Study To Examine Toxicity Of Allogeneic Stem Cell Transplantation For Relapsed Or Therapy Refractory Ewings Sarcoma

NCT02472392 | Completed Phase 1

• 1 other identifier: 13.0167
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

EWINGS SARCOMA

Keywords

EWINGS, SARCOMA

Outcome Measures

Primary Outcomes (1)

• Toxicity assessed by safety labs and close monitoring from the study staff

  This will be assessed by safety labs and close monitoring from the study staff.

  Over 5 Years

Study Arms (2)

Treatment Plan A

ACTIVE COMPARATOR

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; Drug: Busulfan; Drug: Melphalan

Treatment Plan B

ACTIVE COMPARATOR

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; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

Rabbit anti-thymocyte globulin DRUG

Active treatment

Also known as: ATG, thymoglobulin

Treatment Plan A; Treatment Plan B

Busulfan DRUG

comparitor

Also known as: Busulfex, Myleran

Treatment Plan A

Melphalan DRUG

comparitor

Also known as: L-PAM, L-Sarcolysin, Phenylalanine Mustard

Treatment Plan A

Fludarabine DRUG

comparitor

Also known as: Fludara

Treatment Plan B

Cyclophosphamide DRUG

comparitor

Also known as: Cytoxan, Neosar

Treatment Plan B

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• University of Louisville: lead

Study Sites (1)

University of Louisville

Louisville, Kentucky, 40202, United States

Location

MeSH Terms

Conditions

Sarcoma, Ewing

Interventions

Antilymphocyte Serum; thymoglobulin; Busulfan; Melphalan; fludarabine; fludarabine phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds

Study Officials

• Kenneth Lucas, M.D.

  University of Louisville

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2015
• First Posted: June 15, 2015
• Study Start: April 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: May 9, 2017

Record last verified: 2017-05

Locations

US (1)