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Study To Examine Toxicity Of Allogeneic Stem Cell Transplantation For Relapsed Or Therapy Refractory Ewings Sarcoma (Ewing/Allo)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Louisville
ClinicalTrials.gov Identifier:
NCT02472392
First received: June 4, 2015
Last updated: May 8, 2017
Last verified: May 2017
  Purpose
The purpose of this study is to examine the toxicity of using allogeneic stem cell transplantation for treatment of subjects with relapsed or refractory ES and rhabdomyosarcoma. This is a nanrandomized two-arm study is designed to determine the safety and incidence of graft versus host disease (GVHD) in patients with relapsed, refractory Ewings sarcoma receiving related and unrelated, allogeneic stem cell transplants.

Condition Intervention Phase
EWINGS SARCOMA Drug: Rabbit anti-thymocyte globulin Drug: Busulfan Drug: Melphalan Drug: Fludarabine Drug: Cyclophosphamide Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study to Examine the Toxicity of Allogeneneic Stem Cell Transplantation for Relapsed or Therapy Refractory Ewings

Resource links provided by NLM:


Further study details as provided by University of Louisville:

Primary Outcome Measures:
  • Toxicity assessed by safety labs and close monitoring from the study staff [ Time Frame: Over 5 Years ]
    This will be assessed by safety labs and close monitoring from the study staff.


Estimated Enrollment: 10
Study Start Date: April 2013
Study Completion Date: December 2016
Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Treatment Plan A
Rabbit anti-thymocyte globulin (ATG) will be given only to unrelated donor transplant recipients at a dose of 3 mg/kg/day I.V. Equine ATG at a dose of 30mg/kg/day may be substituted in the event of severe allergic reaction to the rabbit ATG. Rabbit ATG is only used with recipients of unrelated donor marrow or peripheral blood transplants. Busulfan (BU) will be given at a dose of 0.8 mg/kg IV q 6 hrs. BU doses will be modified based upon pharmacokinetics data to maintain steady state levels of 600-900 ng/dl. Seizure prophylaxis with levetiracetam should begin prior to the 1st dose of BU and stoped 24 hrs after the last dose of BU. Melphalan will be given at a dose of 60 mg/m2 I.V. over 15-20 min per Pediatric SCT Standards of Practice Manual.
Drug: Rabbit anti-thymocyte globulin
Active treatment
Other Names:
  • ATG
  • thymoglobulin
Drug: Busulfan
comparitor
Other Names:
  • Busulfex
  • Myleran
Drug: Melphalan
comparitor
Other Names:
  • L-PAM
  • L-Sarcolysin
  • Phenylalanine Mustard
Active Comparator: Treatment Plan B
Rabbit anti-thymocyte globulin (ATG) will be given only to unrelated donor transplant recipients at a dose of 3 mg/kg/day I.V. Equine ATG at a dose of 30mg/kg/day may be substituted in the event of severe allergic reaction to the rabbit ATG. Rabbit ATG is only used with recipients of unrelated donor marrow or peripheral blood transplants. Fludarabine will be given at a dose of 30 mg/m2/day IV over 30 mins for 5 doses. Cyclophosphamide will be given at a dose of 50 mg/kg/day IV over 2 hrs for 4 doses.
Drug: Rabbit anti-thymocyte globulin
Active treatment
Other Names:
  • ATG
  • thymoglobulin
Drug: Fludarabine
comparitor
Other Name: Fludara
Drug: Cyclophosphamide
comparitor
Other Names:
  • Cytoxan
  • Neosar

Detailed Description:

This study will examine the toxicity of using allogeneic stem cell transplantation for treatment of subjects with relapsed or refractory ES and rhabdomyosarcoma. Donors will consist of either HLA identical or 9/10 (A, B, C, DR, DQ) matched related or unrelated donors. Specifically, we will examine the toxicity of allogeneic stem cell transplant (SCT) in this patient population, as related to incidence of grade 3-4 acute GVHD and the incidence of transplant related mortality at 100 days by using the following treatment plans.

