- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus 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.
Tutkimuksen yleiskatsaus
Tila
Interventio / Hoito
Opintotyyppi
Ilmoittautuminen (Todellinen)
Vaihe
- Vaihe 2
Yhteystiedot ja paikat
Opiskelupaikat
-
-
New Hampshire
-
Lebanon, New Hampshire, Yhdysvallat, 03756
- Dartmouth-Hitchcock Medical Center
-
-
Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
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)
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Ei käytössä
- Inventiomalli: Yksittäinen ryhmätehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
|
Muut: 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.
|
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Number of Participants With Adverse Events in All Subjects
Aikaikkuna: 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
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Count of Participants With Increased CD3+CD8+, CD8+ and CD56+ Concentrations Between Day 15 Post-Transplant and Days 21 to 28 Post-transplant
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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)
Aikaikkuna: 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.
|
Yhteistyökumppanit ja tutkijat
Sponsori
Yhteistyökumppanit
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus
Ensisijainen valmistuminen (Todellinen)
Opintojen valmistuminen (Todellinen)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Arvio)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
- Sydän-ja verisuonitaudit
- Verisuonisairaudet
- Immuunijärjestelmän sairaudet
- Neoplasmat histologisen tyypin mukaan
- Neoplasmat
- Lymfoproliferatiiviset häiriöt
- Immunoproliferatiiviset häiriöt
- Hematologiset sairaudet
- Hemorragiset häiriöt
- Hemostaattiset häiriöt
- Paraproteinemiat
- Veren proteiinien häiriöt
- Multippeli myelooma
- Neoplasmat, plasmasolut
Muut tutkimustunnusnumerot
- D0717
Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .