AMD3100 for Sensitizing in Allogeneic Blood or Marrow Transplant for Chemotherapy Resistant Pediatric Acute Leukemia (BMTAMD3100)

This study has been terminated.
(lack of patient enrollment)
Sponsor:
Information provided by (Responsible Party):
Kuang-Yueh Chiang, Emory University
ClinicalTrials.gov Identifier:
NCT01655875
First received: July 27, 2012
Last updated: April 4, 2014
Last verified: April 2014
  Purpose

This study is for patients 2-21 years old who have acute leukemia that has not responded well to chemotherapy and will have a bone marrow transplant. This is a pilot (phase 1) study of AMD3100(also called Plerixafor, Mozobil). AMD3100 is given in combination with a standard pre-transplant conditioning regimen (total body irradiation, etoposide and cyclophosphamide). The conditioning regimen is the treatment that is given just before the transplant. This treatment kills leukemia cells as well as healthy bone marrow and immune cells. Researchers want to learn more about how AMD3100 affects acute leukemia cells. Blood and bone marrow samples from study participants will be collected to find out if AMD3100 is making patients' cells more sensitive to the conditioning regimen and to find out how it does this.

The first six patients receive three daily doses (240 mcg/kg via IV). If it appears that three doses do not significantly increase the side effects of transplant conditioning, the investigators will give a second group of six patients five daily doses.


Condition Intervention Phase
Pediatric Acute Myeloblastic Leukemia, Relapsed
Pediatric Acute Lymphoblastic Leukemia, Relapsed
Drug: AMD3100
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of AMD3100 as a Sensitizing Agent in Myeloablative Allogeneic Blood and Marrow Transplantation for Chemotherapy Resistant Pediatric Acute Leukemia

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • AMD3100 safety [ Time Frame: day 42 after bone marrow transplant ] [ Designated as safety issue: Yes ]
    Incidence of grade 3 and 4 regimen-related toxicity assessed per Bearman scale at day 42. Patients in dose level 1 get 3 days of AMD3100. If 2 cases of grade 4 toxicity or 3 cases of grade 3-4 toxicity occur, dose level 1 and study will be closed. Otherwise, after 6 patients have been assessed at day 42, the dose will be escalated to 5 days of AMD3100 (dose level 2). If 2 cases of grade 4 toxicity or 3 cases of grade 3-4 toxicity occur, the study will be closed. Otherwise, after 6 patients have been enrolled at this level the study will be closed to enrollment.


Secondary Outcome Measures:
  • AMD3100 correlative biology analyses [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Bone marrow and peripheral blood samples collected during study are examined in the laboratory to detect if there is any difference in leukemia cells after treatment with AMD3100.


Enrollment: 1
Study Start Date: June 2012
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: bone marrow transplant Drug: AMD3100
AMD3100 will first be administered at 240 mcg/kg (the FDA approved dose for mobilization of autologous PBSC) IV once daily prior to conditioning for 3 days (days -6, -5 and -4) in the first group of participants. If toxicity criteria are met, the dosing will be escalated in the second group of participants to 240 mcg/kg IV once daily prior to conditioning for 5 days (days -8, -7, -6, -5 and -4).
Other Names:
  • Mozobil
  • Plerixafor

Detailed Description:

The first six patients will receive three daily doses of AMD3100 (240 mcg/kg via IV). If it appears that three doses do not significantly increase the side effects of transplant conditioning, the investigators will give a second group of six patients five daily doses.

AMD3100 is given in combination with a standard pre-transplant conditioning regimen (total body irradiation, etoposide and cyclophosphamide.) AMD3100 causes healthy bone marrow cells to be released from the bone marrow into the blood so that they can be collected in patients who will have peripheral (blood stream) blood stem cell transplants. AMD3100 also pushes out leukemia cells from the bone marrow. Research in animals and in test tubes shows that the bone marrow partially protects leukemia cells from chemotherapy and radiation. AMD3100 could make leukemia treatments better by pushing out the leukemia cells from the bone marrow and making them more sensitive to treatment. Clinical trials combining AMD3100 with normal doses of chemotherapy are being done for relapsed acute leukemia. Researchers hope AMD3100 can be given with conditioning regimen safely without causing more side effects. Up to 12 participants will be enrolled and estimated accrual duration is 2 years.

  Eligibility

Ages Eligible for Study:   2 Years to 22 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have chemotherapy-resistant acute leukemia (primary refractory or relapsed and refractory AML, ALL, undifferentiated, bi-lineage or mixed lineage leukemia)
  • Participant must have a well HLA matched related, mismatched related or unrelated marrow donor with whom the patient is allele matched at at least 7 of 8 HLA loci or a single unrelated cord blood unit matched at at least 4 of 6 HLA loci with minimal dose of 4x10(7)NC/Kg

Exclusion Criteria:

  • Prior allogeneic or autologous hematopoietic stem cell transplantation
  • Prior exposure to AMD3100
  • Active central nervous system leukemia
  • Uncontrolled viral, bacterial, fungal, protozoal infection
  • HIV infection
  • Does not meet standard organ function for transplant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01655875

Locations
United States, Georgia
Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Kuang-Yueh Chiang, MD, PhD Emory University
  More Information

No publications provided

Responsible Party: Kuang-Yueh Chiang, Associate Professor, Emory University
ClinicalTrials.gov Identifier: NCT01655875     History of Changes
Other Study ID Numbers: IRB00053638, CHOA AMD3100 Pilot
Study First Received: July 27, 2012
Last Updated: April 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
Allogeneic Blood and Marrow Transplantation

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
JM 3100
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014