Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Myeloablative Hematopoietic Progenitor Cell Transplantation (HPCT) for Pediatric Malignancies

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2011 by Ann & Robert H Lurie Children's Hospital of Chicago
Sponsor:
Information provided by:
Ann & Robert H Lurie Children's Hospital of Chicago
ClinicalTrials.gov Identifier:
NCT00619879
First received: January 8, 2008
Last updated: March 29, 2011
Last verified: March 2011
  Purpose

The purpose of this study is to show that myeloablative hematopoietic progenitor cell transplantation (HPCT) continues to offer acceptable disease-free survival for select patients requiring HPCT.


Condition Intervention Phase
Leukemia, Myelogenous, Chronic
Leukemia, Lymphoblastic, Acute
Leukemia, Myelogenous, Acute
Myeloproliferative-Myelodysplastic Diseases
Lymphoma, Malignant
Drug: Myeloablative Chemotherapy Regimen for Lymphoid Malignancies or Cord Blood Unit Recipients
Drug: Myeloablative Chemotherapy Regimen for Non-Cord Blood Unit Recipients with Myeloid Malignancies
Other: Hematopoietic Progenitor Cell Transplantation (HPCT)
Radiation: CNS radiation treatment for ALL with prior CNS disease patients
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Myeloablative Hematopoietic Progenitor Cell Transplantation (HPCT) for Pediatric Malignancies

Resource links provided by NLM:


Further study details as provided by Ann & Robert H Lurie Children's Hospital of Chicago:

Primary Outcome Measures:
  • Evaluate the morbidity and mortality of hematopoietic progenitor cell transplantation (HPCT) at Children's Memorial Hospital. [ Time Frame: To study end ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate the effectiveness of graft versus host disease prevention with a combination of anti-thymocyte globulin, continuous infusion cyclosporine, and short course methotrexate for transplants. [ Time Frame: To study end ] [ Designated as safety issue: Yes ]
  • Determine the toxicity of a single conditioning regimen consisting of total body irradiation, etoposide, and Cyclophosphamide for patients with transplant eligible lymphoid malignant conditions or myeloid malignant conditions receiving cord blood units. [ Time Frame: To study end ] [ Designated as safety issue: Yes ]
  • Determine the toxicity of a single conditioning regimen consisting of Busulfan and Cyclophosphamide for patients with transplant eligible myeloid malignant conditions who are not receiving cord blood units. [ Time Frame: To study end ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
Study Start Date: March 2007
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Myeloablative Chemotherapy Regimen for Lymphoid Malignancies or Cord Blood Unit Recipients

    Total Body Irradiation (TBI) 1200 cGy will be given on days -8,-7,-6 and -5 in eight sessions, delivering 150cGy in each session.

    Etoposide 1000 mg/m2 as a 24 hour continuous infusion started on day -4.

    Cyclophosphamide 60 mg/kg/day IV given over 1 hour daily on days -3, -2.

    Drug: Myeloablative Chemotherapy Regimen for Non-Cord Blood Unit Recipients with Myeloid Malignancies

    Busulfan administration:

    • For children >/= 4 years of age, Busulfan 0.8 mg/kg/dose will be given every 6 hours over days -8,-7, -6, and -5 for a total of 16 doses.
    • For children < 4 years of age, Busulfan 1 mg/kg/dose will be given every 6 hours over days -8, -7, -6, -5 for a total of 16 doses.
    • Pharmacokinetic analysis will guide dose modifications targeted to receive an average AUC of 800-1200 microMols*min for the 16 doses.

    Lorazepam (0.05 mg/kg) IV will be administered one half hour before the initial dose of Busulfan is given and every 6 hours through day -4.

    Etoposide 1000 mg/m2 as a 24 hour continuous infusion started on day -4.

    Cyclophosphamide 60 mg/kg/day IV given over 1 hour daily on days -3 and -2.

    Other: Hematopoietic Progenitor Cell Transplantation (HPCT)
    Hematopoietic progenitor cells (HPCs) will be infused on day 0. Source of cells may be bone marrow, peripheral blood cells, or cord blood units, from matched related or unrelated donors.
    Radiation: CNS radiation treatment for ALL with prior CNS disease patients

    Patients with prior CNS disease over the age of 1 year will be treated with 600 cGy of cranial irradiation in addition to 1200 cGy of TBI.

