Acute LeukaemiaPhase 2NCT00795132
Hematopoietic Cell Transplantation for Pediatric Patients With Hematologic Malignancies
A Phase 2 study testing Busulfan, Anti-Thymocyte Globulin and Fludarabine in people with Acute Leukaemia and Chronic Disease, run by University of Utah at 1 site in United States.
Trial summary
This is a phase II trial of reduced intensity conditioning with Bu/Flu/ATG in pediatric patients with hematologic malignancies at high risk for transplant related mortality with standard transplantation. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Acute Leukaemia, Chronic Disease, Leukemia
- What is being tested?
- Busulfan, Anti-Thymocyte Globulin and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2004to Jul 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients must be age 21 or younger and must have hematologic malignancies treatable with allogeneic hematopoietic transplantation (acute and chronic leukemias, myelodysplasia or lymphomas, see protocol for further details). Patients qualify for this approach in four ways: 1) presence of organ system dysfunction or severe systemic infections that significantly increase transplant related mortality with standard myeloablative transplant regimens, 2) history of previous myeloablative allogeneic or autologous transplantation, 3) currently in a third or higher CR receiving an unrelated stem cell transplant, or 4) a combination of toxicities that leads the investigator to feel that the child is at high risk (>50%) of TRM. Patients eligible for inclusion based on consideration number 4 above cannot be enrolled unless discussed with the study chair.
- Organ system dysfunction: at least one of the following organ system dysfunction criteria plus minimum organ function listed in exclusion criteria qualify a patient for treatment on this protocol
- Pulmonary: DLCO, FEV1 or TLC/FVC <60% predicted. Patients too young for PFTs with suspected pulmonary toxicity should be assessed by a consulting pulmonologist. If the pulmonologist judges the child to have moderate-severe pulmonary disease they qualify for inclusion.
- Renal: creatinine clearance <60ml/m/1.73m2
- Hepatic: transaminases >4x normal or total bilirubin >2.0
- Cardiac: all patients with suspected cardiac toxicity should undergo a cardiac echo. If the shortening fraction (SF) is <25% a measurement of ejection fraction must be obtained. Patients qualify for reduced intensity therapy if the SF is <25% and the EF <50%.
- Infections: Patients with responsive but unresolved invasive infections. These infections may be fungal, bacterial or other opportunistic infections. Viral infections do not meet this eligibility criteria.
- Other patient groups at high risk for transplant related mortality: Patients with a history of a prior allogeneic or autologous transplantation and patients who are in CR3 or greater and receiving an unrelated stem cell transplant are also eligible for this protocol. If the investigator feels that a patient has a combination of risk factors that could increase their risk of transplant related mortality to >50% with standard transplantation they may be eligible for inclusion, but such patients must be reviewed with the protocol chairman prior to enrollment.
Who cannot join
- Patients must be in a CR (<5% blasts on BM morphology, no active CNS disease, see protocol) with the following exceptions:
- AML may proceed with M2 marrow status (<20% blasts).
- Lymphoma: residual disease must be responsive and non-bulky (<5cm largest diameter).
- Myelodysplasia: Patients with RA, and RAEB are eligible, but RAEB-IT patients are only eligible if treated to <5% blasts (RA) with chemotherapy.
- CML-BP must be treated to CR/CP2 to be eligible.
- Females who are pregnant
Show all 16Show fewer
- Patients who are HIV positive or who have other progressive infections
- Organ dysfunction: patients are ineligible for the following levels of severe organ system dysfunction:
- Cardiac: Ejection fraction <30%
- Pulmonary: Receiving continuous supplementary oxygen or any of the following: DLCO <30%, FVC/TLC < 30% or FEV1 <30%
- Hepatic: patients will be excluded for hepatic synthetic dysfunction evidenced by any of the following: prolongation of the prothrombin time with an INR >2.0, total serum bilirubin >3, or transaminases >10x normal.
- Renal: patients with a creatinine clearance <30ml/m/1.73m2 or who require dialysis are not eligible
- Donor Eligibility Criteria:
- Related or unrelated donor who is a 6/6 HLA match at HLA-A, B, and DRB1 locus. 5/6 matches are acceptable with mismatches at class I alleles (A and B), but DRB1 mismatches are not allowed. Intermediate resolution typing of class I and high resolution typing of class II alleles is required. (HLA-C and HLA-DQ matching is encouraged, but not required with the ideal donor matching at 10/10 alleles.)
- Unrelated cord blood may be used if matched at HLA-A, B and DRB1 at either 4/6, 5/6, or 6/6 antigens. The minimum mononuclear cell dose required for eligibility is 3 x 107 mononuclear cells/kg recipient body weight (based on frozen cell dose). It is strongly suggested that a back up unit of umbilical cord blood be reserved, though not requested, in case of rejection.
- Donors must pass required institutional and NMDP health and infectious disease screening.
Trial locations and contacts
1 site in 1 country.
United States1 site
Primary Children's Medical Center
Salt Lake City, Utah, 84112
About this study
Official title: Reduced Intensity Conditioning Hematopoietic Cell Transplantation for Pediatric Patients With Hematologic Malignancies at High Risk for Transplant Related Mortality With Standard Transplantation
This is a phase II trial of reduced intensity conditioning with Bu/Flu/ATG in pediatric patients with hematologic malignancies at high risk for transplant related mortality with standard transplantation. Patients qualify based on organ system dysfunction, active but stable infection, history of previous transplant or late stage disease. We plan to enroll 45 patients through the Pediatric Blood and Marrow Transplant Consortium (PBMTC) and anticipate that the outcome of the trial will pave the way for phase II or III disease specific protocols addressing efficacy of the approach compared to standard transplant approaches in better risk patients.
Read the detailed description
Summary/Proposal: Reduced Intensity Hematopoietic Cell Transplantation for High-Risk Relapsed Pediatric Hematologic Malignancies and Patients Ineligible for Standard Transplantation We propose a phase II trial of reduced intensity conditioning with Bu/Flu/ATG in pediatric patients with hematologic malignancies at high risk for transplant related mortality with standard transplantation. Patients qualify based on organ system dysfunction, active but stable infection, history of previous transplant, or late stage disease. We plan to enroll 45 patients through the Pediatric Blood and Marrow transplant Consortium (PBMTC) and anticipate that the outcome of the trial will pave the way for phase II or III disease specific protocols addressing efficacy of the approach compared to standard transplant approaches in better risk patients.
Hypothesis High risk pediatric hematologic malignancy patients ineligible for standard myeloablative HCT undergoing reduced intensity conditioning (RIC) HCT can achieve a sustained engraftment rate > 90% with a 100day TRM < 30% using either bone marrow or PBSC from related or unrelated donors. High risk pediatric patients undergoing RIC-HCT using related or unrelated cord blood can achieve a sustained engraftment rate >80% and a 100d TRM <30%.
Rationale for Reduced Intensity Approaches in High Risk Patients There are a number patient-specific risk factors associated with increased transplant related mortality. They can be broadly placed into three categories: pretransplant organ system dysfunction, active infections at the time of transplant, and degree of pretransplant therapy (previous transplants, third or subsequent remission, etc.).
The primary objective of this study is to determine the likelihood of achieving sustained donor engraftment using reduced intensity conditioning (fludarabine/busulfan/ATG) followed by hematopoietic cell transplantation (HCT) with either cord blood, bone marrow or peripheral blood stem cells (PBMTC) in pediatric patients with hematopoietic malignancies who are at high risk of transplant related mortality (TRM) with myeloablative HCT. Patients qualify based on organ system dysfunction, active but stable infection, history of previous transplant or late stage disease. We plan to enroll 45 patients through the Pediatric Blood and Marrow Transplant Consortium (PBMTC) and anticipate that the outcome of the trial will pave the way for phase II or III disease specific protocols addressing efficacy of the approach compared to standard transplant approaches in better risk patients.
Study procedures Patients receive their conditioning regimen consisting of fludarabine, busulfan, and ATG and then receive their stem cell transplant. Patients receive immunosuppression consisting of cyclosporine and mycophenolate mofetil. Patients with persistent or progressive disease may receive donor lymphocyte infusion off protocol.
- Conditions
- Acute Leukaemia, Chronic Disease, Leukemia, Myelodysplasia, Lymphoma
- Being tested
- Busulfan, Anti-Thymocyte Globulin, Fludarabine, Cyclosporine, Mycophenolate mofetil
- Keywords
- cancer, Hematologic Malignancies, Hematopoietic Cell Transplantation
- Medical subject headings
- Chronic Disease, Leukemia, Anemia, Refractory, with Excess of Blasts, Lymphoma, Neoplasms, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BusulfanDrug
Also called Busulfex
This drug is a bifunctional alkylating agent. Busulfan is highly toxic to noncycling or slowly-cycling cells. Pharmacokinetic studies of the IV formulation in pediatrics have shown that using a dose of 0.8mg/kg IV q6 hours most patients will achieve AUC levels between 800 and 1300 uM/min, representing steady state levels between 600-900ug/ml. The manufacturer recommends higher doses, 1.1mg/kg for children less than 12kg. Because this is a reduced intensity study and infants on the study will be very heavily pretreated we will use the lower dose of 0.8mg/kg q6 hours for a total of 8 doses for all patients.
Anti-Thymocyte GlobulinDrug
Also called Thymoglobulin® [Anti-thymocyte Globulin, (Rabbit)]
Thymoglobulin will be administered at a dose of 2.5 mg/kg recipient body weight intravenously on each of 4 successive mornings (Days -4, -3,-2,-1) for patients receiving unrelated grafts and at a dose of 2.5mg/kg as a single dose on d-1 for patients receiving related marrow grafts. ATG is infused over a minimum of 4 hours, but is generally better tolerated over 6-8 hours. Suggested premedications are acetaminophen (10 mg/kg/dose), diphenhydramine (1 mg/kg/dose), and methylprednisolone. The methylprednisolone should be given at a dose of
1mg/kg 30 minutes prior to the ATG, with another 1mg /kg four hours into the infusion (total 2mg/kg/d). Patients are observed continuously for possible allergic reactions throughout the infusion.
FludarabineDrug
Also called Fludara
Administration and Dosage: Fludarabine will be administered at a dose of 30 mg/m2 in 100 ml of D5W intravenously over one hour on each of six consecutive days -10 through -5 for unrelated grafts or d-7 through d-2 for related grafts. Fludarabine is a fluorinated nucleotide analog of the antiviral agent vidarabine, 9-beta-D-arabinofuranosyladenine. Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. The half-life of 2-fluoro-ara-A is approximately 10 hours. The mean total plasma clearance is 8.9 L/hr/m2 and the mean volume of distribution is 98 L/m2. Approximately 23% is excreted unchanged. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis.
CyclosporineDrug
Cyclosporine is a potent immunosuppressive agent that in animals prolongs survival of allogeneic transplants involving skin, kidney, liver, heart, pancreas, bone marrow, small intestine, and lung. The effectiveness of cyclosporine results from specific and reversible inhibition of immunocompetent lymphocytes in the G 0 - and G
1 -phase of the cell cycle. Administration and Dosage: Cyclosporin start on day -3 initially at a dose of 2.5mg/kg IV q12 hours or 3mg/kg/dose (neoral equivalent) PO q12 hours targeting suggested troughs of 250 to 350 ng/ml. Continuous infusion cyclosporin may be allowed per institutional preference. 3x daily dosing may be used for younger children to achieve therapeutic levels. PBMTC Protocol #ONC0313 19 Continuous infusion cyclosporin may be allowed per institutional preference.
Also called MMF, CellCept
MMF is a potent, selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. Administration and Dosage: Initial dosage will be IV or PO with switch to PO when tolerated. Starting doses will be 15 mg/kg/day bid (total dose 30mg/kg/d, IV same as PO dose) beginning day 0 with the first dose given approximately 4-6 hours after the stem cell infusion. This dose will stop on day +30 for patients receiving matched sibling BM/PBSC and UCB grafts, but will continue until day +40 and then taper at approximately 11%/wk over 8 weeks until patients are off at day +96.
| Study group | Role | What they receive |
|---|---|---|
| Related BM PBSC | Active comparator | Bone Marrow Peripheral Blood Stem Cell (BM PBSC) from a donor related to the participant/recipient Receives: Drug: Busulfan; Drug: Anti-Thymocyte Globulin; Drug: Fludarabine; Drug: Cyclosporine; Drug: Mycophenolate mofetil |
| Unrelated BM PBSC | Active comparator | Bone Marrow Peripheral Blood Stem Cell (BM PBSC) from a donor unrelated to the participant/recipient Receives: Drug: Busulfan; Drug: Anti-Thymocyte Globulin; Drug: Fludarabine; Drug: Cyclosporine; Drug: Mycophenolate mofetil |
| Unrelated Blood Cord | Active comparator | Blood Cord donated from a donor unrelated to the participant/recipient Receives: Drug: Busulfan; Drug: Anti-Thymocyte Globulin; Drug: Fludarabine; Drug: Cyclosporine; Drug: Mycophenolate mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of High Risk Pediatric Patients With Successful Sustained Donor Engraftments
Assessed donor engraftment in very high risk pediatric patients.
