Adoptive Cellular Immunotherapy Following Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma
Condition: Myeloma; Transplant-eligible Patients
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Ex-vivo expanded effector cells
Intervention description: This trial will test if the combination of infusing ex vivo expanded cytotoxic effector cells with IL-2 and GM-CSF post-transplant will accelerate immune reconstitution, resulting in an effector cell-versus-myeloma effect and, possibly, improved clinical outcomes.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether the administration of highly effective
      "killer" cells (cytotoxic T cells), along with Interleukin-2 (IL-2) and Recombinant Human
      Granulocyte Colony Stimulating Factor (GM-CSF) immediately following Autologous Peripheral
      Blood Stem Cell Transplantation (APBSCT) will enhance anti-tumor immune reconstitution and
      improve outcome of Multiple Myeloma patients.

      The overall hypothesis of this proposal is that immediately following APBSCT the immune
      reconstitution is optimal to administer "killer" cells, combined with the administration of
      IL-2 and GM-CSF.
    

Eligibility criteria:

        Inclusion Criteria:

        Multiple Myeloma:

          -  Patients must meet criteria for diagnosis of Multiple Myeloma.

          -  Patient must meet either criterion listed below:

               -  Stage I, II, or III newly diagnosed multiple myeloma

               -  Progressive or relapsed disease in partial response (PR) or complete response
                  (CR)

               -  Primary refractory disease.

               -  Relapsed refractory disease.

               -  Patients may have received a prior autologous transplant.

          -  The patients must have recovered from all serious and life threatening effects of
             previous treatment at the time of study entry (unless this abnormality is believed to
             be due to the underlying myeloma).

          -  The patient must have adequate bone marrow function, i.e. a total white blood cell
             count (WBC) of > 2,000/ul, a Hemoglobin (Hgb) of > 7 gm/dl, and a platelet count of >
             50,000/ul, unless this abnormality is believed to be due to the underlying myeloma.

          -  The patient must have adequate liver function, i.e. bilirubin <2.0 mg/dl, aspartate
             aminotransferase (SGOT), alanine aminotransferase (SGPT) not greater than 2 times the
             upper normal limit (unless this abnormality is believed to be due to the underlying
             myeloma).

          -  The patient must have adequate renal function, i.e. serum creatinine < 3.0 mg/dl,
             and/or creatinine clearance >50 ml/min. This eligibility criterion is excluded if
             renal insufficiency is believed to be secondary to myeloma.

          -  Age >18 years and < 75 years old

          -  The patient must have a Karnofsky status > 80%

          -  Patients must have a life expectancy of at least 12 weeks

          -  Left ventricular ejection fraction of > 45% by radionuclide scan or echocardiography

          -  Pulmonary function tests: forced vital capacity, Diffusing capacity of the lungs for
             carbon monoxide (DLCO) and expiratory volume in one second (FEV1) must be > 50% of
             predicted

          -  No significant co-morbid medical or psychiatric illness which would significantly
             compromise the patient's clinical care and chances of survival.

          -  Informed written consent must be obtained. Patients must be able to give informed
             consent as a prerequisite to this procedure. The Informed Consent form will become
             part of his/her permanent record and a copy will be given to the patient

        Exclusion Criteria:

          -  Medical, social, or psychological factors which would prevent the patient from
             receiving or cooperating with the full course of therapy.

          -  Evidence on physical exam, lumbar puncture, computed tomography (CT), or magnetic
             resonance imaging (MRI) scan of central nervous system (CNS) involvement with
             malignancy

          -  Any clinically significant cardiac disease (angina, myocardial infarction, congestive
             heart failure, ventricular arrhythmias requiring therapy) or clinically significant
             obstructive/restrictive pulmonary disease

          -  Serology positive for human immunodeficiency virus (HIV) or human T-lymphotropic virus
             (HTLVI)

          -  Active hepatitis B or C

          -  History of seizures

          -  Concurrent or expected need for therapy with corticosteroids

          -  Active connective tissue disease

          -  Current "clinically significant" pleural effusion, pericardial effusion, or ascites

          -  Positive pregnancy test or presence of lactation

          -  Collection of fewer than 1 x 106 cluster of differentiation 34 positive (CD34+)
             cells/kg (peripheral blood stem cells). If the apheresis collection is inadequate
             based on this criteria, the patient will be removed from protocol and a marrow harvest
             may be performed

          -  A history of a second malignancy (other then squamous cell/ basal cell carcinoma of
             the skin or cervical dysplasia) must be reviewed by the Principal Investigator, before
             inclusion or exclusion in the study. Based upon the PI's review, this patient may be
             eligible (i.e., distant past history of a malignancy)