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CompletedNCT00043979Updated May 31, 2017Results posted

Stem Cell Transplantation in Patients With High-Risk and Recurrent Pediatric Sarcomas

A Phase 2 interventional study of F-18 Fluorodeoxyglucose and therapeutic allogeneic lymphocytes in Sarcoma, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 5 Years to 35 Years. Per ClinicalTrials.gov, last updated 2017-05-31.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
60
Allocation
Non-randomized
Ages
5 Years to 35 Years
Sex
All
01

Study summary

This study will examine the safety and effectiveness of stem cell transplantation for treating patients with sarcomas (tumors of the bone, nerves, or soft tissue). Stem cells are immature cells in the bone marrow and blood stream that develop into blood cells. Stem cells transplanted from a healthy donor travel to the patient's bone marrow and begin producing normal cells. In patients with certain cancers, such as leukemia and lymphoma, the donor's immune cells attack the patient's cancer cells in what is called a "graft-versus-tumor" effect, contributing to cure of the disease. This study will determine whether this treatment can be used successfully to treat patients with sarcomas.

Patients between 4 and 35 years of age with a sarcoma that has spread from the primary site or cannot be removed surgically, and for whom effective treatment is not available, may be eligible for this study. Candidates must have been diagnosed by the age of 30 at the time of enrollment. They must have a matched donor (usually a sibling). Participants undergo the following procedures:

Donors: Stem cells are collected from the donor. To do this, the hormone granulocyte colony stimulating factor (G-CSF) is injected under the skin for several days to move stem cells out of the bone marrow into the bloodstream. Then, the cells are collected by apheresis. In this procedure the blood is drawn through a needle placed in one arm and pumped into a machine where the stem cells are separated out and removed. The rest of the blood is returned to the donor through a needle in the other arm.

Patients: For patients who do not already have a central venous catheter (plastic tube), one is placed into a major vein. This tube can stay in the body the entire treatment period for giving medications, transfusing blood, , withdrawing blood samples, and delivering the donated stem cells. Before the transplant procedure, patients receive from one to three cycles of "induction" chemotherapy, with each cycle consisting of 5 days of fludarabine, cyclophosphamide, etoposide, doxorubicin, vincristine, and prednisone followed by at least a 17-day rest period. All the drugs are infused through the catheter except prednisone, which is taken by mouth. After the induction therapy, the patient is admitted to the hospital for 5 days of chemotherapy with high doses of cyclophosphamide, melphalan, and fludarabine. Two days later, the stem cells are infused. The anticipated hospital stay is about 3 weeks, but may be longer if complications arise. Patients are discharged when their white cell count is near normal, they have no fever or infection, they can take sufficient food and fluids by mouth, and they have no signs of serious graft-versus-host disease (GVHD)-a condition in which the donor's cells "see" the patient's cells as foreign and mount an immune response against them.

After hospital discharge, patients are followed in the clinic at least once or twice weekly for a medical history, physical exam, and blood tests for 100 days. They receive medications to prevent infection and GVHD and, if needed, blood transfusions. If GVHD has not developed by about 120 days post transplant, patients receive additional white cells to boost the immune response. After 100 days, follow-up visits may be less frequent. Follow-up continues for at least 5 years. During the course of the study, patients undergo repeated medical evaluations, including blood tests and radiology studies, to check on the cancer and on any treatment side effects. On four occasions, white blood cells may be collected through apheresis to see if immune responses can be generated against the sarcomas treated in this study. Positron emission tomography (PET) scans may be done on five occasions. This test uses a radioactive material to produce images useful in detecting primary tumors and cancer that has spread.

Read the detailed description

Background:

  • Treatment of pediatric sarcomas has enjoyed progress in the past 25 years for patients with localized, chemosensitive disease and prognostic factors are now available to identify subsets of patients who have very dismal prognoses; patients with primary metastatic disease, especially those with bone and bone marrow metastases.
  • Patients with primary chemoresistant disease and early recurrence also have very poor prognoses and lack suitable treatment options. For these patients, it is critical that alternative approaches to cytotoxic chemotherapy be identified.
  • Basic laboratory studies have shown that Ewing's sarcoma is susceptible to immune mediated mechanisms of cytolysis in vitro. Interestingly, for Ewing's sarcoma this appears to be true for both chemosensitive and chemoresistant cell lines.
  • Recent progress in the field of bone marrow transplantation has identified approaches that can reproducibly induce allogeneic peripheral blood stem cell engraftment in adults with hematologic malignancies. In some cases, this same approach has shown beneficial effects for patients with solid tumors as a result of the development of allogeneic, immune-mediated graft versus tumor effects.

