- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02472392
Study To Examine Toxicity Of Allogeneic Stem Cell Transplantation For Relapsed Or Therapy Refractory Ewings Sarcoma (Ewing/Allo)
A Phase I Study to Examine the Toxicity of Allogeneneic Stem Cell Transplantation for Relapsed or Therapy Refractory Ewings
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Kentucky
-
Louisville, Kentucky, United States, 40202
- University of Louisville
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
- 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:
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]
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Active treatment
Other Names:
comparitor
Other Names:
comparitor
Other Names:
|
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.
|
Active treatment
Other Names:
comparitor
Other Names:
comparitor
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Over 5 Years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Kenneth Lucas, M.D., University of Louisville
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Osteosarcoma
- Neoplasms, Bone Tissue
- Neoplasms, Connective Tissue
- Sarcoma
- Sarcoma, Ewing
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
- Melphalan
- Fludarabine
- Busulfan
- Thymoglobulin
- Antilymphocyte Serum
Other Study ID Numbers
- 13.0167
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on EWINGS SARCOMA
-
National Cancer Institute (NCI)CompletedNon-Metastatic Ewings SarcomaUnited States
-
University of LouisvilleSolving Kids' CancerCompletedNeuroblastoma | Osteogenic Sarcoma | Rhabdomyosarcoma | Synovial Sarcoma | Ewings SarcomaUnited States
-
Dana-Farber Cancer InstituteChildren's Hospital of Philadelphia; Boston Children's HospitalCompletedNeuroblastoma | Ewings Sarcoma | Non-rhabdomyosarcoma Soft Tissue SarcomaUnited States
-
Gradalis, Inc.CompletedNon Small Cell Lung Cancer | Liver Cancer | Ewings SarcomaUnited States
-
Emory UniversityChildren's Healthcare of AtlantaCompletedRenal Cell Carcinoma | Osteosarcoma | Rhabdoid Tumor | Neuroblastoma | Retinoblastoma | Rhabdomyosarcoma | Wilms Tumor | Hepatoblastoma | Ewings Sarcoma | Non-rhabdomyosarcoma Soft Tissue Sarcoma | Germ Cell Tumors | Clear Cell SarcomaUnited States
-
Albert Einstein College of MedicineNational Cancer Institute (NCI)TerminatedUterine Corpus Leiomyosarcoma | Stage IIA Uterine Sarcoma | Stage IIB Uterine Sarcoma | Stage IIIA Uterine Sarcoma | Stage IIIB Uterine Sarcoma | Stage IIIC Uterine Sarcoma | Stage IVA Uterine Sarcoma | Stage IVB Uterine Sarcoma | Stage IA Uterine Sarcoma | Stage IB Uterine Sarcoma | Stage IC Uterine SarcomaUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)CompletedBone Sarcoma | Retroperitoneal Sarcoma | Adult Soft Tissue SarcomaUnited States
-
National Cancer Institute (NCI)RecruitingMetastatic Alveolar Soft Part Sarcoma | Unresectable Alveolar Soft Part Sarcoma | Advanced Soft Tissue Sarcoma | Advanced Alveolar Soft Part SarcomaUnited States
-
Mohammed M MilhemGenentech, Inc.CompletedSarcoma | Soft Tissue Sarcoma | Metastatic Sarcoma | Locally Advanced Sarcoma | Unresectable SarcomaUnited States
-
National Cancer Institute (NCI)RecruitingMetastatic Leiomyosarcoma | Unresectable Leiomyosarcoma | Metastatic Sarcoma | Unresectable Soft Tissue Sarcoma | Metastatic Soft Tissue Sarcoma | Unresectable SarcomaUnited States
Clinical Trials on Rabbit anti-thymocyte globulin
-
University of CincinnatiGenzyme, a Sanofi CompanyCompletedRenal Transplant Rejection | Transplants and ImplantsUnited States
-
Wright State UniversitySanofi; University of Nebraska; University of Arizona; The Methodist Hospital Research... and other collaboratorsCompletedSafety Trial of Single Versus Multiple Dose Thymoglobulin Induction in Kidney Transplantation (STAT)End-Stage Renal Disease | Kidney FailureUnited States
-
Anhui Provincial HospitalRecruitingSevere Aplastic AnemiaChina
-
Genzyme, a Sanofi CompanyTerminatedMyelodysplastic Syndrome (MDS)Germany, United Kingdom, France, Netherlands
-
The Hospital for Sick ChildrenTerminatedMetabolic Disease | Genetic Disorder | MalignancyCanada
-
Genzyme, a Sanofi CompanyCompletedGraft Rejection | Renal TransplantationUnited States
-
Shanghai General Hospital, Shanghai Jiao Tong University...The First Affiliated Hospital with Nanjing Medical University; The First Affiliated... and other collaboratorsUnknownAcute Lymphoblastic Leukemia | Lymphoblastic LymphomaChina
-
McMaster UniversityCanadian Institutes of Health Research (CIHR); Genzyme, a Sanofi Company; The...UnknownHematologic MalignanciesCanada
-
Genzyme, a Sanofi CompanyCompletedCadaveric Donor Renal Transplantation | Acute Renal Allograft Rejection | Induction TherapyUnited States, France, Spain, United Kingdom, Germany
-
Genzyme, a Sanofi CompanyCompletedAcute Myelogenous Leukemia (AML) | Acute Lymphocytic Leukemia (ALL) | Graft vs. Host Disease (GvHD)United States, Canada