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CompletedNCT00298766Updated Jun 25, 2012Results posted

Open-Label Phase 1/2 Study of VELCADE for Injection in Patients With Light-chain (AL)-Amyloidosis

A Phase 1/2 interventional study of VELCADE in Amyloidosis, sponsored by Millennium Pharmaceuticals, Inc.. Completed at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2012-06-25.

Sponsored by Millennium Pharmaceuticals, Inc. · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
70
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
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Study summary

This is a phase 1/2 open-label, dose-escalation study investigating single-agent therapy with VELCADE in patients with previously treated systemic AL-amyloidosis who require further treatment.

02

Conditions studied

  • Amyloidosis

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03

In context

Amyloidosis

491 studies on the registry are indexed under Amyloidosis; 135 are open to participants now.

This study's enrollment of 70 is above the median of 40 across 304 interventional studies indexed under Amyloidosis.

Browse Amyloidosis studies →

Lead sponsor

Millennium Pharmaceuticals, Inc. is the lead sponsor of 173 studies on the registry; none are open to participants now.

Of its 73 completed or terminated interventional studies of FDA-regulated products, 72 (99%) have results posted.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Male or Female 18 y/o and older
  2. Female patients must be practicing an effective method of birth control
  3. Biopsy-proven AL-amyloidosis
  4. Must have been previously treated (failed at least 1 previous treatment) and in the opinion of the physician, patient requires further treatment

Exclusion criteria

Exclusion Criteria:

  1. Hypersensitivity to boron or mannitol
  2. Prior treatment with VELCADE
  3. Patient requires other concomitant chemotherapy, radiotherapy or ancillary therapy considered investigational
  4. Uncontrolled infection
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
70 participants (actual)

Study arms

  • Experimental
    1

    VELCADE

    Drug: VELCADE

Interventions

  • DrugVELCADE

    Once weekly at: 0.7, 1.0, 1.3 or 1.6 mg/m2 Or Twice-weekly at: 0.7, 1.0, or 1.3 mg/m2

    Also known as: Bortezomib

06

What researchers measure

Primary outcomes

  1. Maximum Tolerated Dose

    Maximum Tolerated Dose (MTD) was defined as the highest dose level that has 0/1 out of 6 patients experiences Dose Limited Toxicity (DLT). MTD is defined separately for QW and BIQ dose cohorts. DLT was defined as adverse events occurring during Cycle 1 and: (1) related to VELCADE, (2) Grade 4 thrombocytopenia or neutropenia, (3) Grade 3 or higher nonhematologic toxicity.

    Time frame: 5 weeks in once weekly (QW) dose cohorts and 3 weeks in twice weekly (BIW) dose cohorts

  2. Subjects With Treatment Emergent Adverse Events

    Treatment emergent adverse events observed during outcome measure time frame

    Time frame: from first study-related procedure to 30 days after last dose of study medication

  3. Subjects With Serious Treatment Emergent Adverse Events

    Serious treatment emergent adverse events observed during outcome measure time frame

    Time frame: from first study-related procedure to 30 days after last dose of study medication

  4. Subjects Grade 3/4/5 Treatment Emergent Adverse Events

    Grade 3/4/5 treatment emergent adverse events observed during outcome measure time frame. Grade is determined according to Common Terminology Criteria for Adverse Event (CTCAE) Version 3.0.

    Time frame: from first study-related procedure to 30 days after last dose of study medication

  5. Subjects With Treatment Emergent Adverse Events Leading to Treatment Termination

    Treatment emergent adverse events observed during outcome measure time frame leading to treatment termination

    Time frame: from first study-related procedure to 30 days after last dose of study medication

Secondary outcomes

  1. Best Confirmed Hematologic Responders

    Hematologic response was determined by the investigator per the response criteria for immunoglobulin light chain amyloidosis by Gertz (2005). It include Complete and Partial Responders (CR+PR). CR requires serum and urine negative for a monoclonal protein by immunofixation and free light chain ratio normal. PR requires: 1. reduction in quantitative serum M-protein by 50% if baseline value is at least 0.5 g/dL, 2. if light chain is detected in the urine (with a consistent peak and \>100 mg/ 24 hours), then 50% reduction is required, 3. if free light chain \>10 mg/dL, reduction by 50% is required.

