Trial Outcomes & Findings for Bortezomib and Dexamethasone Followed by High-Dose Melphalan and Stem Cell Transplantation for Primary (AL) Amyloidosis (NCT NCT01083316)

Last Updated: 2020-09-25

Results Overview

Complete response: Normal serum free light chain ratio and Negative serum and urine immunofixation electrophoresis Very good partial response: Difference in serum free light chains less than 40 mg/L Partial Response: \>50% Reduction in the difference in serum free light chains

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

One year

Results posted on

2020-09-25

Participant Flow

Participant milestones

Participant milestones
Measure	Bortezomib and Dexamethasone Induction: Bortezomib (Velcade) 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1 Bortezomib (Velcade) and Dexamethasone: Induction: Velcade 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1
Overall Study STARTED	35
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Bortezomib and Dexamethasone Induction: Bortezomib (Velcade) 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1 Bortezomib (Velcade) and Dexamethasone: Induction: Velcade 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1
Overall Study Adverse Event	2
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Bortezomib and Dexamethasone Followed by High-Dose Melphalan and Stem Cell Transplantation for Primary (AL) Amyloidosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bortezomib and Dexamethasone n=35 Participants Induction: Bortezomib (Velcade) 1.3 mg/m2/dose intravenous (IV) Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1 Bortezomib (Velcade) and Dexamethasone: Induction: Velcade 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	30 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: One year

Outcome measures

Outcome measures
Measure	Bortezomib and Dexamethasone n=26 Participants Induction: Bortezomib (Velcade) 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1 Bortezomib (Velcade) and Dexamethasone: Induction: Velcade 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1
Number of Participants With Disease Response	20 Participants

PRIMARY outcome

Timeframe: 100 days

Outcome measures

Outcome measures
Measure	Bortezomib and Dexamethasone n=30 Participants Induction: Bortezomib (Velcade) 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1 Bortezomib (Velcade) and Dexamethasone: Induction: Velcade 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1
Number of Participants Surviving at 100 Days Post Transplant	27 Participants

PRIMARY outcome

Timeframe: 2 months

Outcome measures

Outcome measures
Measure	Bortezomib and Dexamethasone n=35 Participants Induction: Bortezomib (Velcade) 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1 Bortezomib (Velcade) and Dexamethasone: Induction: Velcade 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1
Number of Participants Proceeding to Transplant Following Induction	30 Participants

SECONDARY outcome

Timeframe: 5 years

Population: number of patients that completed at least one cycle of induction therapy

Outcome measures

Outcome measures
Measure	Bortezomib and Dexamethasone n=35 Participants Induction: Bortezomib (Velcade) 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1 Bortezomib (Velcade) and Dexamethasone: Induction: Velcade 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1
Number of Participants Surviving at 5 Years	29 Participants