Objectives:

  • To determine if the transplantation of human leukocyte antigen (HLA) matched, peripheral blood stem cells can result in full donor engraftment (greater than 95 percent by day 100) in patients with high risk-pediatric sarcomas.
  • To identify and characterize the toxicities of HLA-matched peripheral blood stem cell transplant (PBSCT) in patients with high-risk pediatric sarcomas. In particular we will identify the incidence of graft versus host disease (GVHD) and the pace of immune reconstitution in this population.
  • To determine if allogeneic graft-versus-tumor responses following allogeneic PBSCT can induce clinically significant anti-tumor effects as measured by radiographic evidence of antitumor responses following PBSCT in patients with measurable disease and improved clinical outcome compared to historical controls in this patient population with a universally poor outcome.

Eligibility:

  • Patients, age of greater than 4 years at enrollment to less than 30 years at diagnosis and age less than 35 at enrollment, with ultra-high risk Ewing's sarcoma family of tumors, desmoplastic small round cell tumor or alveolar rhabdomyosarcoma.
  • Patients must have completed standard front-line therapy and salvage therapy.
  • Patient must have the availability of a 5 or 6 antigen HLA-matched first-degree relative donor or a genotypically identical twin.
  • Patients must have adequate cardiac, pulmonary, renal, liver, and marrow function.

Design:

-Donor will be prepared for peripheral blood stem cell harvest with Filgrastim mobilization, 10 microg/kg per day subcutaneous (SQ) for 5-7 days until they have stem cell collected by apheresis. The stem cells will then be cryopreserved.

Patients will receive 1 to 3 21 day cycles of Fludarabine-EPOCH induction chemotherapy. The preparative regimen will consist of cyclophosphamide, fludarabine and melphalan followed by stem cell infusion. GVHD prophylaxis will consist of sirolimus and tacrolimus.

02

Conditions studied

  • Sarcoma

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Keywords

  • Ewing's Sarcoma
  • Rhabdomyosarcoma
  • Desmoplastic Small Round Cell Tumor
  • Sarcoma
  • Ewing Sarcoma
03

In context

Sarcoma

1,667 studies on the registry are indexed under Sarcoma; 393 are open to participants now.

This study's enrollment of 60 is above the median of 40 across 1,283 interventional studies indexed under Sarcoma.

Browse Sarcoma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
5 Years to 35 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

  • INCLUSION CRITERIA: PATIENT

The following diagnoses will be considered:

  1. Patients with Ewing's sarcoma family of tumors, or alveolar

    rhabdomyosarcoma in one of the following categories:

    • Patients who present at the time of initial diagnosis with bone or bone marrow metastases may be enrolled after completion of standard front-line therapy. Standard front line therapy for alveolar rhabdomyosarcoma should include vincristine and cyclophosphamide, plus actinomycin D and/or adriamycin. For patients with Ewing's sarcoma, standard front line therapy should include vincristine, cyclophosphamide, adriamycin, ifosfamide and etoposide.
    • Patients with recurrence of tumor at any site less than one year after completing standard front-line therapy or with a second or subsequent recurrence at any time after completing standard front-line therapy.
    • Patients with progression or persistence of disease while receiving standard front-line chemotherapy who cannot achieve a complete response (CR) with local treatment modalities.

  2. The following patients with desmoplastic small round cell tumor are eligible after receiving front line standard therapy, which is defined as a regimen containing at least vincristine, cyclophosphamide, and adriamycin:

    • unresectable disease
    • metastatic tumor (abdominal and extra-abdominal disease)
    • progressive or persistent while receiving standard therapy

    • recurrence within one year of completing therapy

      • Patients without evaluable tumor at the time of enrollment are eligible
      • Patients who have previously received high-dose chemotherapy with autologous stem cell rescue are eligible for this trial.
      • Patient age 5-35 at enrollment.
      • Availability of a 5 or 6 antigen human leukocyte antigen (HLA)-matched first-degree relative donor (single HLA-A or B mismatch allowed). Genotypically identical twins may serve as stem cell donors. Genotypic identity must be confirmed by restrictive fragment length polymorphism (RFLP) analysis.
      • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 or, for children less than or equal 10 years of age, Lansky greater than or equal 60
      • Cardiac function: Left ventricular ejection fraction greater than or equal to 45% by multi-gated acquisition scan (MUGA), fractional shortening greater than or equal 28% by echocardiogram (ECHO) or left ventricular ejection fraction greater than or equal 55% by ECHO.
      • Pulmonary function: carbon monoxide diffusing capacity (DLCO) greater than or equal to 50% of the expected value corrected for alveolar volume.
      • Renal function: Age-adjusted normal serum creatinine according to the following table or a creatinine clearance greater than or equal to 60 ml/min/1.73 m\^2. Age (years) Maximum serum creatinine (mg/dl) less than or equal to 5 0.8 greater than 5, less than or equal to 10 1.0 greater than 10, less than or equal to15 1.2, greater than 15 1.5
      • Liver function: Serum total bilirubin less than 2 mg/dl, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 times upper limit of normal.
      • Marrow function: absolute neutrophil count (ANC) must be greater than 750/mm\^3 (unless due to underlying disease in which case there is no grade restriction), platelet count must be greater than or equal to 75,000/mm\^3 (not achieved by transfusion) unless due to underlying disease in which case there is no grade restriction). Lymphopenia, cluster of differentiation 4 (CD4) lymphopenia, leukopenia, and anemia will not render patients ineligible.
      • Ability to give informed consent. For patients less than18 years of age their legal guardian must give informed consent. Pediatric patients will be included in age appropriate discussion in order to obtain verbal assent.
      • Durable power of attorney form completed (patients greater than or equal to18 years of age only).

INCLUSION CRITERIA: DONOR

  • Weight greater than or equal 15 kilograms.
  • First degree relative with genotypic identity at 5 or 6 HLA loci (single HLAA or B locus mismatch allowed). Genotypically identical twins may serve as stem cell donors. Genotypic identity must be confirmed by RFLP analysis.
  • For donors less than 18 years of age, he/she must be the oldest suitable donor, their legal guardian must give informed consent, the donor must give verbal assent, and he/she must be cleared by social work and a mental health specialist to participate.
  • For donors greater than or equal to 18 years of age, ability to give informed consent.
  • Adequate peripheral venous access for apheresis or consent to use a temporary central venous catheter for apheresis.
  • Donor selection criteria will be in accordance with National Institutes of Health (NIH)/Clinical Center (CC) Department of Transfusion Medicine Standards.

EXCLUSION CRITERIA: PATIENT

  • Uncontrolled fungal infection.
  • History of untreated CNS tumor involvement. Extradural masses which have not invaded the brain parenchyma (as is commonly observed in Ewing's sarcoma family of tumors) or parameningeal tumors (as is commonly observed in rhabdomyosarcoma) without evidence for leptomeningeal spread will not render the patient ineligible. Patients with previous central nervous system (CNS) tumor involvement that has been treated and has been stable for at least 6 weeks are eligible.
  • Lactating or pregnant females.
  • Human immunodeficiency virus (HIV) positive (due to unacceptable risk following allogeneic transplantation).
  • Hepatitis B surface antigen (HBsAg) positive or hepatitis C antibody positive with elevated liver transaminases. All patients with chronic active hepatitis (including those on treatment) are ineligible.
  • High risk of inability to comply with transplant protocol, or inability to give appropriate informed consent in the estimation of the principal investigator (PI), social work, or the stem cell transplant team.
  • Fanconi Anemia

EXCLUSION CRITERIA: DONOR

  • History of medical illness which poses a risk to donation in the estimation of the PI or the Department of Transfusion Medicine physician including, but not limited to stroke, hypertension that is not controlled with medication, or heart disease. Individuals with symptomatic angina or a history of coronary bypass grafting or angioplasty will not be eligible.
  • History of congenital hematologic, immunologic, oncologic or metabolic disorder, which poses a prohibitive risk to the recipient in the estimation of the PI.
  • Anemia (Hb less than 11 gm/dl) or thrombocytopenia (platelets less than 100,000/micro l).
  • Lactating or pregnant females. Donors of childbearing potential must use an effective method of contraception during the time they are receiving growth colony stimulating factor (G-CSF). The effects of cytokine administration on a fetus are unknown and may be potentially harmful. The effects upon breast milk are also unknown and may potentially be harmful to the infant.
  • Human immunodeficiency virus (HIV)-positive, hepatitis B surface antigen (HBsAg) positive or hepatitis C antibody positive. Donors are providing an allogeneic blood product and there is the potential risk of transmitting these viral illnesses to the recipient.
  • High risk of inability to comply with transplant protocol.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
60 participants (actual)

Study arms

  • Experimental
    Arm 1- Sibling Donors

    Donors (n = 30) were matched first degree relatives who were eligible to donate peripheral blood stem cells.

    Drug: Filgrastim · Procedure: Peripheral Blood Stem Cell donation

  • Experimental
    Arm 2 - Recipients

    Recipients (n=30) were enrolled to receive peripheral blood stem cells (PBSC) and receive either cyclosporine or tacrolimus and sirolimus for graft versus host disease (GVHD) prophylaxis.

    Drug: F-18 Fluorodeoxyglucose · Biological: therapeutic allogeneic lymphocytes · Drug: cyclophosphamide · Drug: cyclosporine · Drug: doxorubicin hydrochloride · Drug: etoposide · Drug: fludarabine phosphate · Drug: melphalan · Drug: prednisone · Drug: sirolimus · Drug: tacrolimus · Drug: vincristine sulfate · Procedure: peripheral blood stem cell transplantation · Drug: Filgrastim

Interventions

  • DrugF-18 Fluorodeoxyglucose

    Also known as: FDG

  • Biologicaltherapeutic allogeneic lymphocytes

    Lymphocyte cells are collected from a healthy donor by apheresis and infused into the patient with a central venous catheter.

  • Drugcyclophosphamide

    Induction - 750 mg/m\^2 intravenous (IV) infusion over 30 minutes x 1 dose. Day 5. Transplant - 1200 mg/m\^2 per day IV infusion over 2 hours daily for 4 days; days -6, -5, -4, -3.

    Also known as: Cytoxan

  • Drugcyclosporine

    6 mg/kg per dose orally every other day (no day 9 dose).

    Also known as: Sandimmune

  • Drugdoxorubicin hydrochloride

    Induction - 10 mg/m\^2 per day continuous intravenous (IV) infusion over 24 hours daily for 4 days. Days 1, 2, 3, 4.

    Also known as: Adriamycin

  • Drugetoposide

    50 mg/m\^2 per day continuous intravenous (IV) infusion over 24 hours daily for 4 days. Days 1, 2, 3, 4.

    Also known as: Vepesid

  • Drugfludarabine phosphate

    Induction - 25 mg/m\^2 per day intravenous (IV) infusion over 30 minutes daily for 3 days. Days 1, 2, 3. Transplant - 30 mg/m\^2 per day IV infusion over 30 minutes daily for 4 days; days -6, -5, -4, -3.

    Also known as: Fludara

  • Drugmelphalan

    Transplant - 100 mg/m\^2 per day intravenous (IV) infusion over 15 minutes for 1 day; day -2.

    Also known as: Alkeran

  • Drugprednisone

    Induction - 60 mg/m\^2 per day in 2-4 divided doses by mouth daily for 5 days; days 1, 2, 3, 4, 5.

    Also known as: Deltasone

  • Drugsirolimus

    Initiated on day +3. Patients \>40kg, the initial dose will be 2 mg every 24 hours orally. Patients \<40 kg, the initial dose will be 1 mg/m\^2.

    Also known as: Rapamune

  • Drugtacrolimus

    Day -1 at least 24 hours before the stem cell infusion at a dose of 0.03 mg/kg/day as a continuous infusion. Twelve hours later oral dose initiated at a dose of 0.1-0.15 mg/kg/day in two divided doses every 12 hours.

    Also known as: Prograf

  • Drugvincristine sulfate

    Induction - 0.4 mg/m\^2 per day continuous intravenous (IV) infusion over 24 hours daily for 4 days; 1, 2, 3, 4.

    Also known as: Oncovin

  • Procedureperipheral blood stem cell transplantation

    Stem cells from a healthy donor are collected and transplanted into the patient using a central venous catheter.

    Also known as: PBSCT

  • DrugFilgrastim
  • ProcedurePeripheral Blood Stem Cell donation
06

What researchers measure

Primary outcomes

  1. Number of Participants With Engraftment

    Engraftment is defined as rapid conversion to complete donor chimerism and is assessed by blood counts and chimerism, \>95% donor engraftment at day 100 in \>75% of patients.

