EWINGS SARCOMAPhase 1Ewing/AlloNCT02472392
Study To Examine Toxicity Of Allogeneic Stem Cell Transplantation For Relapsed Or Therapy Refractory Ewings Sarcoma
A Phase 1 study testing Rabbit anti-thymocyte globulin, Busulfan and Melphalan in people with EWINGS SARCOMA, run by University of Louisville at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 30 years
- Conditions the study is for
- EWINGS SARCOMA
- What is being tested?
- Rabbit anti-thymocyte globulin, Busulfan and Melphalan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2013to Dec 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Louisville
Louisville, Kentucky, 40202
About this study
Official title: A Phase I Study to Examine the Toxicity of Allogeneneic Stem Cell Transplantation for Relapsed or Therapy Refractory Ewings
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.
Read the 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.
- Conditions
- EWINGS SARCOMA
- Being tested
- Rabbit anti-thymocyte globulin, Busulfan, Melphalan, Fludarabine, Cyclophosphamide
- Keywords
- EWINGS, SARCOMA
- Medical subject headings
- Sarcoma, Ewing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rabbit anti-thymocyte globulinDrug
Also called ATG, thymoglobulin
Active treatment
BusulfanDrug
Also called Busulfex, Myleran
comparitor
MelphalanDrug
Also called L-PAM, L-Sarcolysin, Phenylalanine Mustard
comparitor
FludarabineDrug
Also called Fludara
comparitor
CyclophosphamideDrug
Also called Cytoxan, Neosar
comparitor
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Rabbit anti-thymocyte globulin; Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Over 5 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2015 (estimated)
- Study startApr 2013
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EWINGS SARCOMAStudies of the same condition, open and under way.
- More trials run by University of LouisvilleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Louisville
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kenneth Lucas, M.D., Principal investigator, University of Louisville
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02472392
- Sponsor's protocol ID
- 13.0167
- Acronym
- Ewing/Allo
- Status last verified
- May 2017
- First submitted
- 4 Jun 2015
- Last updated
- 9 May 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Examine the Toxicity of Allogeneneic Stem Cell Transplantation for Relapsed or Therapy Refractory Ewings
- ClinicalTrials.gov ID
- NCT02472392
- Acronym / sponsor ID
- Ewing/Allo / 13.0167
- Conditions
- EWINGS SARCOMA
- Keywords
- EWINGS, SARCOMA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University of LouisvilleUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 15 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Plan A | Active comparator | Drug: Rabbit anti-thymocyte globulin, Drug: Busulfan, Drug: MelphalanRabbit 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. |
| Treatment Plan B | Active comparator | Drug: Rabbit anti-thymocyte globulin, Drug: Fludarabine, Drug: CyclophosphamideRabbit 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. |
Who may qualify
- Ages
- Up to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (8 listed)
- Organ dysfunction: Patients who have the following levels of organ system dysfunction are not eligible:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rabbit anti-thymocyte globulinAlso: ATG, thymoglobulinActive treatment | Drug | Treatment Plan A, Treatment Plan B |
| BusulfanAlso: Busulfex, Mylerancomparitor | Drug | Treatment Plan A |
| MelphalanAlso: L-PAM, L-Sarcolysin, Phenylalanine Mustardcomparitor | Drug | Treatment Plan A |
| FludarabineAlso: Fludaracomparitor | Drug | Treatment Plan B |
| CyclophosphamideAlso: Cytoxan, Neosarcomparitor | Drug | Treatment Plan B |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth Lucas, M.D. principal investigator
University of Louisville
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Rabbit anti-thymocyte globulin, Busulfan and Melphalan in people with EWINGS SARCOMA, run by University of Louisville at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity assessed by safety labs and close monitoring from the study staff (time frame: Over 5 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2017.