Trial record 2 of 40 for:    phase I study of mozobil

POETIC Plerixafor as a Chemosensitizing Agent for Relapsed Acute Leukemia and MDS in Pediatric Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01319864
Recruitment Status : Active, not recruiting
First Posted : March 22, 2011
Last Update Posted : October 19, 2016
Children's Healthcare of Atlanta
Pediatric Oncology Experimental Therapeutics Investigation Consortium
Information provided by (Responsible Party):
Todd Cooper, Seattle Children's Hospital

Brief Summary:
In this Phase I study, we will test the safety of the drug plerixafor (MOBOZIL) at different dose levels, used together with other anti-cancer drugs—cytarabine and etoposide. We want to find out what effects, good and /or bad, this combination of drugs has on leukemia. Plerixafor is a drug that blocks a receptor on the leukemia cell, which prevents it from staying in the bone marrow where it can be resistant to chemotherapy. Plerixafor is FDA approved for mobilizing stem cells from the bone marrow in preparation for an autologous stem cell transplant. Cytarabine and etoposide have been used as part of standard chemotherapy for ALL and AML. However, the use of plerixafor with cytarabine and etoposide in pediatric patients with relapsed or refractory ALL, AML and MDS is considered experimental.

Condition or disease Intervention/treatment Phase
Relapsed/Refractory AML Relapsed/Refractory ALL Secondary AML/MDS Acute Leukemia of Ambiguous Lineage AML ALL Drug: Plerixafor Dose Escalation Phase 1

Detailed Description:

Approximately 500 children are diagnosed with AML every year, of whom around 60% are cured with current regimens based on anthracyclines and high dose cytarabine with or without stem cell transplant (SCT). Among the remaining 40% who are refractory or who relapse, outcome is dismal. Additionally, 20-30% of patients with childhood ALL relapse or become refractory to frontline therapies. The prognosis is poor in this patient population, particularly in patients with second or subsequent relapse and those who relapse following SCT. These patients present myriad challenges, as they usually have received a high cumulative anthracycline dose, and in the case of SCT, may have had significant organ toxicities and/or total body irradiation (TBI). Therefore, new therapeutic strategies need to be identified to enhance possible improved outcomes.

Recently, scientists have described a resistant, quiescent population of leukemia cells that have limitless self-renewal potential. The identification of these "leukemia stem cells" (LSCs) provides an additional strategy in treating and preventing relapsed/refractory acute leukemia. One mechanism for resistance to treatment is the protection afforded LSCs via the interaction between stem cell derived growth factor (CXCL-12/SDF-1α) and its receptor, CXCR4. These interactions are implicated in chemotaxis, homing, and survival/apoptosis of hematopoietic stem cells and progenitor cells. All AML and ALL cells express CXCR4 and SDF-1α. AMD3100 (plerixafor, MOBOZIL®) is a bicyclam that blocks CXCL-12 binding to and signaling through CXCR4, thus disrupting tumor-stroma interactions and mobilizing leukemia cells from their protective stromal environment. Plerixafor is currently FDA approved for use in stem cell mobilization for autologous transplantation in hematologic malignancies. Clinical trials in adult patients with relapsed AML have demonstrated promising results when combining plerixafor with cytotoxic chemotherapy.

This Phase I clinical trial will be the first to test the concept of a "chemosensitization" approach in children using Plerixafor. Patients aged 3 to 30 with relapsed/refractory AML, ALL or MDS will receive Plerixafor followed 4 hours later with combination chemotherapy consisting of etoposide and cytarabine daily for five days. We will determine the safety and tolerability of Plerixafor in combination with cytarabine and etoposide in pediatric and young adults with relapsed/refractory acute leukemias. The secondary objectives of this study will quantify the peripheral blood mobilization of blasts in response to Plerixafor using flow cytometry, measure initial CXCR4 expression on leukemic blasts and correlate with response, and determine the change in CXCR4 expression after protocol therapy. Finally, we will determine the pharmacokinetics of Plerixafor when administered with cytotoxic chemotherapy in this patient population.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study Using Plerixafor as a Chemosensitizing Agent for Relapsed Acute Leukemia and MDS in Pediatric Patients
Study Start Date : March 2011
Estimated Primary Completion Date : July 2017
Estimated Study Completion Date : July 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia
Drug Information available for: Plerixafor

Arm Intervention/treatment
Experimental: Plerixafor, Dose Escalation
Dose escalation of plerixafor administered intravenously in combination with IV cytarabine and IV etoposide in pediatric patients wtih relapsed/refractory AML/ALL.
Drug: Plerixafor Dose Escalation

Plerixafor dose escalation Dose Level -1 = 3 mg/m2/dose Dose Level 1 = 6 mg/m2/dose Dose Level 2 = 9 mg/m2/dose Dose Level 3 = 12 mg/m2/dose Dose Level 4 = 15 mg/m2/dose

Doses administered 4 hours prior to chemotherapy, then at the same approximate time of day on subsequent days, through the end of that cycle of chemotherapy.