    Time frame: 100 days

  2. Toxicity

    Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

    Time frame: 16.5 months

Secondary outcomes

  1. Number of Participants With Acute and Chronic GVHD

    Acute GVHD as by Modified Glucksberg Criteria occurring before day 100. Chronic GVHD as per Seattle criteria occurring after day 100.

    Time frame: up to 5 years or death

  2. Median Time to Reach Absolute Neutrophil Count of 500/mm(3)

    Days for participants to achieve a neutrophil count of 500/mm(3).

    Time frame: up to 12 days

  3. Median Time to Reach a Platelet Count of 50,000/mm(3)

    Days for participants to achieve a platelet count of 50,000/mm(3).

    Time frame: up to 43 days

  4. Early Post Transplantation Relapse

    Participants who experienced recurrence or progression of disease following transplant.

    Time frame: up to 300 days

  5. Median Progression Free Survival

    Progression free survival was based on the time from on-study date until progression or last follow-up.

    Time frame: up to 77 months

  6. Two Year Survival Rate for Patients Undergoing Allo-Hematopoietic Stem Cell Transplant

    Participants who are alive at two years following Allo-Hematopoietic Stem Cell Transplant.

    Time frame: 2 years

  7. Number of Participants to Complete Conversion to >95% Donor Chimerism

    Participants who tolerated the transplantation regimen and accepted \>95% of the donors blood, marrow, and/or tissue.

    Time frame: up to 30 days

  8. Cluster of Differentiation 4 (CD4) Reconstitution

    The median CD4 count with a range of 85-1565 (absolute count) was used to determine recovery and were considered recovered if in this range. The CD4 count was established by flow cytometry testing.

    Time frame: Day +28-42

  9. Best Response Post-Hematopoietic Stem Cell Transplant EOCH (Etoposide, Vincristine, Cyclophosphamide, and Doxorubicin)

    Response is defined by the Response Evaluation Criteria in Solid Tumors (RECIST). RECIST criteria offer a simplified, conservative, extraction of imaging data for wide application in clinical trials. They presume that linear measures are an adequate substitute for 2-D (dimensional) methods and registers four response categories: Complete response (CR) is disappearance of all target lesions. Partial response (PR) is 30% increase in the sum of the longest diameter of target lesions. Progressive disease (PD) is 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) is small changes that do not meet above criteria. For the purposes of this study very good partial response ((VGPR) is \>75% reduction in disease) was also employed.

    Time frame: up to 10 cycles of therapy or 280 days

  10. Median Survival From Date of Progression

    Median survival from date of progression is based on the time from on-study date until progression or last follow-up.

    Time frame: up to 77 months

Other outcomes

  1. Number of Participants Who Experienced Graft Versus Tumor Effect (GVT)

    GVT is defined as tumor response after day 42 post-transplantation without cytotoxic therapy.

    Time frame: up to day 100

  2. Post-Hematopoietic Stem Cell Transplant (HSCT) Radiotherapy

    Site of radiotherapy (high energy radiation) and/or toxicity experienced by the participants post HSCT radiotherapy. Grading was preformed using the Modified Glucksberg Criteria.

    Time frame: up to 6 cycles or 168 days

07

Results

Posted Sep 13, 2013

Participant flow

Period 1
Participant flow — Period 1
MilestoneSibling DonorsRecipients Cyclosporine GVHD ProphylaxisRecipients Tacrolimus /Sirolimus Prophylaxis
Started301713
Completed231310
Not completed743
Withdrew: Recipient with progressive disease743
Period 2
Participant flow — Period 2
MilestoneSibling DonorsRecipients Cyclosporine GVHD ProphylaxisRecipients Tacrolimus /Sirolimus Prophylaxis
Started01310
Completed01310
Not completed000

Outcome measures

PrimaryNumber of Participants With Engraftment

Engraftment is defined as rapid conversion to complete donor chimerism and is assessed by blood counts and chimerism, \>95% donor engraftment at day 100 in \>75% of patients.

Time frame:
100 days
Reported as:
Number · Participants
Number of Participants With Engraftment
ParticipantsArm 2-Recipients
Number of Participants With Engraftment23
PrimaryToxicity

Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

Time frame:
16.5 months
Reported as:
Number · Participants
Toxicity
ParticipantsArm 2-Recipients
Toxicity30
SecondaryNumber of Participants With Acute and Chronic GVHD

Acute GVHD as by Modified Glucksberg Criteria occurring before day 100. Chronic GVHD as per Seattle criteria occurring after day 100.

Time frame:
up to 5 years or death
Reported as:
Number · participants
Number of Participants With Acute and Chronic GVHD
participantsRecipients -Cyclosporine GVHD ProphylaxisRecipients -Tacrolimus/Sirolimus GVHD Prophylaxis
acute GVHD125
chronic GVHD125
SecondaryMedian Time to Reach Absolute Neutrophil Count of 500/mm(3)

Days for participants to achieve a neutrophil count of 500/mm(3).

Time frame:
up to 12 days
Reported as:
Median · Days
Median Time to Reach Absolute Neutrophil Count of 500/mm(3)
DaysArm 2-Recipients
Median Time to Reach Absolute Neutrophil Count of 500/mm(3)9 (8 to 12)
SecondaryMedian Time to Reach a Platelet Count of 50,000/mm(3)

Days for participants to achieve a platelet count of 50,000/mm(3).

Time frame:
up to 43 days
Reported as:
Median · Days
Median Time to Reach a Platelet Count of 50,000/mm(3)
DaysArm 2-Recipients
Median Time to Reach a Platelet Count of 50,000/mm(3)15 (10 to 43)
SecondaryEarly Post Transplantation Relapse

Participants who experienced recurrence or progression of disease following transplant.

Time frame:
up to 300 days
Reported as:
Median · Days
Early Post Transplantation Relapse
DaysArm 2-Recipients
Early Post Transplantation Relapse100 (28 to 300)
SecondaryMedian Progression Free Survival

Progression free survival was based on the time from on-study date until progression or last follow-up.

Time frame:
up to 77 months
Reported as:
Median · Months
Median Progression Free Survival
MonthsArm 2-Recipients
Median Progression Free Survival15.9 (2.2 to 77.0)
SecondaryTwo Year Survival Rate for Patients Undergoing Allo-Hematopoietic Stem Cell Transplant

Participants who are alive at two years following Allo-Hematopoietic Stem Cell Transplant.

Time frame:
2 years
Reported as:
Number · percentage of participants
Two Year Survival Rate for Patients Undergoing Allo-Hematopoietic Stem Cell Transplant
percentage of participantsArm 2-Recipients
From date of enrollment39.1
From date of transplantation34.8
SecondaryNumber of Participants to Complete Conversion to >95% Donor Chimerism

Participants who tolerated the transplantation regimen and accepted \>95% of the donors blood, marrow, and/or tissue.

Time frame:
up to 30 days
Reported as:
Count of participants · Participants
Number of Participants to Complete Conversion to >95% Donor Chimerism
ParticipantsArm 2-Recipients
Day +1423
Day +2823
SecondaryCluster of Differentiation 4 (CD4) Reconstitution

The median CD4 count with a range of 85-1565 (absolute count) was used to determine recovery and were considered recovered if in this range. The CD4 count was established by flow cytometry testing.

Time frame:
Day +28-42
Reported as:
Median · mm(3)
Cluster of Differentiation 4 (CD4) Reconstitution
mm(3)Arm 2-Recipients
Cluster of Differentiation 4 (CD4) Reconstitution284 (85 to 1042)
SecondaryBest Response Post-Hematopoietic Stem Cell Transplant EOCH (Etoposide, Vincristine, Cyclophosphamide, and Doxorubicin)

Response is defined by the Response Evaluation Criteria in Solid Tumors (RECIST). RECIST criteria offer a simplified, conservative, extraction of imaging data for wide application in clinical trials. They presume that linear measures are an adequate substitute for 2-D (dimensional) methods and registers four response categories: Complete response (CR) is disappearance of all target lesions. Partial response (PR) is 30% increase in the sum of the longest diameter of target lesions. Progressive disease (PD) is 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) is small changes that do not meet above criteria. For the purposes of this study very good partial response ((VGPR) is \>75% reduction in disease) was also employed.

Time frame:
up to 10 cycles of therapy or 280 days
Reported as:
Count of participants · Participants
Best Response Post-Hematopoietic Stem Cell Transplant EOCH (Etoposide, Vincristine, Cyclophosphamide, and Doxorubicin)
ParticipantsArm 2-Recipients
Complete Response (CR)2
Progressive Disease (PD)4
Partial Response (PR)4
Very Good Partial Response (VGPR)2
SecondaryMedian Survival From Date of Progression

Median survival from date of progression is based on the time from on-study date until progression or last follow-up.

