- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00439465
Adoptive Cellular Immunotherapy Following Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
New Hampshire
-
Lebanon, New Hampshire, United States, 03756
- Dartmouth-Hitchcock Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Ex-vivo expanded effector cells
Infusing IL-2 and GM-CSF post-Hematopoietic Stem Cell Transplant (HSCT)
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Adverse Events in All Subjects
Time Frame: From initiation of treatment on protocol until Day 100
|
To establish the safety (toxicity) of myeloma patients treated with high dose melphalan, autologous peripheral blood stem cell transplantation (APBSCT) & adoptive transfer of cytotoxic effector cells with Interleukin-2 (IL-2) and Recombinant Human Granulocyte Colony Stimulating Factor (GM-CSF).
|
From initiation of treatment on protocol until Day 100
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Count of Participants With Increased CD3+CD8+, CD8+ and CD56+ Concentrations Between Day 15 Post-Transplant and Days 21 to 28 Post-transplant
Time Frame: Day 15 post-transplant and between days 21 to 28 post-transplant
|
To demonstrate that the effector cell infusions result in a clinical effect, phenotypic analyses of blood samples using flow cytometry will be performed prior to, and after each infusion, focusing on the CD8 + populations (CD3+CD8+, CD8+CD56+). As a complement to flow cytometry, the following assays will be used to identify cell subset precursor frequencies, subset proliferation, and cytokine production:
|
Day 15 post-transplant and between days 21 to 28 post-transplant
|
Time to Recovery of Absolute Neutrophil Count
Time Frame: From initiation of treatment on protocol until Day 100
|
To establish the time to engraftment of myeloma patients treated with high dose melphalan, APBSCT& adoptive transfer of cytotoxic effector cells with IL-2 and GM-CSF.
|
From initiation of treatment on protocol until Day 100
|
Time to Recovery of Platelet Count
Time Frame: From initiation of treatment on protocol until Day 100
|
To establish the time to engraftment of myeloma patients treated with high dose melphalan, APBSCT& adoptive transfer of cytotoxic effector cells with IL-2 and GM-CSF.
|
From initiation of treatment on protocol until Day 100
|
Assessment of Disease Response to Treatment
Time Frame: From initiation of treatment on protocol until Day 100
|
To establish the disease response of myeloma patients treated with high dose melphalan, APBSCT& adoptive transfer of cytotoxic effector cells with IL-2 and GM-CSF.
|
From initiation of treatment on protocol until Day 100
|
Number of Participants With Increased Expression of DAP10 and NKG2D on the CD8 Cell Population
Time Frame: Pre-transplant and following the third and fourth cellular infusions
|
After isolating CD8+ cells from patient's blood samples using the AutoMACS, we will evaluate the expression of NKG2D and DAP10 on all CD8+ cells (CD3+CD8+ and CD8+CD56+cells) pre-transplant (Baseline) and following the third and fourth cellular infusions using phenotypic analysis. We postulate the increased expression of both DAP10 and NKG2D on the CD8 population immediately following APSCT and effector cell infusions when compared to baseline. |
Pre-transplant and following the third and fourth cellular infusions
|
Determine the Methods of Tumor Cell Killing of the in Vivo CD8+ Cells: Cytotoxicity Assays, Blocking Experiments, Analysis of T-cell Receptor (TCR)
Time Frame: Pre-transplant and following the third and fourth cellular infusions.
|
We will isolate the CD8+ populations (CD3+CD8+, CD8+CD56+) using the Auto MACS (Miltenyi) and then identify the mechanisms of tumor cell killing by the CD8+ cells obtained pre-transplant (Baseline) and following the third and fourth cellular infusions.
We will examine mechanisms of tumor cell killing through NKG2D receptor, major histocompatibility complex (MHC) Class I molecules or through the T cell receptor.
