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A Pediatric Study of a Plerixafor Containing Regimen In Second Allogeneic Stem Cell Transplantation

31 december 2013 uppdaterad av: St. Jude Children's Research Hospital

A Phase I Pediatric Study of a Plerixafor Containing Regimen In Second Allogeneic Stem Cell Transplantation

Patients with refractory hematologic malignancies, including those who develop recurrent disease after allogeneic hematopoietic stem cell transplantation (HSCT) have a dismal prognosis. Historically, both regimen-related mortality and disease recurrence have been significant causes of treatment failure in this heavily pre-treated patient population. Novel therapeutic agents that target molecular signaling mechanisms and increase the sensitivity of leukemic cells to apoptosis may clearly play a role in this setting.

This study hypothesizes that interrupting the SDF-1/CXCR4 axis using the selective CXCR4 antagonist plerixafor may be useful as a leukemic stem cell mobilizing agent for patients who are refractory to standard dose chemotherapy and in relapse after an allogeneic transplant. This hypothesis is based on the dependence of leukemia cells on MSCs for survival signals as described above and on the preclinical data that suggest increased efficacy by antileukemia agents when leukemia cells are separated from MSCs.

In the present trial, the study proposes to add plerixafor to enhance the conditioning regimen cytotoxicity. At this time the goal is to determine the maximum tolerated dose (MTD) of plerixafor through the process of dose limiting toxicity (DLT) evaluation. Pharmacokinetic studies will be conducted. Additional studies will quantify and the content of leukemia cells and key regulatory and effector T cell populations in the bone marrow and blood before and after exposure to this medication.

If the observed outcomes of this trial are promising, it could serve as a platform on which to study further use of plerixafor as a complimentary agent with conditioning as well as other chemotherapeutic regimens for patients with relapsed or refractory hematologic malignancies.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

This study will determine the following objectives:

  1. To determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of plerixafor in combination with fludarabine, thiotepa, and melphalan as a conditioning regimen for children and young adults undergoing a second allogeneic stem cell transplant (SCT) procedure.

  2. The study determines the secondary objectives:

    • To describe the pharmacokinetic properties of plerixafor in this study population
    • To estimate the cumulative incidence of relapse and overall survival in study participants at one year after this second transplant procedure

  3. Other exploratory objectives include:

    • To study the correlation between the pharmacokinetic properties of plerixafor and key regulatory and effector T cell populations in blood before and after exposure to plerixafor.
    • To evaluate the content of leukemia cells in bone marrow and in blood before and after exposure to plerixafor
    • To evaluate key regulatory and effector T cell populations in bone marrow and in blood before and after exposure to plerixafor

Studietyp

Interventionell

Inskrivning (Faktisk)

12

Fas

  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Förenta staterna
    • Tennessee
      • Memphis, Tennessee, Förenta staterna, 38105
        • St. Jude Children's Research Hospital

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

Inte äldre än 21 år (Barn, Vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  • Age less than or equal to 21 years old.
  • One of the following hematologic malignancies that has relapsed after prior allogeneic hematopoietic stem cell transplantation:
  • Acute lymphoblastic leukemia (ALL)
  • Acute myeloid leukemia (AML)
  • Myelodysplastic syndrome (MDS)
  • Chronic myeloid leukemia (CML)
  • Juvenile myelomonocytic leukemia (JMML)
  • Non-Hodgkin's lymphoma (NHL) with evidence of bone marrow disease
  • Has a suitable human leukocyte antigen (HLA) matched family member or unrelated donor available for stem cell donation. A "matched" donor is defined as matching at 5/6 or 6/6 HLA loci.
  • Does not have active central nervous system (CNS) malignancy (history of CNS disease allowed).
  • No prior neuromuscular dysfunction or all prior grade I-IV neuromuscular dysfunctions have subsided > 4 weeks prior to enrollment.
  • Cardiac shortening fraction greater than or equal to 25%.
  • Creatinine clearance greater than or equal to 50 ml/min/1.73 m2
  • Forced vital capacity (FVC) greater than or equal to 40% of predicted value or pulse oximetry greater than or equal to 92% on room air.
  • Karnofsky or Lansky (age-dependent) performance score of greater than or equal to 50 .
  • Off all treatment for acute or chronic graft-versus-host disease (GVHD) for at least 7 days prior to the initiation of conditioning.
  • Bilirubin less than or equal to 3 times the upper limit of normal for age.
  • Alanine aminotransferase (ALT) less than or equal to 3.0 times the upper limit of normal for age.
  • White blood cell count of less than 50,000/mm3
  • Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment.
  • Not lactating.
  • All patients of childbearing potential must agree to use an effective birth control method

Exclusion Criteria:

  • Pregnant and lactating females are excluded from participation as the short and long-term effects of the preparative agents and infusion on a fetus and a nursing child through breast milk are not entirely known at this time.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Övrig: Second Allogeneic Transplant Procedure Recipient

Participants with Acute Lymphoblastic Leukemia (ALL); Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS); Chronic Myeloid Leukemia (CML); Juvenile Myelomonocytic Leukemia (JMML); Non-Hodgkin lymphoma (NHL) with evidence of bone marrow disease, receiving a second allogeneic transplant procedure.

Intervention: Plerixafor
Läkemedel: Plerixafor
Plerixafor in combination with fludarabine, thiotepa and melphalan as a conditioning regimen for patients undergoing a second allogeneic transplant procedure (bone marrow or peripheral blood). A traditional 3+3 phase I design will be employed during this study, where dose escalations are planned in groups of 3 participants. No intra-participant escalation will be allowed and dose escalation will not be considered until toxicity information is available from at least 3 evaluable participants at the current dose level.Plerixafor will be given intravenously (IV) rather than subcutaneously (SQ) to minimize discomfort associated with repeated daily injections (up to 3) to the pediatric population of this study.
Andra namn:
  • AMD3100
  • Mozobil®

Vad mäter studien?

Primära resultatmått

Resultatmått
Tidsram
To determine the dose-limiting toxicity and maximum tolerated dose of plerixafor in combination with fludarabine, thiotepa and melphalan as a conditioning regimen for patients undergoing a second allogeneic transplant procedure.
Tidsram: 7 days post transplant
7 days post transplant

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

St. Jude Children's Research Hospital

Samarbetspartners

Genzyme, a Sanofi Company

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Användbara länkar

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 maj 2010

Primärt slutförande (Faktisk)

1 oktober 2013

Avslutad studie (Faktisk)

1 oktober 2013

Studieregistreringsdatum

Först inskickad

11 februari 2010

Först inskickad som uppfyllde QC-kriterierna

11 februari 2010

Första postat (Uppskatta)

12 februari 2010

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

1 januari 2014

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

31 december 2013

Senast verifierad

1 december 2013

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • MOZBMT

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