    Patients diagnosed with ALL with CNS disease (at the time of diagnosis or relapse) < 1 year of age will receive CNS treatment as Intrathecal Methotrexate as follows:

    • Infants ≤ 1 year of age at the time of Intrathecal Therapy will receive a dosing of 7.5 mg once a month for 6 months after transplant beginning at day +30 with an adequate white count
    • Children 1-2 years of age at the time of Intrathecal Therapy will receive 8 mg once a month for 6 months after transplant beginning at day +30 with an adequate white count
Detailed Description:

Myeloablative hematopoietic progenitor cell transplantation (HPCT) remains the standard of care for patients requiring HPCT. The purpose of this study is to evaluate the morbidity and mortality of myeloablative HPCT at Children's Memorial Hospital. It will also look to determine the toxicity of a single conditioning regimen consisting of total body irradiation (TBI), etoposide (VP-16), and Cyclophosphamide for patients with transplant eligible lymphoid malignant conditions or with transplant eligible myeloid malignant conditions who are receiving cord blood units, or to determine the toxicity of a single conditioning regimen consisting of Busulfan and Cyclophosphamide for patients with transplant eligible myeloid malignant conditions who are not receiving cord blood units.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Malignant Disease

    • Chronic myleogenous leukemia in chronic or accelerated phase
    • Acute lymphoblastic leukemia (ALL)

      • First remission high-risk ALL (Ph+, t( 4-11) infants).
      • Second remission ALL, after a short first remission (<36 mos from Dx).
      • 3rd or greater remission ALL.
    • Acute myelogenous leukemia (AML)

      • First remission high risk acute nonlymphoblastic (ANLL) (as defined by cytogenetics), if a matched sibling donor is available.
      • Initial partial remission AML (<20% blasts in the bone marrow).
      • AML that is refractory to two cycles of induction therapy.
      • Second or greater remission AML
    • Myelodysplastic/Myeloproliferative Disease

      • Juvenile Myelomonocytic Leukemia (JMML)
      • Myelosplastic syndrome and/or pre-leukemia at any stage
    • Lymphoma

      • Relapsed lymphoma with residual disease that appears to be chemo-sensitive and non-bulky (<5 cm at largest diameter)
  • Venous Access: Three lumens of central vascular access will be required for all patients entered on protocol due to the need for a dedicated line for continuous infusion cyclosporine.
  • Informed Consent: The patient and/or the patient's legally authorized guardian must acknowledge in writing that consent to become a study subject has been obtained in accordance with the institutional policies approved by the U.S. Department of Health and Human Services.
  • Patient organ function requirements:

    • Adequate renal function: Serum Creatinine <~1.5 x normal, or Creatinine clearance of 70 mL/min/1.73 mE2 or an equivalent GFR as determined by the institutional normal range
    • Adequate liver function: Total bilirubin <1.5 x normal; and SGOT (AST) or SGPT (ALT) <~2.5 x normal
    • Adequate cardiac function: Shortening fraction of >/=27% by echocardiogram
    • Adequate pulmonary function: FEV1/FVC >/=60% by pulmonary function test; for children who are uncooperative, no evidence of dysnpea at rest, or exercise intolerance, and must have a pulse oximetry >94% in room air
  • Performance status: Lansky for children </= 16 years >/= 60; Karnofsky status for those > 16 years of age >/= 70
  • Effective Contraceptive Use: Women of childbearing potential and sexually active males should use effective contraception while on study.

Exclusion Criteria:

  • Patients who are pregnant or lactating
  • Inability to find a suitable donor for the patient
  • Patient is HIV-positive
  • Patient has active Hepatitis B
  • Disease progression or relapse prior to HPC infusion
  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: NCT00619879

Contacts
Contact: Morris Kletzel, MD 773-880-4562 mkletzel@northwestern.edu
Contact: Terriss Conterato 773-880-8153 TConterato@childrensmemorial.org

Locations
United States, Illinois
Children's Memorial Hospital Recruiting
Chicago, Illinois, United States, 60614
Principal Investigator: Morris Kletzel, MD         
Sponsors and Collaborators
Ann & Robert H Lurie Children's Hospital of Chicago
Investigators
Principal Investigator: Morris Kletzel, MD Ann & Robert H Lurie Children's Hospital of Chicago
  More Information

No publications provided

Responsible Party: Morris Kletzel, MD, Children's Memorial Hospital
ClinicalTrials.gov Identifier: NCT00619879     History of Changes
Other Study ID Numbers: SCT 0307
Study First Received: January 8, 2008
Last Updated: March 29, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Ann & Robert H Lurie Children's Hospital of Chicago:
Leukemia, Myelogenous, Chronic
Leukemia, Lymphoblastic, Acute
Leukemia, Myelogenous, Acute
Juvenile Myelomonocytic Leukemia
Myeloproliferative-Myelodysplastic Diseases
Dysmyelopoietic Syndromes
Lymphoma, Malignant
Stem Cell Transplantation, Hematopoietic
Allogeneic Transplantation
Human Leukocyte Antigens
Busulfan
Total Body Irradiation
VP-16
Etoposide
Cyclophosphamide
Graft-Versus-Host Disease

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma
Lymphoma, Non-Hodgkin
Bone Marrow Diseases
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014