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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase I Study Using Plerixafor as a Chemosensitizing Agent for Relapsed Acute Leukemia and MDS in Pediatric Patients

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.

Detailed Summary:

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 rela
Sponsor: Seattle Children's Hospital

Current Primary Outcome: 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)


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.
  • 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.
  • 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.
  • 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.


Original Secondary Outcome: Same as current

Information By: Seattle Children's Hospital

Dates:
Date Received: March 11, 2011
Date Started: March 2011
Date Completion: July 2017
Last Updated: October 17, 2016
Last Verified: October 2016