Clinical trial NCT00439465: Adoptive Cellular Immunotherapy Following Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma
Official title: Adoptive Cellular Immunotherapy Following Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myeloma
Transplant-eligible Patients
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: The Leukemia and Lymphoma Society
First posted: 2007-02-23
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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)

Primary outcomes:
measure: Number of Participants With Adverse Events in All Subjects
timeFrame: From initiation of treatment on protocol until Day 100
Secondary outcomes:
measure: Count of Participants With Increased CD3+CD8+, CD8+ and CD56+ Concentrations Between Day 15 Post-Transplant and Days 21 to 28 Post-transplant
timeFrame: Day 15 post-transplant and between days 21 to 28 post-transplant
measure: Time to Recovery of Absolute Neutrophil Count
timeFrame: From initiation of treatment on protocol until Day 100
measure: Time to Recovery of Platelet Count
timeFrame: From initiation of treatment on protocol until Day 100
measure: Assessment of Disease Response to Treatment
timeFrame: From initiation of treatment on protocol until Day 100
measure: Number of Participants With Increased Expression of DAP10 and NKG2D on the CD8 Cell Population
timeFrame: Pre-transplant and following the third and fourth cellular infusions
measure: Determine the Methods of Tumor Cell Killing of the in Vivo CD8+ Cells: Cytotoxicity Assays, Blocking Experiments, Analysis of T-cell Receptor (TCR)
timeFrame: Pre-transplant and following the third and fourth cellular infusions.
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Kenneth Meehan, MD
role: PRINCIPAL_INVESTIGATOR
References: