Sarcoma
Conditions
Keywords
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
Brief summary
RATIONALE: Giving chemotherapy drugs, such as busulfan, melphalan, and thiotepa, before a donor stem cell transplant helps stop the growth of tumor cells and prepares the patient's bone marrow for the stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal tissues. Giving tacrolimus, sirolimus, and mycophenolate mofetil may stop this from happening. PURPOSE: This phase II trial is studying how well giving busulfan together with melphalan and thiotepa followed by a donor stem cell transplant works in treating patients with high-risk Ewing's tumors.
Detailed description
OBJECTIVES: * Evaluate disease-free and overall survival of patients with high-risk tumors of the Ewing's family treated with unmodified T-cell depleted allogeneic hematopoietic stem cell transplantation after cytoreduction comprising busulfan, melphalan, and thiotepa. * Determine the regimen-related morbidity and mortality in these patients. * Determine the incidence of acute and chronic graft-vs-host disease in patients treated with this regimen. * Determine the biologic response of minimal residual disease in patients treated with this regimen. OUTLINE: This is a prospective study. * Myeloablative preparative regimen: Patients receive busulfan IV over 2 hours every 6 hours on days -8 to -6, melphalan IV over 20 minutes on days -5 to -3, and thiotepa IV over 4 hours on day -2. * Allogeneic hematopoietic stem cell transplant: Patients undergo allogeneic bone marrow or T-cell depleted peripheral blood stem cell transplantation on day 0. * Graft-vs-host disease (GVHD) prophylaxis: Patients receive treatment according to institutional guidelines and are given treatment against infection. After completion of study treatment, patients are followed periodically for at least 3 years.
Interventions
PROCEDUREperipheral blood stem cell transplantation
DRUGbusulfan
DRUGmelphalan
DRUGthiotepa
PROCEDUREallogeneic bone marrow transplantation
PROCEDUREallogeneic hematopoietic stem cell transplantation
Sponsors
National Cancer Institute (NCI)
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 40 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of high-risk tumors of the Ewing's family as defined by 1 of the following: * Biopsy-proven disease with distant metastases to sites other than the lung * Relapsed disease after completion of prior standard front-line therapy or high-dose chemotherapy * Currently in complete remission (CR) with no evidence of disease (with or without minimal residual disease) or very good partial remission (i.e., CR with an abnormal bone scan) after prior standard or high-dose chemotherapy with local control * HLA-compatible stem cell donor available * Compatible donors include those matched at both HLA-A, -B, -C, -DR and 1 of 2 -DQ alleles by high-resolution molecular typing * Related or unrelated donor PATIENT CHARACTERISTICS: * Karnofsky performance status (PS) 70-100% (≥ 16 years old) OR Lansky PS 70-100% (\< 16 years old) * LVEF \> 50% at rest * SGOT \< 3 times upper limit of normal * Bilirubin \< 2.0 mg/dL (unless liver is involved with disease) * Creatinine normal AND/OR creatinine clearance \> 60 mL/min * Lung diffusion capacity \> 50% of predicted (corrected for hemoglobin) OR asymptomatic with a room air oxygen saturation of ≥ 98% * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No active uncontrolled viral, bacterial, or fungal infection * No HIV-1 or -2 positivity PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior therapy with 100 mg/m² of melphalan * No prior high-dose chemotherapy requiring autologous stem cell rescue * No prior radiotherapy to \> 50% of the pelvic marrow space
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Objective Response | 2 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients With HIGH RISK EWING'S SARCOMA FAMILY TUMOR MELPHALAN & THIOTEPA TREATMENT OF HIGH RISK EWING'S SARCOMA FAMILY TUMOR | 6 |
| Related Donors Any consenting healthy family donor who is HLA compatible with the recipient will be considered as a potential donor for transplant | 4 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Patients With HIGH RISK EWING'S SARCOMA FAMILY TUMOR | Related Donors | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 0 / 4 |
| serious Total, serious adverse events | 4 / 6 | 0 / 4 |
Outcome results
Primary
Overall Objective Response
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Patients With HIGH RISK EWING'S SARCOMA FAMILY TUMOR | Overall Objective Response | Very Good Partial Response (VGPR) | 4 participants |
| Patients With HIGH RISK EWING'S SARCOMA FAMILY TUMOR | Overall Objective Response | Complete Response (CR) | 1 participants |