Other Names:
  • AMD3100

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Plerixafor given in combination with chemotherapy [ Time Frame: 6 months post final enrollment ]
    To determine the safety and tolerability of plerixafor in combination with reinduction chemotherapy in pediatric and young adult patients with relapsed/refractory acute leukemia (AML/MDS and ALL)

Secondary Outcome Measures :
  1. Response Rate [ Time Frame: 6 months post completion of treatment for final enrollment ]
    To estimate the response rate, within the context of a Phase I study, of Plerixafor given in sequential combination with cytarabine/etoposide (AE) in patients with relapsed or refractory ALL and AML/MDS.

  2. Pharmacokinetics [ Time Frame: 12 months following last sample collection ]
    To determine the pharmacokinetics of Plerixafor when administered to pediatric and young adult patients with relapsed acute leukemias.

  3. Leukemic blast mobilization [ Time Frame: 12 months after final sample collection ]
    To measure peripheral blood mobilization of leukemic blasts by flow cytometry by comparing blood samples obtained before and after dose 1 of plerixafor, and to correlate degree of mobilization (expressed as % increase in circulating blasts) with response.

  4. CXCR4 expression on leukemic blasts [ Time Frame: 12 months after last patient completes therapy ]
    To measure the quantitative expression of CXCR4 on leukemic blasts at baseline and end of first course of treatment using flow cytometry and qRT-PCR, and correlate expression level with response.

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Ages Eligible for Study:   3 Years to 29 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • >= 3 years of age and <30 years old at study entry
  • diagnosis of relapsed/refractory AML, ALL, secondary AML/MDS, or acute leukemia of ambiguous lineage and meet the following criteria:
  • AML/MDS or leukemia with ambiguous lineage must have >5% blast in bone marrow
  • ALL must have an M3 marrow
  • ALL and AML must not have CNS disease
  • patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy or radiotherapy prior to entering study
  • Karnofsky score >50% for patients >16 years of age and Lansky >50% for patients <= 16 years of age
  • adequate renal and hepatic function as defined in protocol
  • adequate cardiac function as defined in protocol

Exclusion Criteria:

  • ALL and AML patients with CNS disease
  • Absolute blast count greater than 50,000/mcl
  • Systemic fungal, bacterial, viral or other infection without improvement despite appropriate antibiotics or other treatment
  • Significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance
  • Patients who have second cancer, not including secondary AML
  • Patients who are pregnant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01319864

United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
United States, Colorado
The Children's Hospital of Denver
Denver, Colorado, United States, 80045
United States, Georgia
Children's Healthcare of Atlanta/Emory University
Atlanta, Georgia, United States, 30322
United States, Maryland
Johns Hopkins Medical Center
Baltimore, Maryland, United States, 21231
United States, Missouri
The Children's Mercy Hospital and Clinics
Kansas City, Missouri, United States, 64108
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, United States, 17033
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada, T3B 6A8
Sponsors and Collaborators
Seattle Children's Hospital
Children's Healthcare of Atlanta
Pediatric Oncology Experimental Therapeutics Investigation Consortium
Principal Investigator: Todd Cooper, DO Emory University/Children's Healthcare of Atlanta

Additional Information:
Responsible Party: Todd Cooper, Associate Professor, Seattle Children's Hospital Identifier: NCT01319864     History of Changes
Other Study ID Numbers: IRB00047475
POETIC Plerixafor ( Other Identifier: Other )
First Posted: March 22, 2011    Key Record Dates
Last Update Posted: October 19, 2016
Last Verified: October 2016

Keywords provided by Todd Cooper, Seattle Children's Hospital:

Additional relevant MeSH terms:
JM 3100
Acute Disease
Neoplasms by Histologic Type
Disease Attributes
Pathologic Processes
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents