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Stem Cell Transplantation as Immunotherapy for Hematologic Malignancies

28. Januar 2009 aktualisiert von: St. Jude Children's Research Hospital

Haploidentical Hematopoietic Stem Cell Transplantation Utilizing Partial T-Cell Depletion as Immunotherapy for Hematologic Malignancies

Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor.

Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including GVHD and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection.

For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality.

Two groups of patients were enrolled on this study. One group included those with high-risk hematologic malignancies and the second group included participants with refractory hematologic malignancies or undergoing a second transplant. The primary aim of the study was to estimate the relapse rate in the one group of research participants with refractory hematologic malignancies or those undergoing second allogeneic transplant. Both groups will be followed and analyzed separately in regards to the secondary objectives.

This study was closed to accrual on April 2006 as it met the specific safety stopping rules regarding occurrence of severe graft vs. host disease. Although this study is no longer open to accrual, the treated participants continue to be followed as directed by the protocol.

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

Secondary outcome evaluations for this clinical study included the following:

  • To estimate one-year overall survival for research participants with high risk malignancies who receive a haploidentical HSCT
  • To compare overall survival and cumulative incidence of relapse for the two groups of patients with their corresponding historical controls
  • To estimate disease-free survival and event-free survival in participants with hematologic malignancies who receive a haploidentical HSCT
  • To estimate the incidence of overall grade 3-4 acute GvHD in research participants with hematologic malignancies who receive a haploidentical HSCT
  • To estimate the incidence of chronic GvHD and graft failure in research participants with hematologic malignancies who receive a haploidentical HSCT
  • To estimate the incidence of non-hematologic regimen-related toxicity and regimen-related mortality in the first 100 days post-transplant in research participants with hematologic malignancies who receive a haploidentical HSCT
  • To estimate the number of research participants who develop evidence of EBV reactivation or post-transplant lymphoproliferative disease (PTLPD)
  • To describe disease-free survival, GvHD and engraftment in research participants receiving grafts from Killer immunoglobulin-like receptor (KIR) mismatched and KIR matched haploidentical donors

Studientyp

Interventionell

Einschreibung (Tatsächlich)

17

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

  • Vereinigte Staaten
    • Tennessee
      • Memphis, Tennessee, Vereinigte Staaten, 38105
        • St. Jude Children's Research Hospital

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

2 Jahre bis 21 Jahre (Kind, Erwachsene)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

Inclusion Criteria:

Eligible participants were assigned to one of two different strata dependent on diagnosis, disease status and/or past transplant experience. Both strata received the same intervention but will be followed and analyzed separately.

  • Group A must have one of the following diagnosis

    • Acute lymphoid leukemia (ALL) in second or subsequent remission or high risk in first remission
    • Acute myeloid leukemia (AML) in remission or with ≤ 25% blasts in bone marrow
    • Chronic myeloid leukemia (CML)
    • Juvenile myelomonocytic leukemia (JMML)
    • Myelodysplastic syndrome (MDS)
    • Paroxysmal nocturnal hemoglobinuria (PNH)
    • Hodgkin's (HD) or non-Hodgkin's lymphoma (NHL) in second or subsequent remission after autologous HSCT, or unable to have hematopoietic stem cells collected for autologous HSCT

  • Group B must have one of the following refractory diagnosis (chemoresistant relapse or primary induction failure)

    • Acute lymphoid leukemia (ALL)
    • Acute myeloid leukemia (AML) ≥ 25% blast in bone marrow
    • Secondary AML / MDS
    • Chronic myeloid leukemia (CML) in accelerated phase or blast crisis
    • Juvenile myelomonocytic leukemia (JMML)
    • Myelodysplastic syndrome (MDS)
    • Hodgkin's (HD) or non-Hodgkin's lymphoma (NHL) with residual disease followed by autologous HSCT or who have chemo-resistant disease
    • Or patients who have undergone prior allogeneic HSCT or who have a co-morbid condition that in the medical opinion of the Transplant Faculty makes standard myeloablation prohibited
  • At least 2 and less than or equal to 21 years of age
  • Lacks suitable HLA-identical sibling or matched available unrelated donor and has a mismatched family member donor that is available, HIV negative and at least 18 years old
  • Cardiac shortening fraction ≥ 25%
  • Creatinine clearance ≥ 40 cc/min/1.73m^2
  • FVC ≥ 40% of predicted or pulse oximetry ≥ 92% on room air
  • Direct bilirubin ≤ 3 mg/dL or SGPT ≤ 500 U/L
  • Karnofsky or Lansky (age dependent) performance score of ≥ 50

Exclusion Criteria:

  • Known allergy to murine products
  • Lactating (female patient)
  • Pregnancy (female patient)
  • Active central nervous system (CNS) leukemia

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Nicht randomisiert
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Sonstiges: 1
Arzneimittel: Systematic chemotherapy and antibodies

Systemic chemotherapy and antibodies as follows:

Transplant recipients received a reduced intensity conditioning regimen consisting of OKT-3, fludarabine, thiotepa, and melphalan followed by an infusion of a T-cell depleted haploidentical hematopoietic stem cell graft. The antibody Rituximab was administered within 24 hours of the infusion in an effort to prevent PTLPD. In addition to T -cell depletion of the donor product, Mycophenylate mofetil was provided over several months as prophylaxis for GVHD

Verfahren: Allogeneic stem cell transplantation
An infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device
Gerät: Miltenyi CliniMACS
Miltenyi Biotec CliniMACS stem cell selection device
Andere Namen:
  • Allogene Stammzelltransplantation
  • Hämatopoetische Stammzelltransplantation
  • Haploidentical donor stem cell transplant
  • Mismatched family member transplant
  • Reduced intensity conditioning regimen

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Zeitfenster
To measure the rate of disease relapse by six months posttransplant in children and young adults with refractory hematologic malignancies who receive a haploidentical stem cell graft processed using the investigational CliniMACS cell sorting device.
Zeitfenster: September 2006
September 2006

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

St. Jude Children's Research Hospital

Ermittler

  • Hauptermittler: Gregory Hale, M.D., St. Jude Children's Research Hospital

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Nützliche Links

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. August 2005

Primärer Abschluss (Tatsächlich)

1. Juli 2006

Studienabschluss (Tatsächlich)

1. Januar 2009

Studienanmeldedaten

Zuerst eingereicht

1. September 2005

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

1. September 2005

Zuerst gepostet (Schätzen)

2. September 2005

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Schätzen)

29. Januar 2009

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

28. Januar 2009

Zuletzt verifiziert

1. Januar 2009

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • HAPREF

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