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Adoptive Cellular Immunotherapy Following Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma

1 marzo 2019 aggiornato da: Kenneth Meehan, Dartmouth-Hitchcock Medical Center

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.

Panoramica dello studio

Stato

Completato

Tipo di studio

Interventistico

Iscrizione (Effettivo)

23

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

    • New Hampshire
      • Lebanon, New Hampshire, Stati Uniti, 03756
        • Dartmouth-Hitchcock Medical Center

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 75 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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)

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Altro: 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.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of Participants With Adverse Events in All Subjects
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Count of Participants With Increased CD3+CD8+, CD8+ and CD56+ Concentrations Between Day 15 Post-Transplant and Days 21 to 28 Post-transplant
Lasso di tempo: 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:

  • Dye Dilution Proliferation Assay (DDPA) 36 - Evaluation of CD8+ T Cell Precursors
  • ELISPOT-Quantifying cytokine producing T cells:
Day 15 post-transplant and between days 21 to 28 post-transplant
Time to Recovery of Absolute Neutrophil Count
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: Pre-transplant and following the third and fourth cellular infusions
  • Isolate CD3+CD8+ and CD8+CD56+ from patients' blood following transplant.
  • Identify NKG2D and DAP10 expression.
  • Determine the mechanism of tumor cell killing and the relationship to NKG2D or DAP 10 expression.

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)
Lasso di tempo: 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.

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 gennaio 2007

Completamento primario (Effettivo)

15 ottobre 2012

Completamento dello studio (Effettivo)

30 novembre 2012

Date di iscrizione allo studio

Primo inviato

21 febbraio 2007

Primo inviato che soddisfa i criteri di controllo qualità

22 febbraio 2007

Primo Inserito (Stima)

23 febbraio 2007

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

26 marzo 2019

Ultimo aggiornamento inviato che soddisfa i criteri QC

1 marzo 2019

Ultimo verificato

1 marzo 2019

Maggiori informazioni

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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