    Time frame: from first dose of study medication to end of study visit

07

Results

Posted Aug 13, 2010

Participant flow

Participant flow — Overall Study
MilestoneSingle Agent VELCADE
Started70
Completed24
Not completed46
Withdrew: Adverse event18
Withdrew: Death2
Withdrew: Withdrawal by subject9
Withdrew: Treatment ongoing4
Withdrew: Progression of amyloid markers4
Withdrew: Deterioration in kps and organ function1
Withdrew: Subjects overall condition deterioration4
Withdrew: Other4

Outcome measures

PrimaryMaximum Tolerated Dose

Maximum Tolerated Dose (MTD) was defined as the highest dose level that has 0/1 out of 6 patients experiences Dose Limited Toxicity (DLT). MTD is defined separately for QW and BIQ dose cohorts. DLT was defined as adverse events occurring during Cycle 1 and: (1) related to VELCADE, (2) Grade 4 thrombocytopenia or neutropenia, (3) Grade 3 or higher nonhematologic toxicity.

Time frame:
5 weeks in once weekly (QW) dose cohorts and 3 weeks in twice weekly (BIW) dose cohorts
Reported as:
Number · participants with DLT
Maximum Tolerated Dose
participants with DLTSingle Agent VELCADE
Maximum Tolerated Dose2
PrimarySubjects With Treatment Emergent Adverse Events

Treatment emergent adverse events observed during outcome measure time frame

Time frame:
from first study-related procedure to 30 days after last dose of study medication
Reported as:
Number · participants
Subjects With Treatment Emergent Adverse Events
participantsSingle Agent VELCADE
Subjects With Treatment Emergent Adverse Events70
SecondaryBest Confirmed Hematologic Responders

Hematologic response was determined by the investigator per the response criteria for immunoglobulin light chain amyloidosis by Gertz (2005). It include Complete and Partial Responders (CR+PR). CR requires serum and urine negative for a monoclonal protein by immunofixation and free light chain ratio normal. PR requires: 1. reduction in quantitative serum M-protein by 50% if baseline value is at least 0.5 g/dL, 2. if light chain is detected in the urine (with a consistent peak and \>100 mg/ 24 hours), then 50% reduction is required, 3. if free light chain \>10 mg/dL, reduction by 50% is required.

Time frame:
from first dose of study medication to end of study visit
Reported as:
Number · participants responded
Best Confirmed Hematologic Responders
participants respondedSingle Agent VELCADE
Best Confirmed Hematologic Responders33
PrimarySubjects With Serious Treatment Emergent Adverse Events

Serious treatment emergent adverse events observed during outcome measure time frame

Time frame:
from first study-related procedure to 30 days after last dose of study medication
Reported as:
Number · participants
Subjects With Serious Treatment Emergent Adverse Events
participantsSingle Agent VELCADE
Subjects With Serious Treatment Emergent Adverse Events25
PrimarySubjects Grade 3/4/5 Treatment Emergent Adverse Events

Grade 3/4/5 treatment emergent adverse events observed during outcome measure time frame. Grade is determined according to Common Terminology Criteria for Adverse Event (CTCAE) Version 3.0.

Time frame:
from first study-related procedure to 30 days after last dose of study medication
Reported as:
Number · participants
Subjects Grade 3/4/5 Treatment Emergent Adverse Events
participantsSingle Agent VELCADE
Subjects Grade 3/4/5 Treatment Emergent Adverse Events43
PrimarySubjects With Treatment Emergent Adverse Events Leading to Treatment Termination

Treatment emergent adverse events observed during outcome measure time frame leading to treatment termination

Time frame:
from first study-related procedure to 30 days after last dose of study medication
Reported as:
Number · participants
Subjects With Treatment Emergent Adverse Events Leading to Treatment Termination
participantsSingle Agent VELCADE
Subjects With Treatment Emergent Adverse Events Leading to Treatment Termination23