Time frame:
up to 77 months
Reported as:
Median · Months
Median Survival From Date of Progression
MonthsArm 2-Recipients
Participants who did not receive a transplant(n=7)3.3 (2.2 to 11.2)
Participants who received a transplant (n=23)19.1 (5.6 to 77.0)
Statistical analysis
  • Arm 2-Recipients · Kaplan-Meier · p = .0003 (7 participants who did not receive a transplant compared with 21 participants transplanted.)
Other pre-specifiedNumber of Participants Who Experienced Graft Versus Tumor Effect (GVT)

GVT is defined as tumor response after day 42 post-transplantation without cytotoxic therapy.

Time frame:
up to day 100
Reported as:
Count of participants · Participants
Number of Participants Who Experienced Graft Versus Tumor Effect (GVT)
ParticipantsArm 2-Recipients
Number of Participants Who Experienced Graft Versus Tumor Effect (GVT)0
Other pre-specifiedPost-Hematopoietic Stem Cell Transplant (HSCT) Radiotherapy

Site of radiotherapy (high energy radiation) and/or toxicity experienced by the participants post HSCT radiotherapy. Grading was preformed using the Modified Glucksberg Criteria.

Time frame:
up to 6 cycles or 168 days
Reported as:
Count of participants · Participants
Post-Hematopoietic Stem Cell Transplant (HSCT) Radiotherapy
ParticipantsArm 2-Recipients
Chest wall; G2 skin1
Abdomen; G4 GI1
Pancreas; G4 LFTs, G4 pancreatitis1
Pleura, mediastinum; G4 LFTs, G2 mucositis1
Chest wall; G4 skin, G3 mucositis1
Spine, skull; G2 nausea+vomiting, G2 fatigue1
Pelvis; G4 enteritis1
Pulmonary (cyberknife)1
Brain; B3 mucositis1
Whole lung; G3 mucositis, G3 skin, G5 lung1
L arm, R shoulder, B/L femur1

Adverse events

Collected over 16.5 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm 2-Recipients29/30 (96.7%)29/30 (96.7%)30/30 (100%)
Most frequent serious events
Showing 10 of 31
Most frequent serious events
EventArm 2-Recipients
Death: Death not associated with CTCAE term: Disease progression NOSGeneral disorders29/30
Gastrointestinal: DiarrheaGastrointestinal disorders2/30
Neurology: SeizureNervous system disorders2/30
Pulmonary/Upper Respiratory: Dyspnea (shortness of breath)Respiratory, thoracic and mediastinal disorders2/30
Pulmonary/Upper Respiratory: HypoxiaRespiratory, thoracic and mediastinal disorders2/30
ThrombosisCardiac disorders2/30
Cardiac General: HypotensionCardiac disorders1/30
Constitutional Symptoms: FeverGeneral disorders1/30
CreatinineRenal and urinary disorders1/30
Gastrointestinal:Mucositis/stomatitis (clinical exam)::oral cavityGastrointestinal disorders1/30
Most frequent other events
Showing 10 of 544
Most frequent other events
EventArm 2-Recipients
Blood/Bone Marrow:HemoglobinBlood and lymphatic system disorders30/30
Coagulation: PTT (partial thromboplastin time)Blood and lymphatic system disorders28/30
Blood/Bone Marrow:Leukocytes (total WBC)Blood and lymphatic system disorders27/30
Metabolic/Laboratory: Glucose, serum-high (hyperglycemia)Metabolism and nutrition disorders27/30
Blood/Bone Marrow:PlateletsBlood and lymphatic system disorders26/30
Blood/Bone Marrow:Neutrophils/granulocytes (ANC/AGC)Blood and lymphatic system disorders26/30
Metabolic/Laboratory: Sodium, serum-low (hyponatremia)Metabolism and nutrition disorders25/30
Metabolic/Laboratory: AST, SGOT (serum glutamic oxaloacetic)Metabolism and nutrition disorders24/30
Metabolic/Laboratory: Calcium, serum-low (hypocalcemia)Metabolism and nutrition disorders24/30
Gastrointestinal:DiarrheaGastrointestinal disorders22/30

