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

NCT01998503 | Completed Phase 3 DMC

• 1 other identifier: NJCT-0703
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Amyloidosis

Keywords

AL amyloidosis; bortezomib; autologous stem cell transplantation

Outcome Measures

Primary Outcomes (1)

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

  12 months

Secondary Outcomes (4)

• 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

Study Arms (2)

BD induction followed by ASCT

ACTIVE COMPARATOR

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; Drug: dexamethasone; Biological: filgrastim; Procedure: autologous hematopoietic stem cell transplantation (ASCT); Drug: Melphalan

ASCT alone

EXPERIMENTAL

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; Procedure: autologous hematopoietic stem cell transplantation (ASCT); Drug: Melphalan

Interventions

Bortezomib DRUG

Also known as: Velcade

BD induction followed by ASCT

dexamethasone DRUG

Given orally

BD induction followed by ASCT

filgrastim BIOLOGICAL

Given subcutaneous

ASCT alone; BD induction followed by ASCT

autologous hematopoietic stem cell transplantation (ASCT) PROCEDURE

Given on day 0

ASCT alone; BD induction followed by ASCT

Melphalan DRUG

ASCT alone; BD induction followed by ASCT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Nanjing University School of Medicine: lead

Study Sites (1)

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

Nanjing, Jiangsu, 210002, China

Location

Related Publications (1)

• 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.

  PMID: 24386911 DERIVED

MeSH Terms

Conditions

Amyloidosis; Immunoglobulin Light-chain Amyloidosis

Interventions

Bortezomib; Dexamethasone; Filgrastim; Melphalan

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Study Officials

• Zhihong Liu, MD

  Jinling Hospital, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 15, 2013
• First Posted: November 29, 2013
• Study Start: December 1, 2007
• Primary Completion: June 1, 2013
• Study Completion: August 1, 2013
• Last Updated: November 29, 2013

Record last verified: 2013-11

Locations

CN (1)