CompletedNCT00784823Mel-VelUpdated Aug 11, 2022Results posted

Study Combining Bortezomib With High Dose Melphalan to Treat Multiple Myeloma

A Phase 1/2 interventional study of Bortezomib 1 mg/m2 and Bortezomib 1.3 mg/m2 in Multiple Myeloma, sponsored by Hackensack Meridian Health. Completed at 1 site in United States. Open to participants aged 18 Years to 76 Years. Per ClinicalTrials.gov, last updated 2022-08-11.

Sponsored by Hackensack Meridian Health · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 32
Allocation: Non-randomized
Ages: 18 Years to 76 Years
Sex: All

Study summary

The purpose of this study is to determine the tolerance and potential efficacy of combining dose intense melphalan with escalating doses of bortezomib in patients with multiple myeloma undergoing autologous stem cell transplantation.

Read the detailed description

Multiple myeloma is the second most common hematological malignancy that has affected approximately 40,000 Americans.Conventional chemotherapy has achieved limited control of this disease but studies have reported improved response rates for patients who are treated with dose-intense therapy and autologous hematopoietic stem cell transplantation. This Phase I/II study will investigate the potential of combination therapy of dose-intense melphalan with escalating doses of bortezomib.

Conditions studied

Multiple Myeloma

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In context

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's enrollment of 32 is below the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Browse Multiple Myeloma studies →

Lead sponsor

Hackensack Meridian Health is the lead sponsor of 111 studies on the registry; 28 are open to participants now.

Of its 16 completed or terminated interventional studies of FDA-regulated products, 11 (69%) have results posted.

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

Who can participate

Ages eligible: 18 Years to 76 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

A confirmed diagnosis of multiple myeloma
Show progression of disease after a previous cycle of dose-intense melphalan, or less than 25% decrease in paraprotein measured at 8 weeks after a prior cycle of dose-intense melphalan
- May have received intervening therapies for disease progression after dose-intense melphalan and enrollment in this protocol
Age:18yrs-76yrs at time of melphalan administration
Gender: There is no gender restriction
Availability of >2x10\^6 autologous peripheral blood CD34+ cells/kg or a syngeneic donor meeting eligibility criteria for syngeneic donation
- Syngeneic transplantation is preferred
- For patients enrolled in the phase I part of this study, >1x10\^6 autologous or syngeneic peripheral blood CD34+ cells/kg remaining in storage as "backup" in case of engraftment failure
Recovery from complications of salvage therapy, if administered -

Exclusion criteria

Exclusion Criteria:

Diagnosis other than multiple myeloma
Chemotherapy or radiotherapy within 28 days of initiating treatment in this study
Prior dose-intense therapy within 56 days of initiating treatment in this study
Uncontrolled bacterial,viral,fungal or parasitic infections
Uncontrolled CNS metastases
Known amyloid deposition in heart
Organ dysfunction
- LVEF\<40% or cardiac failure not responsive to therapy
- FVC,FEV1,or DLCO\<50% of predicted and/or receiving supplementary continuous oxygen
- Evidence of hepatic synthetic dysfunction, or total bilirubin>2x or AST>3x ULN
- Measured creatinine clearance \<20ml/min
- Sensory peripheral neuropathy grade 4
Karnofsky score\<70% unless a result of bone disease directly caused by myeloma
Life expectancy limited by another co-morbid illness
History of another malignancy in remission \<2yrs (other than basal cell carcinoma)
Pregnant (women)or unwilling to use acceptable birth control methods (men or women) for twelve months after treatment
Documented hypersensitivity to melphalan or bortezomib or any components of the formulation
Patients unable or unwilling to provide consent

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 32 participants (actual)

Study arms

Experimental
Phase I Cohort - Bortezomib 1 mg/m2
Bortezomib at 1 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
Drug: Bortezomib 1 mg/m2 · Drug: Melphalan
Experimental
Phase I Cohort - Bortezomib 1.3 mg/m2
Bortezomib at 1.3 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
Drug: Bortezomib 1.3 mg/m2 · Drug: Melphalan
Experimental
Phase I Cohort - Bortezomib 1.6 mg/m2
Bortezomib at 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
Drug: Bortezomib 1.6 mg/m2 · Drug: Melphalan
Experimental
Phase II Cohort
Bortezomib at 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
Drug: Bortezomib 1.6 mg/m2 · Drug: Melphalan

Interventions

DrugBortezomib 1 mg/m2
* Bortezomib is administered by rapid I.V. push (over 3-5 seconds) via a central or peripheral vein into a flowing saline line * Bortezomib will be administered any time on day -4 and 24 hrs after the start of the melphalan infusion on day -1 * Dosing will be based on actual body weight Patient weight must be measured within seven days of the start of the treatment regimen
Also known as: Velcade
DrugBortezomib 1.3 mg/m2
* Bortezomib is administered by rapid I.V. push (over 3-5 seconds) via a central or peripheral vein into a flowing saline line * Bortezomib will be administered any time on day -4 and 24 hrs after the start of the melphalan infusion on day -1 * Dosing will be based on actual body weight Patient weight must be measured within seven days of the start of the treatment regimen
Also known as: Velcade
DrugBortezomib 1.6 mg/m2
* Bortezomib is administered by rapid I.V. push (over 3-5 seconds) via a central or peripheral vein into a flowing saline line * Bortezomib will be administered any time on day -4 and 24 hrs after the start of the melphalan infusion on day -1 * Dosing will be based on actual body weight Patient weight must be measured within seven days of the start of the treatment regimen
Also known as: Velcade
DrugMelphalan
* Melphalan is administered by rapid intravenous infusion via a central or peripheral vein over one hour * Melphalan will be dissolved with 10 ml of diluent to a concentration of 5 mg/mL which is then immediately diluted in 0.9% normal saline to a concentration NOT exceeding 0.45 mg/mL prior to administration * The final dilution of melphalan is physically and chemically stable for 60 minutes and therefore will be administered within that time period * Melphalan will be given as a single dose (not split over 2 or more days) * Dosing will be based body surface area calculated using actual body weight
Also known as: Alkeran