Rabbit anti-thymocyte globulin (ATG; thymoglobulin) will be given only to unrelated donor transplant recipients at a dose of 3 mg/kg/day I.V. for 3 consecutive days (Days -8 to-6). Equine ATG at a dose of 30mg/kg/day may be substituted in the event of severe allergic reaction to the rabbit ATG.

Busulfan (BU) will be given at a dose of 0.8 mg/kg IV q 6 hours, for 16 doses on days -8 through -5. Busulfan doses will be modified based upon pharmacokinetics data to maintain steady state levels of 600-900 ng/dl. Patients should start seizure prophylaxis with levetiracetam prior to the first dose of busulfan and discontinued 24 hours after the last dose of busulfan.

Melphalan will be given at a dose of 60 mg/m2 I.V. over 15-20 min on days -4 through -2 as per Pediatric SCT Standards of Practice Manual.

Fludarabine will be given at a dose of 30 mg/m2/day IV over 30 minutes for 5 doses on days -8 through -4.

Cyclophosphamide will be given at a dose of 50 mg/kg/day IV over 2 hours for 4 doses on days -5 through -2.

Subjects will receive tacrolimus and short course mycophenolate for prohpylactic Therapy incase of Acute Graft-versus-Host Disease.

The following procedures will also be completed throughout this study.

Physical exams and medical histories Frequent blood tests to monitor blood counts, blood chemistries, liver and kidney function Blood tests to determine exposure to various viruses, including viruses that cause hepatitis (inflammation of the liver), the human immunodeficiency virus (HIV, the virus that causes AIDS) and cytomegalovirus Pregnancy test for females of childbearing age Bone Marrow biopsies and aspirates Tests to monitor lung and heart function Evaluations and biopsies to monitor GVHD X-rays, CT or MRI scans for tumor measurements at 1, 3, 6 and 12 months and then at least annually thereafter.

If subjects agree to participate in this research study, they will receive several drugs before the SCT. Various methods will be used to administer medications such asPO, IV, or Central Line placement.

  Eligibility

Ages Eligible for Study:   up to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients aged 0-30 years with relapsed or therapy refractory ES, excluding patients with brain metastases. Patients who have received a prior autologous stem cell transplant are eligible.
  2. Related and unrelated marrow and peripheral blood stem donors must be 9/10 or 10/10 (HLA A, B, C, DR, DQ) matched with the recipient

Exclusion Criteria:

  1. Organ dysfunction: Patients who have the following levels of organ system dysfunction are not eligible:

    • Cardiac: Ejection Fraction < 50 %
    • Renal: Est. Creatinine Clearance < 50*
    • Hepatic: Bilirubin > 3.0
    • Pulmonary: DLCO < 70 %, or for patient who cannot cooperate with pulmonary function testing, O2 saturation < 95 % on room air.
    • Performance status: Lansky performance < 70; ECOG status > 2 *this is based on the Schwartz formula for children less than 18 years of age, and the Cockcroft - Gault formula, for those > 18 years.[21, 22]
  2. Patients with an isolated local recurrence of their tumor (in the site of the primary tumor) > 1 year after completing therapy are excluded, as these patients could be cured with local therapy alone.

3 As a part of the standard of care for pre-transplant evaluation, subjects will be tested for exposure to viral agents such as hepatitis B, C, HTLV-1/2, and HIV. Subjects testing positive for HIV may be rejected as candidates for transplantation, based on the clinical judgment of the stem cell transplant physician

  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: NCT02472392

Locations
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
Sponsors and Collaborators
University of Louisville
Investigators
Principal Investigator: Kenneth Lucas, M.D. University of Louisville
  More Information

Responsible Party: University of Louisville
ClinicalTrials.gov Identifier: NCT02472392     History of Changes
Other Study ID Numbers: 13.0167
Study First Received: June 4, 2015
Last Updated: May 8, 2017

Keywords provided by University of Louisville:
EWINGS, SARCOMA

Additional relevant MeSH terms:
Sarcoma
Sarcoma, Ewing
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Cyclophosphamide
Fludarabine phosphate
Melphalan
Busulfan
Antilymphocyte Serum
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on August 18, 2017