A Pediatric Study of a Plerixafor Containing Regimen In Second Allogeneic Stem Cell Transplantation
| Status: | Completed |
|---|---|
| Conditions: | Cancer, Blood Cancer, Lymphoma, Hematology |
| Therapuetic Areas: | Hematology, Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 11/18/2012 |
| Start Date: | May 2010 |
| End Date: | October 2013 |
| Contact: | Ashok Srinivasan, MD |
| Email: | info@stjude.org |
| Phone: | 1-866-278-5833 |
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.
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 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
- To estimate the cumulative incidence of relapse and overall survival in study
participants at one year after this second transplant procedure
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.
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