What researchers measure

Primary outcomes

The Maximum Tolerated Dose of Bortezomib (MTD)
The Maximum Tolerated Dose of Bortezomib (MTD) Will be Defined as the Dose Level Prior to That Resulting in Two Out of Six Patients Experiencing a DLT
Time frame: During dosing of Bortezomib on Day -4 to Day -1 of ASCT

Results

Posted Aug 11, 2022

Limitations and caveats

The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.

Participant flow

Participant flow — Overall Study
Milestone	Phase I Cohort - Bortezomib Dose 1 mg/m2	Phase I Cohort - Bortezomib 1.3 mg/m2	Phase I Cohort - Bortezomib 1.6 mg/m2	Phase II Cohort
Started	6	3	3	20
Completed	6	3	3	20
Not completed	0	0	0	0

Outcome measures

PrimaryThe Maximum Tolerated Dose of Bortezomib (MTD)

The Maximum Tolerated Dose of Bortezomib (MTD) Will be Defined as the Dose Level Prior to That Resulting in Two Out of Six Patients Experiencing a DLT

Time frame:: During dosing of Bortezomib on Day -4 to Day -1 of ASCT
Reported as:: Number · mg/m2 of bortezomib

The Maximum Tolerated Dose of Bortezomib (MTD)
mg/m2 of bortezomib	Combined Dose Intense Melphalan With Bortezomib (MTD)
The Maximum Tolerated Dose of Bortezomib (MTD)	1.6

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Phase I Cohort	—	6/12 (50%)	12/12 (100%)
Phase II Cohort	—	6/20 (30%)	20/20 (100%)

Most frequent serious events

Most frequent serious events
Event	Phase I Cohort	Phase II Cohort
Engraftment SyndromeBlood and lymphatic system disorders	2/12	0/20
DeathGeneral disorders	0/12	2/20
ICU Admission For Respiratory DistressRespiratory, thoracic and mediastinal disorders	1/12	2/20
SeizureNervous system disorders	1/12	0/20
DiarrheaGastrointestinal disorders	1/12	0/20
Neutropenic FeverBlood and lymphatic system disorders	1/12	0/20
Guillain-Barre SyndromeImmune system disorders	0/12	1/20
Pulmonary EmbolusRespiratory, thoracic and mediastinal disorders	0/12	1/20

Most frequent other events

Showing 10 of 32

Most frequent other events
Event	Phase I Cohort	Phase II Cohort
NauseaGastrointestinal disorders	5/12	6/20
DiarrheaGastrointestinal disorders	4/12	1/20
AnorexiaGastrointestinal disorders	4/12	3/20
MucositisGastrointestinal disorders	4/12	4/20
NeuropathyNervous system disorders	3/12	2/20
FeverInfections and infestations	3/12	2/20
Neutropenic FeverInfections and infestations	3/12	5/20
Shorness of BreathRespiratory, thoracic and mediastinal disorders	1/12	4/20
Gram-positive bacteremiaInfections and infestations	1/12	3/20
VomitingGastrointestinal disorders	1/12	2/20

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Phase I Cohort - Bortezomib Dose 1 mg/m2	Phase I Cohort - Bortezomib 1.3 mg/m2	Phase I Cohort - Bortezomib 1.6 mg/m2	Phase II Cohort	Total
Median	57 (50 to 65)	63 (55 to 65)	58 (49 to 61)	57 (52 to 71)	57 (49 to 71)

Sex: Female, Male
Sex: Female, Male(Participants)	Phase I Cohort - Bortezomib Dose 1 mg/m2	Phase I Cohort - Bortezomib 1.3 mg/m2	Phase I Cohort - Bortezomib 1.6 mg/m2	Phase II Cohort	Total
Female	5	2	1	9	17
Male	1	1	2	11	15

Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)	Phase I Cohort - Bortezomib Dose 1 mg/m2	Phase I Cohort - Bortezomib 1.3 mg/m2	Phase I Cohort - Bortezomib 1.6 mg/m2	Phase II Cohort	Total
Count of participants	—	—	—	—	0

Region of Enrollment
Region of Enrollment(participants)	Phase I Cohort - Bortezomib Dose 1 mg/m2	Phase I Cohort - Bortezomib 1.3 mg/m2	Phase I Cohort - Bortezomib 1.6 mg/m2	Phase II Cohort	Total
United States	6	3	3	20	32

Study locations

1 site

Hackensack University Medical Center
Hackensack, New Jersey 07601, United States

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 11, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00784823
Lead sponsor: Hackensack Meridian Health
Responsible party: Sponsor
First posted: Nov 4, 2008
Start date: Jan 2007
Primary completion: Dec 2013
Completion: Dec 2013
Results posted: Aug 11, 2022
Last update: Aug 11, 2022

Study contacts

Scott D Rowley, MD

principal investigator · Director-Blood and Marrow Transplantation Program

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2022. You cannot join it, but the record below documents what was studied.

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