Adverse events

Collected over from first study-related procedure to 30 days after last dose of study medication. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Single Agent VELCADE—25/70 (35.7%)70/70 (100%)
Most frequent serious events
Showing 10 of 42
Most frequent serious events
EventSingle Agent VELCADE
PneumoniaInfections and infestations3/70
DiarrhoeaGastrointestinal disorders2/70
VomitingGastrointestinal disorders2/70
Renal failure acuteRenal and urinary disorders2/70
HypotensionVascular disorders2/70
ThrombocytopeniaBlood and lymphatic system disorders1/70
Atrial fibrillationCardiac disorders1/70
Cardiac failure acuteCardiac disorders1/70
Cardiac failure cogestiveCardiac disorders1/70
Restrictive cardiomyopathyCardiac disorders1/70
Most frequent other events
Showing 10 of 58
Most frequent other events
EventSingle Agent VELCADE
DizzinessNervous system disorders21/70
Pain in extremityMusculoskeletal and connective tissue disorders19/70
CoughRespiratory, thoracic and mediastinal disorders19/70
ParaesthesiaNervous system disorders17/70
Oedema peripheralGeneral disorders16/70
HeadacheNervous system disorders16/70
OedemaGeneral disorders15/70
Back painMusculoskeletal and connective tissue disorders13/70
Abdominal distensionGastrointestinal disorders12/70
PyrexiaGeneral disorders12/70

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Single Agent VELCADE
<=18 years0
Between 18 and 65 years43
>=65 years27
Age Continuous
Age Continuous(years)Single Agent VELCADE
Mean61 ± 10.10
Sex: Female, Male
Sex: Female, Male(Participants)Single Agent VELCADE
Female31
Male39
Region of Enrollment
Region of Enrollment(participants)Single Agent VELCADE
United States35
Canada8
France3
Germany11
Italy9
Spain4
08

Study locations

4 sites
  • Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
    Los Angeles, California 90049, United States
  • Winship Cancer Center - Emory Clinic School of Medicine
    Atlanta, Georgia 30322, United States
  • Boston Medical Center
    Boston, Massachusetts 02118, United States
  • MSKCC
    New York, New York 10017, United States
09

References and documents

Publications

  • Reece DE, Hegenbart U, Sanchorawala V, Merlini G, Palladini G, Blade J, Fermand JP, Hassoun H, Heffner L, Kukreti V, Vescio RA, Pei L, Enny C, Esseltine DL, van de Velde H, Cakana A, Comenzo RL. Long-term follow-up from a phase 1/2 study of single-agent bortezomib in relapsed systemic AL amyloidosis. Blood. 2014 Oct 16;124(16):2498-506. doi: 10.1182/blood-2014-04-568329. Epub 2014 Sep 8. PubMed 25202139 ↗
  • Reece DE, Hegenbart U, Sanchorawala V, Merlini G, Palladini G, Blade J, Fermand JP, Hassoun H, Heffner L, Vescio RA, Liu K, Enny C, Esseltine DL, van de Velde H, Cakana A, Comenzo RL. Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study. Blood. 2011 Jul 28;118(4):865-73. doi: 10.1182/blood-2011-02-334227. Epub 2011 May 11. PubMed 21562045 ↗
  • Reece DE, Sanchorawala V, Hegenbart U, Merlini G, Palladini G, Fermand JP, Vescio RA, Liu X, Elsayed YA, Cakana A, Comenzo RL; VELCADE CAN2007 Study Group. Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: results of a phase 1 dose-escalation study. Blood. 2009 Aug 20;114(8):1489-97. doi: 10.1182/blood-2009-02-203398. Epub 2009 Jun 4. PubMed 19498019 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 25, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00298766
Lead sponsor
Millennium Pharmaceuticals, Inc.
Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Responsible party
Sponsor
First posted
Mar 3, 2006
Start date
Jun 2005
Primary completion
Jul 2009
Completion
Sep 2009
Results posted
Aug 13, 2010
Last update
Jun 25, 2012

Study contacts

Medical Monitor
study director · Millennium Pharmaceuticals, Inc.
View the source record on ClinicalTrials.gov ↗

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