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Clinical Trial Results:
A multicenter, phase II study of bortezomib and dexamethasone as induction treatment followed by high dose melphalan (HDM) and autologous stem cell transplantation (SCT) in patients with de novo amyloid light chain (AL) amyloidosis.

Summary
EudraCT number	2010-021445-42
Trial protocol	NL BE DE
Global end of trial date	29 Jan 2021

Results information
Results version number	v1(current)
This version publication date	04 Sep 2022
First version publication date	04 Sep 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

HO104

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

HOVON

Sponsor organisation address

De Boelelaan 1117, Amsterdam, Netherlands,

Public contact

HOVON Data Center, HOVON, 31 (0)107041560, hdc@erasmusmc.nl

Scientific contact

HOVON Data Center, HOVON, 31 (0)107041560, hdc@erasmusmc.nl

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

14 Jul 2017

Is this the analysis of the primary completion data?

Yes

Primary completion date

16 Jun 2016

Global end of trial reached?

Yes

Global end of trial date

29 Jan 2021

Was the trial ended prematurely?

Main objective of the trial

To determine the efficacy of bortezomib plus dexamethasone followed by HDM and auto-SCT in patients with newly diagnosed AL amyloidosis who are 18-70 years inclusive.

Protection of trial subjects

Monitoring and Insurance

Background therapy

Evidence for comparator

Actual start date of recruitment

12 Jan 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 45

Country: Number of subjects enrolled

Belgium: 4

Country: Number of subjects enrolled

Germany: 8

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

All subjects gave written informed consent and were screened according to the inclusion- and exclusion criteria

Period 1 title

Overall period

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Experimental group

Arm description

Arm type

Experimental

Investigational medicinal product name

Bortezomib

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Patients will be treated with 4 cycles of bortezomib and dexamethasone (q 3 weeks). The recommended starting dose of bortezomib is 1.3 mg/m2 and it is given subcutaneously in the hospital on an outpatient basis.

Number of subjects in period 1	Experimental group
Started	57
Completed	38
Not completed	19
Consent withdrawn by subject	1
not eligible for ASCT or other causes	9
Adverse events	5
Lack of efficacy	4

Baseline characteristics

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Reporting group title

Overall period

Reporting group description

Reporting group values	Overall period	Total
Number of subjects	57	57
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	0	0
From 65-84 years	0	0
85 years and over	0	0
Adults (18-70 years)	57	57
Age continuous
Units: years
median (full range (min-max))	59 (26 to 70)	-
Gender categorical
Units: Subjects
Female	25	25
Male	32	32

End points

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Reporting group title

Experimental group

Reporting group description

Primary: Primary endpoint

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End point title

Primary endpoint ^[1]

End point description

End point type

Primary

End point timeframe

See publication.

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: see attached chart/documents for results

End point values	Experimental group
Number of subjects analysed	57
Units: Whole	57

Attachments

Statistical data section from publication
List of reported non-SAE's
List of reported SAE's

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse events will be reported from the first study-related procedure until 30 days following the last dose of any drug from the protocol treatment schedule or until the start of subsequent systemic therapy for the disease under study, if earlier.

Adverse event reporting additional description

Adverse events occurring after 30 days should also be reported if considered at least possibly related to the investigational medicinal product by the investigator.

