Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma (Flu-Mel-Vel)
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fludarabine monophosphate, melphalan, Bortezomib
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Transplant
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of multiple myeloma
- Have a suitable related or unrelated donor
- Age ≥18 but <70 yrs
- KPS of ≥70%
- Recovery from complications of previous therapies
Exclusion Criteria:
- Diagnosis other than multiple myeloma
- Chemotherapy or radiotherapy within 21 days of initiating treatment in this study
- Prior dose-intense therapy requiring HSC support 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 <20 ml/min
- Sensory peripheral neuropathy grade 4 within 14 days of enrollment
- Karnofsky score <70% unless a result of bone disease directly caused by myeloma
- Life expectancy limited by another co-morbid illness
- Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
- Female subject is pregnant or breast-feeding (women) or unwilling to use acceptable birth control methods (men or women) for twelve months after treatment. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Documented hypersensitivity to fludarabine or melphalan or to bortezomib, boron or mannitol or any components of the formulation
- Patients unable or unwilling to provide consent
- Patient has a sustained platelet count of <30 x 10 9/L within 14 days before enrollment
- Patient has a sustained absolute neutrophil count of <1.0 x10 9/L within 14 days before enrollment
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant
- Patient has received other investigational drugs with 14 days before enrollment
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Sites / Locations
- John Theurer Cancer Center at Hackensack University Medical Center
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Fludarabine, Melphalan, Bortezomib
Arm Description
Outcomes
Primary Outcome Measures
Progression Free Survival
The main primary endpoint of this study is two-year progression free survival. Patients are considered a failure with respect to PFS if they die or experience disease progression or relapse. The time to this event is the time from transplantation to relapse/progression, initiation of non-protocol anti-myeloma therapy, or death from any cause. Subjects alive without confirmed disease progression will be censored at the time of last disease evaluation. Deaths without progression are treated as failures no matter when they occur.
Secondary Outcome Measures
Overall Survival (OS)
Overall survival (OS): Defined as time from the first dose of administration to death from any cause
Overall Response Rate
Overall response rate: Defined as the composite endpoint of response to treatment which includes Complete Response (CR), Partial Response (PR), stable disease (SD) as defined in International Response Criteria.
International Myeloma Working Group Response Criteria for Multiple Myeloma:
CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow PR: > 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to < 200 mg/24 h SD: Not meeting criteria for CR, VGPR, PR, or progressive disease
Full Information
NCT ID
NCT01453101
First Posted
October 13, 2011
Last Updated
April 29, 2022
Sponsor
Hackensack Meridian Health
1. Study Identification
Unique Protocol Identification Number
NCT01453101
Brief Title
Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma
Acronym
Flu-Mel-Vel
Official Title
A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma Using a Conditioning Regimen of Fludarabine, Melphalan, and Bortezomib
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
June 9, 2010 (Actual)
Primary Completion Date
June 11, 2020 (Actual)
Study Completion Date
June 11, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hackensack Meridian Health
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The hypothesis for this study is that the regimen consisting of fludarabine, melphalan and bortezomib improves the progression free survival and the response rate compared to historical controls of fludarabine and melphalan alone.
Detailed Description
Multiple myeloma is the second most prevalent blood cancer (10%) after non-hodgkin's lymphoma. It represents approximately 1% of all cancers and 2% of all cancer deaths. Although the peak age of onset of multiple myeloma is 70 years of age, recent statistics indicate both increasing incidence and earlier age of onset.
The historical control 2-year progression-free survival (PFS) is assumed to be 35%. The proposed therapy of fludarabine, melphalan and bortezomib is expected to improve the PFS by 20%.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, Transplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
54 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fludarabine, Melphalan, Bortezomib
Arm Type
Other
Intervention Type
Drug
Intervention Name(s)
Fludarabine monophosphate, melphalan, Bortezomib
Other Intervention Name(s)
Fludara, Phenylalanine Mustard, Velcade
Intervention Description
Fludarabine will be administered at a dose of 30/mg/m2 IV daily for 4 days starting on transplant day -5.
Melphalan will be administered at a dose of 140 mg/m2 on transplant day-2
Bortezomib will be administered by rapid IV push at a dose of 1.6mg/m2 on days-4 and -1. The bortezomib should be given at least 20 hours after the melphalan.
Primary Outcome Measure Information:
Title
Progression Free Survival
Description
The main primary endpoint of this study is two-year progression free survival. Patients are considered a failure with respect to PFS if they die or experience disease progression or relapse. The time to this event is the time from transplantation to relapse/progression, initiation of non-protocol anti-myeloma therapy, or death from any cause. Subjects alive without confirmed disease progression will be censored at the time of last disease evaluation. Deaths without progression are treated as failures no matter when they occur.
Time Frame
Subjects will be followed for progression-free survival for at least 36 months
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Overall survival (OS): Defined as time from the first dose of administration to death from any cause
Time Frame
Up to 3 years
Title
Overall Response Rate
Description
Overall response rate: Defined as the composite endpoint of response to treatment which includes Complete Response (CR), Partial Response (PR), stable disease (SD) as defined in International Response Criteria.
International Myeloma Working Group Response Criteria for Multiple Myeloma:
CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow PR: > 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to < 200 mg/24 h SD: Not meeting criteria for CR, VGPR, PR, or progressive disease
Time Frame
Up to 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of multiple myeloma
Have a suitable related or unrelated donor
Age ≥18 but <70 yrs
KPS of ≥70%
Recovery from complications of previous therapies
Exclusion Criteria:
Diagnosis other than multiple myeloma
Chemotherapy or radiotherapy within 21 days of initiating treatment in this study
Prior dose-intense therapy requiring HSC support 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 <20 ml/min
Sensory peripheral neuropathy grade 4 within 14 days of enrollment
Karnofsky score <70% unless a result of bone disease directly caused by myeloma
Life expectancy limited by another co-morbid illness
Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
Female subject is pregnant or breast-feeding (women) or unwilling to use acceptable birth control methods (men or women) for twelve months after treatment. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
Documented hypersensitivity to fludarabine or melphalan or to bortezomib, boron or mannitol or any components of the formulation
Patients unable or unwilling to provide consent
Patient has a sustained platelet count of <30 x 10 9/L within 14 days before enrollment
Patient has a sustained absolute neutrophil count of <1.0 x10 9/L within 14 days before enrollment
Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant
Patient has received other investigational drugs with 14 days before enrollment
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Facility Information:
Facility Name
John Theurer Cancer Center at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma
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