Bortezomib and Dexamethasone Followed by ASCT Compared With ASCT Alone in Treating Patients With AL Amyloidosis

Study Overview
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Brief Summary
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This randomized phase III trial is studying the side effects and how well giving induction therapy with bortezomib and dexamethasone followed by autologous stem cell transplantation (ASCT) compared with ASCT alone in treating patients with newly diagnosed renal AL amyloidosis. In this prospective, randomized control study, patients with newly diagnosed AL amyloidosis who met the criteria for ASCT were randomized to receive 2 cycles of BD as induction therapy followed by ASCT (BD+ASCT) (arm 1) or to receive ASCT alone as an initial treatment (arm 2). Hematologic and organ responses were evaluated every 3 months after ASCT. All the patients should be followed up for 12 months.

Detailed Description
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Arm 1: The BD regimen included bortezomib 1.3 mg/m2 i.v. and dexamethasone 40 mg p.o. on days 1, 4, 8 and 11 of the 21 day cycle. This process was repeated for 2 cycles. After two cycles of BD therapy, the collection of peripheral blood stem cells (PBSC) should be completed within 4 weeks. Recommended dose of drug is as follows: granulocyte colony-stimulating factor (G-CSF) 5-10ug/kg on days 1-5 will be given, then peripheral blood stem cells will be collected on days 5-6 for 2×10^6 CD34+ cells /kg. Patients will receive ASCT therapy in 8 weeks after collection of PBSC (Recorded as day 0), while melphalan (day -2) with a dose of 140 or 200 mg/m2 (choosing a dose according to the degree of risk for patients). Melphalan will be administered by central venous catheter. Arm 2: the patients who assigned to arm 2 will receive ASCT alone as an initial treatment. The process of ASCT is as same as arm 1.

Official Title
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Induction Therapy With Bortezomib and Dexamethasone Followed by Autologous Stem Cell Transplantation Versus Autologous Stem Cell Transplantation Alone in the Treatment of AL Amyloidosis

Conditions
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Amyloidosis

Intervention / Treatment
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* Drug: Bortezomib
* Drug: dexamethasone
* Biological: filgrastim
* Procedure: autologous hematopoietic stem cell transplantation (ASCT)
* Drug: Melphalan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly diagnosed AL amyloidosis Abnormal M protein or free light chain detected in serum and/or urine ECOG score 0-2 points No absolute neutrophil count of ANC less than or equal to 1000 within 14 days before enrollment No platelet count of less than or equal to 50K within 14 days before enrollment Serum bilirubin must lower than 2.0 mg/dl within 14 days before enrollment Serum creatinine must lower than 2.0 mg/dl within 14 days before enrollment Must have LVEF at least 45% by ECHO within 14 days of enrollment Pulmonary Function Tests must show DLCO at least 50% Exclusion Criteria: Subjects have received or are currently receiving systematic treatment with steroids (not including an emergent short-term use of steroids before randomization up to 4 days, maximum dose of 40mg/d) Pregnant and breastfeeding women, delivery term women or unwilling to take birth control measures during the study Subjects suffering from multiple myeloma Grade 2 or more than grade 2 peripheral neuropathy or neuropathic pain according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3 Known or suspected hypersensitivity to dexamethasone, bortezomib, mannitol, boron, or heparin (if use catheters) Subjects suffering from uncontrolled or severe cardiovascular disease, including myocardial infarction, class III-IV heart failure defined by New York Heart Association (NYHA), uncontrolled angina, clinical significant pericardial disease or cardiac amyloidosis (Other contraindications are not suitable for transplant patients) within 6 months before enrollment Subjects suffering from serious physical disease and mental illnesses which may interfere the study Subjects receiving other pilot study or treatment within 4 weeks before enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BD induction followed by ASCT<br>The BD regimen included bortezomib 1.3 mg/m2 i.v. and dexamethasone 40 mg p.o. on days 1, 4, 8 and 11 of the 21 day cycle. This process was repeated for 2 cycles. After two cycles of BD therapy, the collection of peripheral blood stem cells (PBSC) should be completed within 4 weeks. Patients receive filgrastim (G-CSF) on days 1 to 5 and undergo autologous hematopoietic stem cell (HSC) collection. Patients will receive ASCT therapy in 8 weeks after collection of PBSC (Recorded as day 0), while melphalan (day -2) with a dose of 140 or 200 mg/m2 (choosing a dose according to the degree of risk for patients). Melphalan will be administered by central venous catheter. | Drug: Bortezomib<br> <br> * Other names: Velcade;Drug: dexamethasone<br>* Given orally<br>Biological: filgrastim<br>* Given subcutaneous<br>Procedure: autologous hematopoietic stem cell transplantation (ASCT)<br>* Given on day 0<br>Drug: Melphalan<br> <br> |
| Experimental: ASCT alone<br>the patients who assigned to this arm will receive ASCT alone as an initial treatment. At first, patients receive the collection of peripheral blood stem cells (PBSC), Patients receive filgrastim (G-CSF) on days 1 to 5 and undergo autologous hematopoietic stem cell (HSC) collection. After then patients will receive ASCT therapy in 8 weeks after collection of PBSC (Recorded as day 0), while melphalan (day -2) with a dose of 140 or 200 mg/m2 (choosing a dose according to the degree of risk for patients). Melphalan will be administered by central venous catheter. | Biological: filgrastim<br>* Given subcutaneous<br>Procedure: autologous hematopoietic stem cell transplantation (ASCT)<br>* Given on day 0<br>Drug: Melphalan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with hematologic complete response between BD+ASCT arm and ASCT alone arm in the treatment of AL amyloidosis |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability |  | 12 months | 
| Number of participants with organ responses between BD+ASCT arm and ASCT alone arm in the treatment of AL amyloidosis |  | 12 months | 
| Overall survival |  | 24 months | 
| Progression free survival |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AL amyloidosis, bortezomib, autologous stem cell transplantation