Measured: 24 months
Secondary outcomes (2)
Two Year Overall Survival
The probability that a given patient will be alive two years after transplantation.
Measured: 24 months
Number of Participants Who Experienced Transplantation-related Mortality (TRM)
Cumulative incidence transplantation-related mortality (TRM)
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2008 (estimated)
- Study startApr 2004
- Primary completionJul 2009
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute LeukaemiaStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Pulsipher, MD, Principal investigator, Primary Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00795132
- Sponsor's protocol ID
- HCI12073
- Status last verified
- Jul 2013
- First submitted
- 19 Nov 2008
- Last updated
- 30 Jul 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Pulsipher MA, Boucher KM, Wall D, Frangoul H, Duval M, Goyal RK, Shaw PJ, Haight AE, Grimley M, Grupp SA, Kletzel M, Kadota R. Reduced-intensity allogeneic transplantation in pediatric patients ineligible for myeloablative therapy: results of the Pediatric Blood and Marrow Transplant Consortium Study ONC0313. Blood. 2009 Aug 13;114(7):1429-36. doi: 10.1182/blood-2009-01-196303. Epub 2009 Jun 15.
PubMed 19528536
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduced Intensity Conditioning Hematopoietic Cell Transplantation for Pediatric Patients With Hematologic Malignancies at High Risk for Transplant Related Mortality With Standard Transplantation
- ClinicalTrials.gov ID
- NCT00795132
- Acronym / sponsor ID
- HCI12073
- Conditions
- Acute Leukaemia, Chronic Disease, Leukemia, Myelodysplasia, Lymphoma
- Keywords
- cancer, Hematologic Malignancies, Hematopoietic Cell Transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- Apr 2004
- Primary completion
- Jul 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 21 Nov 2008 (estimated)
- Results
- Posted 20 Aug 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II trial of reduced intensity conditioning with Bu/Flu/ATG in pediatric patients with hematologic malignancies at high risk for transplant related mortality with standard transplantation. Patients qualify based on organ system dysfunction, active but stable infection, history of previous transplant or late stage disease. We plan to enroll 45 patients through the Pediatric Blood and Marrow Transplant Consortium (PBMTC) and anticipate that the outcome of the trial will pave the way for phase II or III disease specific protocols addressing efficacy of the approach compared to standard transplant approaches in better risk patients.
Detailed description
Summary/Proposal: Reduced Intensity Hematopoietic Cell Transplantation for High-Risk Relapsed Pediatric Hematologic Malignancies and Patients Ineligible for Standard Transplantation We propose a phase II trial of reduced intensity conditioning with Bu/Flu/ATG in pediatric patients with hematologic malignancies at high risk for transplant related mortality with standard transplantation. Patients qualify based on organ system dysfunction, active but stable infection, history of previous transplant, or late stage disease. We plan to enroll 45 patients through the Pediatric Blood and Marrow transplant Consortium (PBMTC) and anticipate that the outcome of the trial will pave the way for phase II or III disease specific protocols addressing efficacy of the approach compared to standard transplant approaches in better risk patients.
Hypothesis High risk pediatric hematologic malignancy patients ineligible for standard myeloablative HCT undergoing reduced intensity conditioning (RIC) HCT can achieve a sustained engraftment rate > 90% with a 100day TRM < 30% using either bone marrow or PBSC from related or unrelated donors. High risk pediatric patients undergoing RIC-HCT using related or unrelated cord blood can achieve a sustained engraftment rate >80% and a 100d TRM <30%.
Rationale for Reduced Intensity Approaches in High Risk Patients There are a number patient-specific risk factors associated with increased transplant related mortality. They can be broadly placed into three categories: pretransplant organ system dysfunction, active infections at the time of transplant, and degree of pretransplant therapy (previous transplants, third or subsequent remission, etc.).
The primary objective of this study is to determine the likelihood of achieving sustained donor engraftment using reduced intensity conditioning (fludarabine/busulfan/ATG) followed by hematopoietic cell transplantation (HCT) with either cord blood, bone marrow or peripheral blood stem cells (PBMTC) in pediatric patients with hematopoietic malignancies who are at high risk of transplant related mortality (TRM) with myeloablative HCT. Patients qualify based on organ system dysfunction, active but stable infection, history of previous transplant or late stage disease. We plan to enroll 45 patients through the Pediatric Blood and Marrow Transplant Consortium (PBMTC) and anticipate that the outcome of the trial will pave the way for phase II or III disease specific protocols addressing efficacy of the approach compared to standard transplant approaches in better risk patients.
Study procedures Patients receive their conditioning regimen consisting of fludarabine, busulfan, and ATG and then receive their stem cell transplant. Patients receive immunosuppression consisting of cyclosporine and mycophenolate mofetil. Patients with persistent or progressive disease may receive donor lymphocyte infusion off protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Related BM PBSC | Active comparator | Drug: Busulfan, Drug: Anti-Thymocyte Globulin, Drug: Fludarabine, Drug: Cyclosporine, Drug: Mycophenolate mofetilBone Marrow Peripheral Blood Stem Cell (BM PBSC) from a donor related to the participant/recipient |
| Unrelated BM PBSC | Active comparator | Drug: Busulfan, Drug: Anti-Thymocyte Globulin, Drug: Fludarabine, Drug: Cyclosporine, Drug: Mycophenolate mofetilBone Marrow Peripheral Blood Stem Cell (BM PBSC) from a donor unrelated to the participant/recipient |
| Unrelated Blood Cord | Active comparator | Drug: Busulfan, Drug: Anti-Thymocyte Globulin, Drug: Fludarabine, Drug: Cyclosporine, Drug: Mycophenolate mofetilBlood Cord donated from a donor unrelated to the participant/recipient |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Patients must be age 21 or younger and must have hematologic malignancies treatable with allogeneic hematopoietic transplantation (acute and chronic leukemias, myelodysplasia or lymphomas, see protocol for further details). Patients qualify for this approach in four ways: 1) presence of organ system dysfunction or severe systemic infections that significantly increase transplant related mortality with standard myeloablative transplant regimens, 2) history of previous myeloablative allogeneic or autologous transplantation, 3) currently in a third or higher CR receiving an unrelated stem cell transplant, or 4) a combination of toxicities that leads the investigator to feel that the child is at high risk (>50%) of TRM. Patients eligible for inclusion based on consideration number 4 above cannot be enrolled unless discussed with the study chair.
- Organ system dysfunction: at least one of the following organ system dysfunction criteria plus minimum organ function listed in exclusion criteria qualify a patient for treatment on this protocol
- Infections: Patients with responsive but unresolved invasive infections. These infections may be fungal, bacterial or other opportunistic infections. Viral infections do not meet this eligibility criteria.
- Other patient groups at high risk for transplant related mortality: Patients with a history of a prior allogeneic or autologous transplantation and patients who are in CR3 or greater and receiving an unrelated stem cell transplant are also eligible for this protocol. If the investigator feels that a patient has a combination of risk factors that could increase their risk of transplant related mortality to >50% with standard transplantation they may be eligible for inclusion, but such patients must be reviewed with the protocol chairman prior to enrollment.
Key exclusion criteria (16 listed)
- Patients must be in a CR (<5% blasts on BM morphology, no active CNS disease, see protocol) with the following exceptions:
- Females who are pregnant
- Patients who are HIV positive or who have other progressive infections
- Organ dysfunction: patients are ineligible for the following levels of severe organ system dysfunction:
- Related or unrelated donor who is a 6/6 HLA match at HLA-A, B, and DRB1 locus. 5/6 matches are acceptable with mismatches at class I alleles (A and B), but DRB1 mismatches are not allowed. Intermediate resolution typing of class I and high resolution typing of class II alleles is required. (HLA-C and HLA-DQ matching is encouraged, but not required with the ideal donor matching at 10/10 alleles.)
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 |
|---|---|---|
| BusulfanAlso: BusulfexThis drug is a bifunctional alkylating agent. Busulfan is highly toxic to noncycling or slowly-cycling cells. Pharmacokinetic studies of the IV formulation in pediatrics have shown that using a dose of 0.8mg/kg IV q6 hours most patients will achieve AUC levels between 800 and 1300 uM/min, representing steady state levels between 600-900ug/ml. The manufacturer recommends higher doses, 1.1mg/kg for children less than 12kg. Because this is a reduced intensity study and infants on the study will be very heavily pretreated we will use the lower dose of 0.8mg/kg q6 hours for a total of 8 doses for all patients. | Drug | Related BM PBSC, Unrelated BM PBSC, Unrelated Blood Cord |
| Anti-Thymocyte GlobulinAlso: Thymoglobulin® [Anti-thymocyte Globulin, (Rabbit)]Thymoglobulin will be administered at a dose of 2.5 mg/kg recipient body weight intravenously on each of 4 successive mornings (Days -4, -3,-2,-1) for patients receiving unrelated grafts and at a dose of 2.5mg/kg as a single dose on d-1 for patients receiving related marrow grafts. ATG is infused over a minimum of 4 hours, but is generally better tolerated over 6-8 hours. Suggested premedications are acetaminophen (10 mg/kg/dose), diphenhydramine (1 mg/kg/dose), and methylprednisolone. The methylprednisolone should be given at a dose of 1mg/kg 30 minutes prior to the ATG, with another 1mg /kg four hours into the infusion (total 2mg/kg/d). Patients are observed continuously for possible allergic reactions throughout the infusion. | Drug | Related BM PBSC, Unrelated BM PBSC, Unrelated Blood Cord |
| FludarabineAlso: FludaraAdministration and Dosage: Fludarabine will be administered at a dose of 30 mg/m2 in 100 ml of D5W intravenously over one hour on each of six consecutive days -10 through -5 for unrelated grafts or d-7 through d-2 for related grafts. Fludarabine is a fluorinated nucleotide analog of the antiviral agent vidarabine, 9-beta-D-arabinofuranosyladenine. Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. The half-life of 2-fluoro-ara-A is approximately 10 hours. The mean total plasma clearance is 8.9 L/hr/m2 and the mean volume of distribution is 98 L/m2. Approximately 23% is excreted unchanged. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis. | Drug | Related BM PBSC, Unrelated BM PBSC, Unrelated Blood Cord |
| CyclosporineCyclosporine is a potent immunosuppressive agent that in animals prolongs survival of allogeneic transplants involving skin, kidney, liver, heart, pancreas, bone marrow, small intestine, and lung. The effectiveness of cyclosporine results from specific and reversible inhibition of immunocompetent lymphocytes in the G 0 - and G 1 -phase of the cell cycle. Administration and Dosage: Cyclosporin start on day -3 initially at a dose of 2.5mg/kg IV q12 hours or 3mg/kg/dose (neoral equivalent) PO q12 hours targeting suggested troughs of 250 to 350 ng/ml. Continuous infusion cyclosporin may be allowed per institutional preference. 3x daily dosing may be used for younger children to achieve therapeutic levels. PBMTC Protocol #ONC0313 19 Continuous infusion cyclosporin may be allowed per institutional preference. | Drug | Related BM PBSC, Unrelated BM PBSC, Unrelated Blood Cord |
| Mycophenolate mofetilAlso: MMF, CellCeptMMF is a potent, selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. Administration and Dosage: Initial dosage will be IV or PO with switch to PO when tolerated. Starting doses will be 15 mg/kg/day bid (total dose 30mg/kg/d, IV same as PO dose) beginning day 0 with the first dose given approximately 4-6 hours after the stem cell infusion. This dose will stop on day +30 for patients receiving matched sibling BM/PBSC and UCB grafts, but will continue until day +40 and then taper at approximately 11%/wk over 8 weeks until patients are off at day +96. | Drug | Related BM PBSC, Unrelated BM PBSC, Unrelated Blood Cord |
Primary outcome
Number of High Risk Pediatric Patients With Successful Sustained Donor Engraftments
Time frame: 24 months
Assessed donor engraftment in very high risk pediatric patients.
2 secondary outcomes
Two Year Overall Survival
Time frame: 24 months
Number of Participants Who Experienced Transplantation-related Mortality (TRM)
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 19528536Pulsipher MA, Boucher KM, Wall D, Frangoul H, Duval M, Goyal RK, Shaw PJ, Haight AE, Grimley M, Grupp SA, Kletzel M, Kadota R. Reduced-intensity allogeneic transplantation in pediatric patients ineligible for myeloablative therapy: results of the Pediatric Blood and Marrow Transplant Consortium Study ONC0313. Blood. 2009 Aug 13;114(7):1429-36. doi: 10.1182/blood-2009-01-196303. Epub 2009 Jun 15.
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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.
Michael Pulsipher, MD principal investigator
Primary Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Busulfan, Anti-Thymocyte Globulin and Fludarabine in people with Acute Leukaemia and Chronic Disease, run by University of Utah 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 8 inclusion and 16 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 30 Jul 2013. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of High Risk Pediatric Patients With Successful Sustained Donor Engraftments (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00795132, which also lists 1 linked publication.
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 30 Jul 2013.