Th1/Tc1 Immunotherapy Following Stem Cell Transplantation in Multiple Myeloma

• INCLUSION CRITERIA:

MULTIPLE MYELOMA CRITERIA:

Criteria for newly or recently diagnosed subjects

-Presence of clonal plasma cells in the bone marrow greater or equal to 10% or a documented clonal plasmacytoma

AND

-Presence of an M-component; an M-component (IgG or IgA) in serum greater or equal to 1g/dl or in urine greater or equal to 200 mg/24 h.

ALTERNATIVELY, in absence of an M-component greater or equal to 1g/dl:

• an abnormal serum free light chain (FLC) ratio on the serum FLC assay or if the FLC ratio is normal,
• baseline bone marrow must have 10% or greater clonal plasma cells.

AND, IN ADDITION:

• Presence, of one or more of the following attributable to the disease (in the presence or absence of an M component):

  • Calcium elevation greater than 11.5 mg/dl (2.65 mmol/l)
  • Renal insufficiency: serum creatinine greater than 2 mg/dl (177 mmol/l)
  • Hemoglobin less than 10g/dl (12.5 mmol/l) or 2 g/dl (1.25 mmol/l) below lower normal
  • Bone disease (lytic lesions or osteopenia)
  • Other evidence of disease activity: repeated infections, secondary amyloidosis, hyperviscosity, hypogammablobulinemia

• Must have high risk disease defined as the presence of any of the following:

  • Stage II and III of the International Staging System defined as follows:

    • stage I: - serum (Beta)2-microglobulin less than 3.5 mg/l plus

      -----serum albumin greater or equal to 3.5 g/dl

    • stage II: neither stage I nor III

    • stage III: serum (Beta)2-microglobulin greater or equal to 5.5 mg/L

      • del 13 or aneuploidy (by metaphase analysis33)
      • del 17p13 by FISH or mutated p53
      • (4;14) by FISH31
      • (14;16) or t(14;20) by FISH
      • plasmablastic morphology at diagnosis(35)
      • circulating myeloma cells by FACS (CD38+/CD45low) post induction therapy(36)
      • High-risk disease as defined in a 70-gene ( MyPRS (TM)) or the 17-gene condensed microarrays

OTHER ELIGIBILITY CRITERIA:

• Age greater than or equal to 18 years and less than or equal to 75 years. In subjects between 65 and 75 years of age, physiologic age and co-morbidity will be thoroughly evaluated before enrolling.
• Specifically, any history of cardio-vascular pathology or symptoms, not clearly fitting the exclusion criteria will prompt an evaluation by a Clinical Center Cardiologist and eligibility wil be considered on a case-by-case basis
• Must have received no more than 6 cycles of induction therapy for Multiple Myeloma.
• The planned High-Dose chemotherapy must consist of melphalan only and may be followed by a post-ASCT consolidation.
• Karnofsky performance status of 70% or greater (ECOG 0 or 1). Lower KPS down to 50% or ECOG of 2 may be acceptable if the restriction of activity is solely due to intractable pain from myeloma lesions.
• Ejection fraction (EF) by MUGA or 2-D echocardiogram within institution normal limits. In case of low EF, the subject may remain eligible after a stress echocardiogram is performed if the EF is more than 35% and if the increase in EF with stress is estimated at 10% or more.
• Serum creatinine less than or equal to 2.5 mg/dl,
• AST and ALT less than or equal to 3 times the upper limit of normal,
• Bilirubin less than or equal to1.5 (except if due to Gilbert's disease).
• Corrected DLCO greater than or equal to 50% on Pulmonary Function Tests
• No history of abnormal bleeding tendency or predisposition to repeated infections.
• Patients must be able to give informed consent

DECISION TO ENROLL ON COHORT 5 B

The decision to enroll on cohort 5B or on cohort 6 will be made as follows:

• A subject will be enrolled on the cohort that has the smallest number of accrued subjects of these two cohorts.
• In case of a tie, the subject will be enrolled on the cohort that did not enroll the previous subject.

EXCLUSION CRITERIA:

• Prior allogeneic stem cell transplantation
• Hypertension not adequately controlled by 3 or less medications.
• History of cerebro-vascular accident within 6 months of enrollment..
• History of documented pulmonary embolus within 6 months of enrollment.
• Clinically significant cardiac pathology: myocardial infarction within 6 months prior to enrollment, Class III or IV heart failure according to NYHY, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Patients with a history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis.
• HIV seropositive
• Patients known or found to be pregnant.
• Patients of childbearing age who are unwilling to practice contraception.
• Patients may be excluded at the discretion of the PI if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk.