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

Primary Purpose

Amyloidosis

Status

Completed

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

Bortezomib

dexamethasone

filgrastim

autologous hematopoietic stem cell transplantation (ASCT)

Melphalan

About this trial

This is an interventional treatment trial for Amyloidosis focused on measuring AL amyloidosis, bortezomib, autologous stem cell transplantation

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

BD induction followed by ASCT

ASCT alone

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Number of participants with hematologic complete response between BD+ASCT arm and ASCT alone arm in the treatment of AL amyloidosis

Secondary Outcome Measures

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Number of participants with organ responses between BD+ASCT arm and ASCT alone arm in the treatment of AL amyloidosis

Overall survival

Progression free survival

Full Information

NCT ID

NCT01998503

First Posted

November 15, 2013

Last Updated

November 25, 2013

Sponsor

Nanjing University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT01998503

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2013

Overall Recruitment Status

Completed

Study Start Date

December 2007 (undefined)

Primary Completion Date

June 2013 (Actual)

Study Completion Date

August 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Nanjing University School of Medicine

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyloidosis

Keywords

AL amyloidosis, bortezomib, autologous stem cell transplantation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

56 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BD induction followed by ASCT

Arm Type

Active Comparator

Arm Description

Arm Title

ASCT alone

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Bortezomib

Other Intervention Name(s)

Velcade

Intervention Type

Drug

Intervention Name(s)

dexamethasone

Intervention Description

Given orally

Intervention Type

Biological

Intervention Name(s)

filgrastim

Intervention Description

Given subcutaneous

Intervention Type

Procedure

Intervention Name(s)

autologous hematopoietic stem cell transplantation (ASCT)

Intervention Description

Given on day 0

Intervention Type

Drug

Intervention Name(s)

Melphalan

Primary Outcome Measure Information:

Title

Number of participants with hematologic complete response between BD+ASCT arm and ASCT alone arm in the treatment of AL amyloidosis

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Time Frame

12 months

Title

Number of participants with organ responses between BD+ASCT arm and ASCT alone arm in the treatment of AL amyloidosis

Time Frame

12 months

Title

Overall survival

Time Frame

24 months

Title

Progression free survival

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhihong Liu, MD

Organizational Affiliation

Jinling Hospital, China

Official's Role

Principal Investigator

Facility Information:

Facility Name

Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine

City

Nanjing

State/Province

Jiangsu

ZIP/Postal Code

210002

Country

China

12. IPD Sharing Statement

Citations:

PubMed Identifier

24386911

Citation

Huang X, Wang Q, Chen W, Zeng C, Chen Z, Gong D, Zhang H, Liu Z. Induction therapy with bortezomib and dexamethasone followed by autologous stem cell transplantation versus autologous stem cell transplantation alone in the treatment of renal AL amyloidosis: a randomized controlled trial. BMC Med. 2014 Jan 6;12:2. doi: 10.1186/1741-7015-12-2.

Results Reference

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

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