell infusion
Melphalan: Conditioning Regimen:
Drug: Melphalan: 70-100 mg/m2/dose D -2, D -1 Stem Cell Transplant: D 0
Neupogen: granulocyte colony-stimulating factor (G-CSF) mobilization 16mcg/kg x 4 days
Stem Cell Collection: collect at least 2.5 million cluster of differentiation 34 (CD34)+ stem cells
Stem cell infusion: infusion of previously collected autologous stem cells | 2 |
| Melphalan + Bortezomib Neupogen 16mcg/kg x 4 days Stem Cell collection drug: high-dose melphalan 140 or 200 mg/m2 drug: Bortezomib 1.0 mg/m2/dose x 4 doses stem cell infusion
Bortezomib: Conditioning Regimen:
Drug: Bortezomib: 1.0 mg/m2/dose D -6, D -3, D +1, D + 4 Drug: Melphalan: 70-100 mg/m2/dose D -2, D -1
Melphalan: Conditioning Regimen:
Drug: Melphalan: 70-100 mg/m2/dose D -2, D -1 Stem Cell Transplant: D 0
Neupogen: granulocyte colony-stimulating factor (G-CSF) mobilization 16mcg/kg x 4 days
Stem Cell Collection: collect at least 2.5 million cluster of differentiation 34 (CD34)+ stem cells
Stem cell infusion: infusion of previously collected autologous stem cells | 1 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
Baseline characteristics
| Characteristic | Melphalan | Melphalan + Bortezomib | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 1 / 1 |
| other Total, other adverse events | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 2 / 2 | 1 / 1 |
Outcome results
Primary
Number of Participants With Hematologic Response
Hematologic response defined as: at least 50% improvement in the difference between involved and uninvolved free light chains
Time frame: 6 months
Population: Two participants were not evaluable as they expired and did not have a post-treatment response evaluation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Melphalan | Number of Participants With Hematologic Response | 0 Participants |
| Melphalan + Bortezomib | Number of Participants With Hematologic Response | 0 Participants |
Secondary
Number of Participants With Organ Response
analysis of number of patients with organ response, as defined on page 13 of the detailed protocol for kidney, heart and liver.
Time frame: 5 years
Population: Due to early termination, organ response data was not collected.
Secondary
Overall Survival
duration of overall survival measured in days
Time frame: 5 years
Population: The protocol was closed prior to the 5-year period of assessment, so 5-year survival assessment of only two participants was assessed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Melphalan | Overall Survival | 43 days |
| Melphalan + Bortezomib | Overall Survival | 29 days |
Secondary
Toxicities
Number of serious adverse events per participant based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Time frame: 100 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Melphalan | Toxicities | 8.5 events per participant |
| Melphalan + Bortezomib | Toxicities | 15 events per participant |