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

• ClinicalTrials.gov Identifier: NCT01453101
• Recruitment Status: Completed
• First Posted: October 17, 2011
• Results First Posted: May 25, 2022
• Last Update Posted: May 25, 2022
• Sponsor: Hackensack Meridian Health
• Information provided by (Responsible Party): Hackensack Meridian Health

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 (Clinical Trial)
• 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: June 9, 2010
• Actual Primary Completion Date: June 11, 2020
• Actual Study Completion Date: June 11, 2020

Arms and Interventions

Arm

Intervention/treatment

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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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

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

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

Contacts and Locations

Locations

United States, New Jersey

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

Sponsors and Collaborators

Hackensack Meridian Health

  Study Documents (Full-Text)

Documents provided by Hackensack Meridian Health:

Study Protocol and Statistical Analysis Plan  [PDF] November 8, 2019

More Information

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

Keywords provided by Hackensack Meridian Health:

Multiple Myeloma; Transplant

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Fludarabine; Fludarabine phosphate; Bortezomib; Melphalan; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists