Ignite Creation Date:
2024-05-05 @ 11:27 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00043979
Status:
COMPLETED
Last Update Posted:
2017-05-31
First Post:
2002-08-15
Brief Title:
Stem Cell Transplantation in Patients With High-Risk and Recurrent Pediatric Sarcomas
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Pilot Study of AllogeneicSyngeneic Blood Stem Cell Transplantation in Patients With High-Risk and Recurrent Pediatric Sarcomas
Status:
COMPLETED
Status Verified Date:
2017-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 patients bone marrow and begin producing normal cells In patients with certain cancers such as leukemia and lymphoma the donors immune cells attack the patients 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 donors cells see the patients 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
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 donors cells see the patients 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
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 Ewings sarcoma is susceptible to immune mediated mechanisms of cytolysis in vitro Interestingly for Ewings 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 Ewings 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 microgkg 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
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 Ewings sarcoma is susceptible to immune mediated mechanisms of cytolysis in vitro Interestingly for Ewings 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 Ewings 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 microgkg 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-C-0259 | None | None | None |