Adverse Events

Bortezomib and Dexamethasone

Serious events: 35 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bortezomib and Dexamethasone n=35 participants at risk Induction: Bortezomib (Velcade) 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1 Bortezomib (Velcade) and Dexamethasone: Induction: Velcade 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1
Immune system disorders autograft versus host disease	5.7% 2/35 • Number of events 2 • 100 days
Blood and lymphatic system disorders neutropenic fever	20.0% 7/35 • Number of events 7 • 100 days
General disorders fever	20.0% 7/35 • 100 days
Renal and urinary disorders Acute kidney failure	8.6% 3/35 • Number of events 3 • 100 days
Respiratory, thoracic and mediastinal disorders Adult Respiratory Distress Syndrome	2.9% 1/35 • Number of events 1 • 100 days
Cardiac disorders cardiac arrest	2.9% 1/35 • Number of events 1 • 100 days
Investigations creatinine increased	2.9% 1/35 • Number of events 1 • 100 days
Gastrointestinal disorders diarrhea	42.9% 15/35 • Number of events 15 • 100 days
Blood and lymphatic system disorders Epstein Barr Virus-related Polymorphous Post Transplant Lymphoproliferative disorder	2.9% 1/35 • Number of events 1 • 100 days
Respiratory, thoracic and mediastinal disorders epistaxis	2.9% 1/35 • Number of events 1 • 100 days
General disorders fatigue	51.4% 18/35 • Number of events 18 • 100 days
Gastrointestinal disorders gastrointestinal bleed	2.9% 1/35 • Number of events 1 • 100 days
Gastrointestinal disorders hemorrhoidal hemmorhage	2.9% 1/35 • Number of events 1 • 100 days
Infections and infestations invasive aspirgillosis	2.9% 1/35 • Number of events 1 • 100 days
General disorders multiorgan failure	2.9% 1/35 • Number of events 1 • 100 days
General disorders nausea	17.1% 6/35 • Number of events 6 • 100 days
Infections and infestations sepsis	11.4% 4/35 • Number of events 4 • 100 days
Nervous system disorders syncope	22.9% 8/35 • Number of events 9 • 100 days
Blood and lymphatic system disorders thrombocytopenia	2.9% 1/35 • Number of events 1 • 100 days
Infections and infestations stomatitis	2.9% 1/35 • Number of events 1 • 100 days
Skin and subcutaneous tissue disorders skin rash	8.6% 3/35 • Number of events 3 • 100 days
Vascular disorders hypotension	31.4% 11/35 • Number of events 11 • 100 days
Nervous system disorders Dizziness	5.7% 2/35 • Number of events 2 • 100 days

Other adverse events

Other adverse events
Measure	Bortezomib and Dexamethasone n=35 participants at risk Induction: Bortezomib (Velcade) 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1 Bortezomib (Velcade) and Dexamethasone: Induction: Velcade 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1
Investigations alkaline phosphatase elevated	11.4% 4/35 • Number of events 4 • 100 days
Blood and lymphatic system disorders drug rash	8.6% 3/35 • Number of events 3 • 100 days
Ear and labyrinth disorders tinnitus	5.7% 2/35 • Number of events 2 • 100 days
Gastrointestinal disorders nausea	42.9% 15/35 • Number of events 15 • 100 days
Gastrointestinal disorders diarrhea	40.0% 14/35 • Number of events 14 • 100 days
Endocrine disorders adrenal insufficiency	11.4% 4/35 • Number of events 4 • 100 days
Gastrointestinal disorders constipation	37.1% 13/35 • Number of events 13 • 100 days
Gastrointestinal disorders anorexia	14.3% 5/35 • Number of events 5 • 100 days
Gastrointestinal disorders abdominal distension	11.4% 4/35 • Number of events 4 • 100 days
Vascular disorders hypotension	22.9% 8/35 • Number of events 8 • 100 days
Skin and subcutaneous tissue disorders alopecia	40.0% 14/35 • Number of events 14 • 100 days
Skin and subcutaneous tissue disorders rash	20.0% 7/35 • Number of events 7 • 100 days
Respiratory, thoracic and mediastinal disorders dyspnea	28.6% 10/35 • Number of events 10 • 100 days
Cardiac disorders sinus tachycardia	45.7% 16/35 • Number of events 16 • 100 days
Musculoskeletal and connective tissue disorders muscle weakness	14.3% 5/35 • Number of events 5 • 100 days
Nervous system disorders dizziness	11.4% 4/35 • Number of events 6 • 100 days
Nervous system disorders anxiety	20.0% 7/35 • Number of events 12 • 100 days
Eye disorders Blurred vision	20.0% 7/35 • Number of events 7 • 100 days
Gastrointestinal disorders Abdominal pain	8.6% 3/35 • Number of events 3 • 100 days
Musculoskeletal and connective tissue disorders Bone pain	34.3% 12/35 • Number of events 14 • 100 days
Respiratory, thoracic and mediastinal disorders cough	17.1% 6/35 • Number of events 7 • 100 days
General disorders peripheral edema	14.3% 5/35 • Number of events 5 • 100 days
Blood and lymphatic system disorders petechiae	11.4% 4/35 • Number of events 4 • 100 days
Gastrointestinal disorders oral mucositis	8.6% 3/35 • Number of events 3 • 100 days

Additional Information

Vaishali Sanchorawala

Boston Medical Center

Phone: 6176386521

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place