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

December 31, 2013 updated by: 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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: 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
Drug: 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.
Other Names:
  • AMD3100
  • Mozobil®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
Time Frame: 7 days post transplant
7 days post transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Jude Children's Research Hospital

Collaborators

Genzyme, a Sanofi Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2010

Primary Completion (Actual)

October 1, 2013

Study Completion (Actual)

October 1, 2013

Study Registration Dates

First Submitted

February 11, 2010

First Submitted That Met QC Criteria

February 11, 2010

First Posted (Estimate)

February 12, 2010

Study Record Updates

Last Update Posted (Estimate)

January 1, 2014

Last Update Submitted That Met QC Criteria

December 31, 2013

Last Verified

December 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MOZBMT

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.

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