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

A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma Using a Conditioning Regimen of Fludarabine, Melphalan, and Bortezomib

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Fludarabine monophosphate, melphalan, Bortezomib

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 Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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; Velcade; Phenylalanine Mustard

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Subjects will be followed for progression-free survival for at least 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival (OS): Defined as time from the first dose of administration to death from any cause	Up to 3 years
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	Up to 3 years

Collaborators and Investigators

• Sponsor: Hackensack Meridian Health

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2010
• Primary Completion (Actual): June 11, 2020
• Study Completion (Actual): June 11, 2020

Study Registration Dates

• First Submitted: October 13, 2011
• First Submitted That Met QC Criteria: October 14, 2011
• First Posted (Estimate): October 17, 2011

Study Record Updates

• Last Update Posted (Actual): May 25, 2022
• Last Update Submitted That Met QC Criteria: April 29, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Transplant
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan; Bortezomib; Fludarabine; Fludarabine phosphate
• Other Study ID Numbers: PRO1261