We postulate the CD8+ cells obtained from patient's blood will kill tumor cells both via MHC Class I and through the NKG2D receptor.
|
Pre-transplant and following the third and fourth cellular infusions.
|
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
Other Study ID Numbers
- D0717
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Myeloma
-
Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University; Niagara Health SystemActive, not recruitingMultiple Myeloma in Relapse | Multiple Myeloma With Failed Remission | Multiple Myeloma Stage I | Multiple Myeloma Progression | Multiple Myeloma Stage II | Multiple Myeloma Stage IIICanada
-
Tel-Aviv Sourasky Medical CenterCompletedPlasma Cell Myeloma | Myeloma-Multiple | Myeloma Multiple | Myeloma, Plasma-CellIsrael
-
Albert Einstein College of MedicineNational Cancer Institute (NCI)TerminatedRefractory Plasma Cell Myeloma | DS Stage II Plasma Cell Myeloma | DS Stage III Plasma Cell Myeloma | DS (Durie/Salmon) Stage I Plasma Cell MyelomaUnited States
-
Albert Einstein College of MedicineNational Cancer Institute (NCI)CompletedRefractory Plasma Cell Myeloma | DS Stage I Plasma Cell Myeloma | DS Stage II Plasma Cell Myeloma | DS Stage III Plasma Cell MyelomaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedRefractory Plasma Cell Myeloma | DS Stage I Plasma Cell Myeloma | DS Stage II Plasma Cell Myeloma | DS Stage III Plasma Cell MyelomaUnited States
-
National Cancer Institute (NCI)Active, not recruitingSmoldering Multiple Myeloma | Refractory Multiple Myeloma | DS Stage I Multiple Myeloma | DS Stage II Multiple Myeloma | DS Stage III Multiple MyelomaUnited States
-
Mayo ClinicNational Cancer Institute (NCI)CompletedRefractory Plasma Cell Myeloma | DS Stage I Plasma Cell Myeloma | DS Stage II Plasma Cell Myeloma | DS Stage III Plasma Cell MyelomaUnited States
-
National Cancer Institute (NCI)CompletedRefractory Plasma Cell Myeloma | DS Stage I Plasma Cell Myeloma | DS Stage II Plasma Cell Myeloma | DS Stage III Plasma Cell MyelomaUnited States
-
US Oncology ResearchKaryopharm Therapeutics IncRecruitingMultiple Myeloma | Plasma Cell Myeloma | Myeloma-Multiple | Myeloma Multiple | Kahler Disease | Myeloma, Plasma Cell | MyelomatosisUnited States
-
University of WashingtonNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
Clinical Trials on Ex-vivo expanded effector cells
-
Institute of Hematology & Blood Diseases HospitalCancer Institute and Hospital, Chinese Academy of Medical Sciences; Beijing...RecruitingNon-Hodgkin's Lymphoma (NHL) | Peripheral T Cell Lymphoma (PTCL)China
-
Beijing 302 HospitalCancer Institute and Hospital, Chinese Academy of Medical Sciences; Beijing...UnknownHepatocellular CarcinomaChina
-
Clinica Universidad de Navarra, Universidad de...Spanish National Health SystemUnknownFollicular Lymphoma | Follicular Non-Hodgkin´s Lymphoma | Autologous Effector LymphocytesSpain
-
King Edward Medical UniversityUnknownLipodystrophy | Craniofacial Microsomia | Mixed Connective Tissue Disease | Romberg's Disease
-
National Institute of Allergy and Infectious Diseases...Autoimmunity Centers of ExcellenceTerminatedLupus Erythematosus, Systemic | Lupus Erythematosus, Cutaneous | Lupus Erythematosus, DiscoidUnited States
-
Nationwide Children's HospitalCompletedOsteogenesis Imperfecta Type III | Osteogenesis Imperfecta Type IIUnited States
-
Singapore General HospitalWhitehead Institute for Biomedical Research; Blood Services Group, Health Sciences...TerminatedLymphoma | Acute Leukemia | Myelodysplastic Syndrome | Myeloma | Chronic LeukemiaSingapore
-
Jeffrey BluestoneNational Institute of Allergy and Infectious Diseases (NIAID); Immune Tolerance...TerminatedAcute Respiratory Distress Syndrome Due to Disease Caused by 2019-nCoVUnited States
-
Wuhan Union Hospital, ChinaJinan University, ChinaUnknownAcute Myeloid LeukemiaChina
-
University of California, San FranciscoNational Institute of Allergy and Infectious Diseases (NIAID); Juvenile Diabetes...CompletedType 1 Diabetes MellitusUnited States