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Arm 1-Sibling DonorsArm 2-RecipientsTotal
<=18 years171431
Between 18 and 65 years131629
>=65 years000
Age, Continuous
Age, Continuous(years)Arm 1-Sibling DonorsArm 2-RecipientsTotal
Mean21.12 ± 10.919.98 ± 5.820.55 ± 8.35
Sex: Female, Male
Sex: Female, Male(Participants)Arm 1-Sibling DonorsArm 2-RecipientsTotal
Female191029
Male112031
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Arm 1-Sibling DonorsArm 2-RecipientsTotal
Hispanic or Latino112
Not Hispanic or Latino292958
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Arm 1-Sibling DonorsArm 2-RecipientsTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American000
White303060
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(Participants)Arm 1-Sibling DonorsArm 2-RecipientsTotal
United States303060
Number of Prior Regimens of Participants that Received Stem Cell Transplant
Number of Prior Regimens of Participants that Received Stem Cell Transplant(regimens)Arm 1-Sibling DonorsArm 2-RecipientsTotal
Patient # 1—55
Patient # 2—33
Patient # 3—22
Patient # 4—33
Patient # 6—22
Patient # 8—11
Patient # 9—22
Patient # 10—22
Patient # 12—22
Patient # 13—33
Patient # 14—11
Patient # 15—22
Patient # 17—22
Patient # 18—22
Patient # 20—33
Patient # 21—11
Patient # 22—11
Patient # 24—22
Patient # 25—22
Patient # 27—11
Patient # 28 (c)—11
Patient # 29—22
Patient # 30—11
Number of Prior Regimens of Participants that Did Not Receive Stem Cell Transplant
Number of Prior Regimens of Participants that Did Not Receive Stem Cell Transplant(regimens)Arm 1-Sibling DonorsArm 2-RecipientsTotal
Patient # 5—22
Patient # 7—11
Patient # 11—33
Patient # 16—22
Patient # 19—22
Patient # 23—44
Patient # 26—33

8 further baseline measures are reported on the registry.

08

Study locations

1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike
    Bethesda, Maryland 20892, United States
09

References and documents

Publications

  • Dunst J, Sauer R, Burgers JM, Hawliczek R, Kurten R, Winkelmann W, Salzer-Kuntschik M, Muschenich M, Jurgens H. Radiation therapy as local treatment in Ewing's sarcoma. Results of the Cooperative Ewing's Sarcoma Studies CESS 81 and CESS 86. Cancer. 1991 Jun 1;67(11):2818-25. doi: 10.1002/1097-0142(19910601)67:113.0.co;2-y. PubMed 2025847 ↗
  • Demeocq F, Oberlin O, Benz-Lemoine E, Boilletot A, Gentet JC, Zucker JM, Behar C, Poutard P, Olive D, Brunat-Mentigny M, et al. Initial chemotherapy including ifosfamide in the management of Ewing's sarcoma: preliminary results. A protocol of the French Pediatric Oncology Society (SFOP). Cancer Chemother Pharmacol. 1989;24 Suppl 1:S45-7. doi: 10.1007/BF00253240. PubMed 2667789 ↗
  • Burdach S, Jurgens H, Peters C, Nurnberger W, Mauz-Korholz C, Korholz D, Paulussen M, Pape H, Dilloo D, Koscielniak E, et al. Myeloablative radiochemotherapy and hematopoietic stem-cell rescue in poor-prognosis Ewing's sarcoma. J Clin Oncol. 1993 Aug;11(8):1482-8. doi: 10.1200/JCO.1993.11.8.1482. PubMed 8101562 ↗
  • Baird K, Fry TJ, Steinberg SM, Bishop MR, Fowler DH, Delbrook CP, Humphrey JL, Rager A, Richards K, Wayne AS, Mackall CL. Reduced-intensity allogeneic stem cell transplantation in children and young adults with ultrahigh-risk pediatric sarcomas. Biol Blood Marrow Transplant. 2012 May;18(5):698-707. doi: 10.1016/j.bbmt.2011.08.020. Epub 2011 Sep 5. PubMed 21896345 ↗

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 31, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00043979
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Terry Fry, M.D. (Principal Investigator, National Institutes of Health Clinical Center (CC)) — Principal investigator
First posted
Aug 16, 2002
Start date
Sep 19, 2002
Primary completion
May 1, 2009
Completion
Dec 14, 2011
Results posted
Sep 13, 2013
Last update
May 31, 2017

Study contacts

Terry Fry, M.D.
principal investigator · National Cancer Institute (NCI)

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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