Assessment type

Systematic

Dictionary name

CTCAE

Dictionary version

Reporting group title

Experimental group

Reporting group description

Serious adverse events	Experimental group
Total subjects affected by serious adverse events
subjects affected / exposed	35 / 57 (61.40%)
number of deaths (all causes)	14
number of deaths resulting from adverse events
Vascular disorders
Hypotension
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Orthostatic hypotension
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Symptomatic hypotension
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
General disorders and administration site conditions
Oedema
subjects affected / exposed	2 / 57 (3.51%)
occurrences causally related to treatment / all	2 / 2
deaths causally related to treatment / all	0 / 0
General malaise
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnea/ bronchial hyperreactivity
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Pulmonary bleeding
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Pulmonary embolism
subjects affected / exposed	2 / 57 (3.51%)
occurrences causally related to treatment / all	1 / 2
deaths causally related to treatment / all	0 / 0
Injury, poisoning and procedural complications
Sinusitis
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Cardiac disorders
Cardiac arrest
subjects affected / exposed	2 / 57 (3.51%)
occurrences causally related to treatment / all	2 / 2
deaths causally related to treatment / all	2 / 2
Heart failure
subjects affected / exposed	5 / 57 (8.77%)
occurrences causally related to treatment / all	4 / 6
deaths causally related to treatment / all	0 / 0
Cardiac right ventricular dysfunction
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Complete atrioventricular block
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Myocardial infarction
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Nervous system disorders
Intercranial hemorrhage
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Near syncope
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Poly neuropathy
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Blood and lymphatic system disorders
Thrombopenia
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Gastrointestinal disorders
Colitis
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Diarrhea
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Gastro−intestinal necrosis
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Ischemic colitis
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Pancreatitis
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Hepato−Renal sundrome
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 1
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Acute tubulus necrosis
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Progress. of renal insufficiency
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Renal insufficiency
subjects affected / exposed	2 / 57 (3.51%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Musculoskeletal and connective tissue disorders
Muscle weakness arms and legs
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Infections and infestations
Communitiy aquired pneumonia
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Gastrointestinal infection
subjects affected / exposed	2 / 57 (3.51%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Lung infection
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Pneumonia
subjects affected / exposed	4 / 57 (7.02%)
occurrences causally related to treatment / all	3 / 4
deaths causally related to treatment / all	0 / 0
Pneumosepsis
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Sepsis
subjects affected / exposed	3 / 57 (5.26%)
occurrences causally related to treatment / all	3 / 3
deaths causally related to treatment / all	0 / 0
Viral infection
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	2 / 2
deaths causally related to treatment / all	0 / 0
Fluid overflow
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Fluid retention
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Hypoglycemia
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Hyponatremia
subjects affected / exposed	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Experimental group
Total subjects affected by non serious adverse events
subjects affected / exposed	52 / 57 (91.23%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	2 / 57 (3.51%)
occurrences all number	2
Vascular disorders
Vascular disorders
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	15 / 57 (26.32%)
occurrences all number	20
General disorders and administration site conditions
General disorders and administration site conditions
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	32 / 57 (56.14%)
occurrences all number	53
Immune system disorders
Immune system disorders
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	1 / 57 (1.75%)
occurrences all number	1
Reproductive system and breast disorders
Reproductive system and breast disorders
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	1 / 57 (1.75%)
occurrences all number	1
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	17 / 57 (29.82%)
occurrences all number	20
Psychiatric disorders
Psychiatric disorders
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	12 / 57 (21.05%)
occurrences all number	14
Investigations
Investigations
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	25 / 57 (43.86%)
occurrences all number	50
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	1 / 57 (1.75%)
occurrences all number	1
Cardiac disorders
Cardiac disorders
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	13 / 57 (22.81%)
occurrences all number	21
Nervous system disorders
Nervous system disorders
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	33 / 57 (57.89%)
occurrences all number	63
Blood and lymphatic system disorders
Blood and lymphatic disorders
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	16 / 57 (28.07%)
occurrences all number	24
Eye disorders
Eye disorders
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	5 / 57 (8.77%)
occurrences all number	8
Gastrointestinal disorders
Gastrointestinal disorders
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	33 / 57 (57.89%)
occurrences all number	78
Hepatobiliary disorders
Hepatobiliary disorders
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	2 / 57 (3.51%)
occurrences all number	2
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	12 / 57 (21.05%)
occurrences all number	19
Renal and urinary disorders
Renal and urinary disorders
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	6 / 57 (10.53%)
occurrences all number	8
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	11 / 57 (19.30%)
occurrences all number	11
Infections and infestations
Infections and infestations
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	25 / 57 (43.86%)
occurrences all number	40
Metabolism and nutrition disorders
Metabolism and nutrition disorders
Additional description: All combined, see non-SAE chart for details
subjects affected / exposed	27 / 57 (47.37%)
occurrences all number	63

More information

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Were there any global substantial amendments to the protocol? Yes

20 Dec 2011

AM1: change of administration route bortezomib (s.c. instead of i.v.). New version of protocol, ICF, bortezomib IB and bortezomib labels.

10 Jul 2012

AM2: addition of pre-study ICF, new version of protocol, ICF and bortezomib IB.

10 Jan 2013

AM3: new version of protocol, ICF and bortezomib IB.

27 Mar 2014

AM4: closure of dexa-only arm, new version of protocol, ICF and bortezomib IB

17 Jul 2015

AM5: new version of protocol, ICF and bortezomib IB.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/30923094

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Clinical trials

Clinical Trial Results:
A multicenter, phase II study of bortezomib and dexamethasone as induction treatment followed by high dose melphalan (HDM) and autologous stem cell transplantation (SCT) in patients with de novo amyloid light chain (AL) amyloidosis.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Primary endpoint

Primary: Primary endpoint

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

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Belgium
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Croatia
Cyprus
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Denmark
Estonia
Finland
France
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Greece
Hungary
Iceland
Ireland
Italy
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Outside EU/EEA

Clinical trials

Clinical Trial Results: A multicenter, phase II study of bortezomib and dexamethasone as induction treatment followed by high dose melphalan (HDM) and autologous stem cell transplantation (SCT) in patients with de novo amyloid light chain (AL) amyloidosis.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Primary endpoint

Primary: Primary endpoint

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
A multicenter, phase II study of bortezomib and dexamethasone as induction treatment followed by high dose melphalan (HDM) and autologous stem cell transplantation (SCT) in patients with de novo amyloid light chain (AL) amyloidosis.