Melphalan+Bortezomib as a Conditioning Regimen for Autologous and Allogeneic Stem Cell Transplants in Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Bortezomib; Melphalan; Autologous Stem Cell Transplant; Fludarabine; Allogeneic Stem Cell Transplant
Intervention description: AUTOLOGOUS ARM: Day -3 bortezomib (1.3 mg/m^2) as an intravenous push over 3 to 5 seconds (follows Melphalan infusion). ALLOGENEIC ARM: Day -3 bortezomib (1.3 mg/m^2) as an intravenous push over 3 to 5 seconds (follows fludarabine and melphalan infusion).; AUTOLOGOUS ARM: Day -4 and Day -3 Melphalan 100 mg/m^2/day IV over 30 minutes. ALLOGENEIC ARM: Day -4, Day -3 Melphalan 70 mg/m^2/day IV over 30 minutes.; Autologous Stem Cell Transplant: Autologous Peripheral Blood Stem Cell Rescue. Stem cell mobilization with granulocyte colony-stimulating factor (GCSF) at a dose of 10 μg/kg/day as per institutional standards. CD34+ peripheral blood stem cells will be collected following the administration of G-CSF as per institutional standards. Day 0 Infusion of autologous stem cells.; Days -6,-5,-4,-3 Fludarabine 30 mg/m^2/day IV; Allogeneic Stem Cell Transplant: Allogeneic Peripheral Blood Stem Cell Rescue. Day 0 Infusion of allogeneic peripheral blood stem cells. For the allogeneic matched-related donors peripheral blood stem cells will be harvested with GCSF mobilization and infused fresh to the recipients. Allogeneic donor stem cells may also be cryopreserved if they cannot be infused fresh.
Intervention MeSH terms: Fludarabine; Bortezomib; Melphalan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 124.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: multiple myeloma; myeloma; myeloma proteins; autologous; allogeneic; G-CSR; granulocyte colony-stimulating factor; stem cell transplant; stem cell; stem cell mobilization

Summary:

      The purpose of this study is to evaluate the effectiveness of Bortezomib when added to
      standard chemotherapy medicine(s) for treatment of Multiple Myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

        Multiple Myeloma Criteria(International Uniform Response Criteria for Multiple Myeloma)

          -  Patients with responsive disease after any line of induction therapy

          -  A complete response

          -  A very good partial response

          -  A partial response

          -  Patients greater than or equal to 18 years of age are eligible. There is upper age
             limit of 60 years for allogeneic transplants.

          -  Patients must have a histologically confirmed diagnosis.

          -  All patients should have a life expectancy of at least 12 weeks.

          -  Patients must have undergone a complete psychosocial evaluation and have been
             considered capable of compliance.

          -  Meet the following criteria for allogeneic hematopoietic cell transplant:

          -  Must have an identified donor match defined as: HLA-A, HLA-B, HLA- C, DRB1 8/8 allele
             matched sibling, family member, or unrelated donor. [7/8 would go on separate
             mismatched trials] and be < 60 years of age.

          -  Calculated hematopoietic cell transplantation-specific comorbidity index (HCT-CI) <3

        Exclusion Criteria:

          -  Patients who do not achieve at least a partial response (PR) by the criteria mentioned
             above with induction therapy.

          -  Patient has a platelet count of <30 x 10^9/L within 14 days before enrollment.

          -  Patient has >/= Grade 2 peripheral neuropathy within 30 days before enrollment.

          -  Patient has an absolute neutrophil count of <1.0 x 10^9/L within 30 days before
             enrollment.

          -  Myocardial infarction within 6 months prior to enrollment or has New York Hospital
             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 in order for the subject to be considered eligible. Left ventricular ejection
             fraction (LVEF) by multiple gated acquisition (MUGA) scan < 40%.

          -  Patient has hypersensitivity to bortezomib, boron or mannitol.

          -  Female subject is pregnant or breast-feeding. Confirmation that the subject is not
             pregnant must be established by a negative serum beta-human chorionic gonadotropin
             (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not
             required for post-menopausal or surgically sterilized women.

          -  Patient has received other investigational drugs with 30 days before enrollment

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.

          -  Patients with a diffusing capacity of lung for carbon monoxide (DLCO) less than 50%
             (adjusted) of normal or with symptomatic obstructive or restrictive lung disease are
             ineligible.

          -  Patients with a total bilirubin greater than 2.0 mg/dL excluding Gilbert's syndrome
             and serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate
             transaminase (SGPT) greater than two and a half times normal (unless due to primary
             malignancy), or a history of severe hepatic dysfunction are ineligible.

          -  Calculated creatinine clearance </= 30 ml/min within 30 days before enrollment

          -  Patients with active infections are ineligible.

          -  Patients who are HIV positive are ineligible.

          -  Patients with active leptomeningeal involvement are ineligible. Patients with a
             history of previous cerebrospinal fluid (CSF) tumor involvement without symptoms or
             signs are eligible provided the CSF is now free of disease on lumbar puncture, and MRI
             of the brain shows no tumor involvement. Patients with severe symptomatic central
             nervous system (CNS) disease of any etiology are ineligible.

          -  Patients with uncontrolled insulin-dependent diabetes mellitus defined as a random
             glucose level of > 400 in the 30 days prior to initiation of study therapy; or
             uncompensated major thyroid or adrenal dysfunction are ineligible.

          -  Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of >/=
             2(Karnofsky < 50%) are ineligible.

          -  Patients with an ECOG performance status of 2 to 3(Karnofsky 30-50%), secondary to
             bone pain, may be enrolled.

          -  Patients with an ECOG performance status of 2 to 3(Karnofsky 30-50%), secondary to a
             potentially reversible disease-related problem, may be enrolled.

          -  Patients with any previous malignancy other than non-melanoma skin cancer are
             ineligible, unless the patient is without evidence of disease >/= 5 years after the
             treatment for the cancer was completed.