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

NCT01068301 | Completed Phase 1

• 1 other identifier: MOZBMT
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma

Keywords

Allogeneic Stem Cell transplantation; Plerixafor; Acute Lymphoblastic leukemia; Acute Myeloid leukemia; Chronic Myeloid leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma; Other Leukemia

Outcome Measures

Primary Outcomes (1)

• 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.

  7 days post transplant

Study Arms (1)

Second Allogeneic Transplant Procedure Recipient

OTHER

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

Interventions

Plerixafor DRUG

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.

Also known as: AMD3100, Mozobil®

Second Allogeneic Transplant Procedure Recipient

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 .

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin

Interventions

plerixafor

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma

Study Officials

• Ashok Srinivasan, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2010
• First Posted: February 12, 2010
• Study Start: May 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: January 1, 2014

Record last verified: 2013-12

Locations

US (1)