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

2014-08-27 03:15:55 | BioPortfolio


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 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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Acute Lymphoblastic Leukemia




St. Jude Children's Research Hospital
United States




St. Jude Children's Research Hospital

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:15:55-0400

Clinical Trials [2223 Associated Clinical Trials listed on BioPortfolio]

Study of Plerixafor Combined With Cytarabine and Daunorubicin in Patients With De Novo Acute Myeloid Leukemia

The purpose of this research study is to determine if Plerixafor can release cells into the blood and make them more sensitive to killing by Cytarabine and Daunorubicin, an anti-cancer dru...

Chemosensitization With Plerixafor Plus G-CSF in Acute Myeloid Leukemia

This study is designed to test the combination of Plerixafor with G-CSF for chemosensitization in patients with relapsed or refractory AML.

Diagnostic Study of Patients With Acute Lymphoblastic Leukemia or Acute Promyelocytic Leukemia

RATIONALE: Determination of genetic markers for acute lymphoblastic leukemia and acute promyelocytic leukemia may help identify patients with this disease and help predict the outcome of t...

The Expression of CD 95, CD20, CD34 and CD44 in Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia , also known as acute lymphocytic leukemia, characterized by the overproduction and accumulation of cancerous, immature white blood cells, known as lymphoblast...

Phase II Study of Clofarabine in Pediatric Acute Lymphoblastic Leukemia (ALL)

Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 1 to 21 years old with relapsed acute lymphoblastic leukemia (ALL) who...

PubMed Articles [6481 Associated PubMed Articles listed on BioPortfolio]

Hypophyseal involvement of acute lymphoblastic leukemia.

We present an unusual case of hypophyseal involvement in a boy with acute lymphoblastic leukemia via magnetic resonance (MR) imaging findings. In our case, the acute lymphoblastic leukemia of the pitu...

Combination therapy of omega-3 fatty acids and acipimox for children with hypertriglyceridemia and acute lymphoblastic leukemia.

Lipemic alterations are commonly seen in pediatric patients with acute lymphoblastic leukemia (ALL) treated with corticosteroids and L-asparaginase.

Body Mass Index (BMI) and Infectious/Febrile Episodes in Children with Intermediate Risk Acute Lymphoblastic Leukemia (IR ALL).

The incidence of treatment related mortality in children with acute lymphoblastic leukemia (ALL) is reported to be between 2% and 4% with infections being the leading cause.

Novel Therapies in Acute Lymphoblastic Leukemia.

Treatment options for patients with acute lymphoblastic leukemia (ALL) beyond standard chemotherapy have grown significantly in recent years. In this review, we highlight new targeted therapies in ALL...

TLE1 as an indicator of adverse prognosis in pediatric acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children, and despite the high rate of cure (over 80%) it still has a big impact on morbidity and mortality. The Transducin-like...

Medical and Biotech [MESH] Definitions

A tyrosine kinase inhibitor and ANTINEOPLASTIC AGENT that inhibits the BCR-ABL kinase created by chromosome rearrangements in CHRONIC MYELOID LEUKEMIA and ACUTE LYMPHOBLASTIC LEUKEMIA, as well as PDG-derived tyrosine kinases that are overexpressed in gastrointestinal stromal tumors.

A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)

Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.

A leukemia/lymphoma found predominately in children and adolescents and characterized by a high number of lymphoblasts and solid tumor lesions. Frequent sites involve LYMPH NODES, skin, and bones. It most commonly presents as leukemia.

A rare acute myeloid leukemia characterized by abnormal EOSINOPHILS in the bone marrow.

More From BioPortfolio on "A Pediatric Study of a Plerixafor Containing Regimen In Second Allogeneic Stem Cell Transplantation"

Quick Search


Relevant Topic

Organ transplantation is the moving of an organ from one body to another or from a donor site to another location on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative ...

Searches Linking to this Trial