Flu-Mel-Vel: Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma

• Sponsor: Hackensack Meridian Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT01453101
• Collaborator: (none)
• Enrollment: 54
• Location: 1
• Arm: 1
• Actual Duration (Months): 120.1
• Patients Per Site Per Month: 0.4

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Fludarabine monophosphate, melphalan, Bortezomib	Phase 2

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%.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma Using a Conditioning Regimen of Fludarabine, Melphalan, and Bortezomib
• Actual Study Start Date: Jun 9, 2010
• Actual Primary Completion Date: Jun 11, 2020
• Actual Study Completion Date: Jun 11, 2020

Arms and Interventions

Arm

Intervention/Treatment

Other: Fludarabine, Melphalan, Bortezomib

Drug: Fludarabine monophosphate, melphalan, Bortezomib; 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.; Other Names: Fludara Phenylalanine Mustard Velcade

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [Subjects will be followed for progression-free survival for at least 36 months]

   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

1. Overall Survival (OS) [Up to 3 years]

   Overall survival (OS): Defined as time from the first dose of administration to death from any cause

2. Overall Response Rate [Up to 3 years]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 69 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601

Sponsors and Collaborators

• Hackensack Meridian Health

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 8, 2019

More Information

Publications

None provided.

• Responsible Party: Hackensack Meridian Health
• ClinicalTrials.gov Identifier: NCT01453101
• Other Study ID Numbers: PRO1261
• First Posted: Oct 17, 2011
• Last Update Posted: May 25, 2022
• Last Verified: Apr 1, 2022

• Keywords provided by Hackensack Meridian Health: Multiple Myeloma; Transplant
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Fludarabine; Fludarabine phosphate; Bortezomib; Melphalan

Study Results

Participant Flow

Arm/Group Title	Fludarabine, Melphalan, Bortezomib
Arm/Group Description	Fludarabine monophosphate, melphalan, Bortezomib: •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.
Period Title: Overall Study
STARTED	54
COMPLETED	54
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Fludarabine, Melphalan, Bortezomib
Arm/Group Description	Fludarabine monophosphate, melphalan, Bortezomib: •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.
Overall Participants	54
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56
Sex: Female, Male (Count of Participants)
Female	19 35.2%
Male	35 64.8%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	54 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fludarabine, Melphalan, Bortezomib
Arm/Group Description	Fludarabine monophosphate, melphalan, Bortezomib: •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.
Measure Participants	54
Median (Full Range) [Months]	16.7

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fludarabine, Melphalan, Bortezomib
Arm/Group Description	Fludarabine monophosphate, melphalan, Bortezomib: •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.
Measure Participants	54
Number [percentage]	42

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fludarabine, Melphalan, Bortezomib
Arm/Group Description	Fludarabine monophosphate, melphalan, Bortezomib: •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.
Measure Participants	54
Count of Participants [Participants]	45 83.3%

Adverse Events

Time Frame	Collected for 3 years post transplant per patient
Arm/Group Title	Fludarabine, Melphalan, Bortezomib
Arm/Group Description	Fludarabine monophosphate, melphalan, Bortezomib: •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.
All Cause Mortality
	Fludarabine, Melphalan, Bortezomib
	Affected / at Risk (%)	# Events
Total	27/54 (50%)
Serious Adverse Events
	Fludarabine, Melphalan, Bortezomib
	Affected / at Risk (%)	# Events
Total	29/54 (53.7%)
Blood and lymphatic system disorders
Hyponatremia	1/54 (1.9%)
Thrombocytopenia	1/54 (1.9%)
Cardiac disorders
Atrial Fibrillation	2/54 (3.7%)
Endocrine disorders
Diabetic Ketoacidosis	1/54 (1.9%)
Eye disorders
Decreased Visual Acuity	1/54 (1.9%)
Gastrointestinal disorders
Rectal Hemmorhage	1/54 (1.9%)
hemorrhoidal rectal bleed	1/54 (1.9%)
Diarrhea	3/54 (5.6%)
Nausea and Vomiting	1/54 (1.9%)
GI Disorder	2/54 (3.7%)
GI Pain	1/54 (1.9%)
Malnutrition	1/54 (1.9%)
General disorders
fever	10/54 (18.5%)
Intractable Migraine	1/54 (1.9%)
Multisystem Failure	3/54 (5.6%)
Progressive Disease	7/54 (13%)
Confusion	2/54 (3.7%)
Fall	1/54 (1.9%)
Immune system disorders
Graft versus Host Disease	9/54 (16.7%)
Infections and infestations
infection/sepsis/URI	29/54 (53.7%)
Abdominal Wall Cellulitis	1/54 (1.9%)
Nervous system disorders
Epidural Tumor	1/54 (1.9%)
Cerebral Edema	1/54 (1.9%)
Renal and urinary disorders
Renal Failure	2/54 (3.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/54 (3.7%)
Pneumonia	4/54 (7.4%)
Respiratory Distress/Fluid Overload	1/54 (1.9%)
Metapneumovirus Infection	3/54 (5.6%)
Shortness of Breath	1/54 (1.9%)
Shortness of Breath	2/54 (3.7%)
Respiratory Syncytial Virus	1/54 (1.9%)
Vascular disorders
Hypertension	1/54 (1.9%)
Hypotension	1/54 (1.9%)
Veno Occlusive Disease	1/54 (1.9%)
Hemolytic Anemia	1/54 (1.9%)
Other (Not Including Serious) Adverse Events
	Fludarabine, Melphalan, Bortezomib
	Affected / at Risk (%)	# Events
Total	0/54 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.