Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Fludarabine monophosphate, melphalan, Bortezomib
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.
Intervention MeSH terms: Fludarabine; Fludarabine phosphate; Bortezomib; Melphalan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Maximum age: 69 Years
Healthy volunteers: No
Keywords: Multiple Myeloma; Transplant

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.
    

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