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

Amyloidosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01998503
• Other study ID #: NJCT-0703
• Status: Completed
• Phase: Phase 3
• First received: November 15, 2013
• Last updated: November 25, 2013
• Start date: December 2007
• Est. completion date: August 2013

Study information

• Verified date: November 2013
• Source: Nanjing University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: August 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyloidosis

Intervention

Drug:
• Bortezomib

• dexamethasone
Given orally

Biological:
• filgrastim
Given subcutaneous

Procedure:
• autologous hematopoietic stem cell transplantation (ASCT)
Given on day 0

Drug:
• Melphalan

Locations

Country	Name	City	State
China	Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Nanjing University School of Medicine

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with hematologic complete response between BD+ASCT arm and ASCT alone arm in the treatment of AL amyloidosis		12 months	No
Secondary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability		12 months	Yes
Secondary	Number of participants with organ responses between BD+ASCT arm and ASCT alone arm in the treatment of AL amyloidosis		12 months	No
Secondary	Overall survival		24 months	No
Secondary	Progression free survival		24 months	No