First Autologous Transplant on Minimal Residual Disease Markers in Previously Untreated Myeloma Undergoing Initial Treatment With Velcade
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasm, Residual
Intervention: VELCADE; Lenalidomide; Dexamethasone; DVT prophylaxis; Bisphosphonates; Liposomal doxorubicin; Dexamethasone
Intervention description: 1.3 mg/m2 by IV on days 1, 4, 8, 11 of each cycle; 25 mg by mouth on days 1-4 of each cycle; 20 mg the day before and the day after receiving VELCADE; At least one asprin 81 mg per day. Other option per physician's choice; Zoledronic acid by IB or pamidronate by IV can be used as per standard of care.; 30 mg/m2 on day 4 of each cycle; 40 mg by mouth on days 1-4, 8-11, and 15-18 of cycle 1 and days 1-4 on cycle 2-4
Intervention MeSH terms: Diphosphonates; Dexamethasone; Dexamethasone acetate; Doxorubicin; Liposomal doxorubicin; Lenalidomide; Bortezomib; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to study the MRD status after VELCADE based induction therapy
      (VELCADE, lenalidomide, dexamethasone or VELCADE, liposomal doxorubicin, dexamethasone) in
      patients with previously untreated multiple myeloma and study the impact of HDC and ASCT on
      MRD status post-transplant. Our hypothesis is that MRD-status will continue to increase
      significantly at 3 months post-transplant and will validate that HDC and ASCT needs to be
      performed even when patients have achieved major response after induction therapy with novel
      agents.
    

Eligibility criteria:

        Inclusion Criteria:

        Confirmed Multiple Myeloma as defined below within 120 days of starting cycle 1:

          -  Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy
             proven plasmacytoma

          -  Presence of M protein in serum or urine or both. Conventional M spike, serum free
             light chains, or 24 hour urine study. Non-secretory myeloma is not eligible for this
             study.

          -  In addition patient must have one of the following organ dysfunction criteria

          -  Hypercalcemia

          -  Renal insufficiency

          -  Anemia

          -  Bone disease manifested by lytic lesion or osteoporosis (if osteoporosis is the only
             organ dysfunction criteria then BM should have ≥ 30% plasma cells)

          -  Confirmed Multiple myeloma as defined above within 90 days of starting cycle 1

          -  The following study assessments must be fulfilled and must be obtained with four weeks
             of starting cycle 1

          -  Hemoglobin > 7 g/dL, Platelet count > 75 X 10 to 9th power/L, and Absolute neutrophil
             count > 1 X 10 to 9th power/L

          -  Creatinine <2.5 mg/dL or calculated creatinine clearance > 30 ml/min/1.72 m2

          -  Bilirubin ≤ 1.5 mg/dL X ULN

          -  SGPT (ALT) and SGOT (AST) ≤ 2.5 times the upper limit of normal

          -  Ejection fraction ≥ 45% as measured by a MUGA scan or 2 D echocardiogram

          -  Pulmonary function tests show >60% predicted values for FVC, FEV1, and DLCO FEV1 must
             be > 1 liter.

          -  No prior systemic therapy with the exception of bisphosphonates for MM

          -  Prior glucocorticoid therapy for the treatment of multiple myeloma is not permitted
             EXCEPT if used in conjunction with palliative radiation to prevent vasogenic edema. In
             that case steroids should have been used for less than 7 days. Prior steroid use for
             non-malignant disorders is permitted and should have been restricted to less than the
             equivalent of prednisone 10 mg per day. Prior or concurrent topical or localized
             steroid therapy to treat non-malignant disorders is permitted

          -  Prior palliative and/ or localized radiation therapy is permitted provided at least 4
             weeks have passed from date of last radiation therapy to starting cycle 1.

          -  Patients with prior solitary plasmacytoma treated with radiation therapy with curative
             intent are eligible if the disease has now progressed to active multiple myeloma and
             meeting all eligibility criteria for the protocol

          -  ECOG PS 0, 1 or 2

          -  For women of childbearing potential a negative serum pregnancy test is required within
             4 weeks of starting cycle 1 and then every 4 weeks during the first 4 cycles of
             induction therapy

          -  Women of child bearing potential must be willing to refrain from sexual intercourse or
             willing to employ a dual method of contraception, one of which is highly effective
             (IUD, birth control pills, tubal ligation or partner's vasectomy) and another
             additional method (condom, diaphragm, or cervical cap) during the entire course of the
             study (start of therapy until 30 days after stem cell transplant).

          -  Sexually active males should be willing to use a condom (even if they have had a prior
             vasectomy) while having intercourse with any women during the course of the study
             (start of therapy until 30 days after stem cell transplant).

          -  Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care, with the understanding that consent may be withdrawn
             by the subject at any time without prejudice to future medical care.

        Exclusion Criteria:

          -  Patients with smoldering myeloma or monoclonal gammopathy of unknown significance are
             not eligible

          -  Age > 70 years or < 18 years is not eligible

          -  Patient has > 1.5 × ULN Total Bilirubin

          -  Grade 2 or higher peripheral neuropathy due to ANY cause

          -  High index of suspicion of primary amyloid light chain (AL) amyloidosis.

          -  Patients with uncontrolled inter-current illness including uncontrolled hypertension,
             symptomatic congestive heart failure, unstable angina, uncontrolled cardiac
             arrhythmia, uncontrolled psychiatric illness or social situation that would limit
             compliance or a prior history of Steven Johnson syndrome

          -  Patients must not have a history of current or previous deep vein thrombosis or
             pulmonary embolism regardless of whether or not the patient is receiving
             anticoagulation therapy

          -  Female patients who are breastfeeding or pregnant.

          -  Patients known to be HIV positive

          -  Myocardial infarction within 6 months prior to enrollment or has New York Heart
             Association (NYHA) Class III or IV heart failure (see section 31.3), 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 hypersensitivity to VELCADE, boron or mannitol.

          -  Patient has received other investigational drugs within 14 days before enrollment

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.