Phase 2
N=47
Hematopoietic Cell Transplantation for Pediatric Patients With Hematologic Malignancies
Acute Leukaemia · Chronic Disease · Leukemia · Myelodysplasia · Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT00795132 ↗Enrolled (actual)
47
Serious AEs
0.0%
Results posted
Aug 2012
Primary outcome: Primary: Number of High Risk Pediatric Patients With Successful Sustained Donor Engraftments — 16; 18; 10 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Busulfan (Drug); Anti-Thymocyte Globulin (Drug); Fludarabine (Drug); Cyclosporine (Drug); Mycophenolate mofetil (Drug)
- Age
- Pediatric, Adult
- Sex
- All
- Sponsor
- University of Utah
- Primary completion
- Jul 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of High Risk Pediatric Patients With Successful Sustained Donor Engraftments |
16; 18; 10 | — |
| SECONDARY Two Year Overall Survival |
0.501; 0.395; 0.438 | — |
| SECONDARY Number of Participants Who Experienced Transplantation-related Mortality (TRM) |
0; 5; 1 | — |
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. 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.
Eligibility Criteria
Inclusion Criteria
- 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 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 50% with standard transplantation they may be eligible for inclusion, but such patients must be reviewed with the protocol chairman prior to enrollment.
Exclusion Criteria
- Patients must be in a CR ( 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.
Data sourced from ClinicalTrials.gov (NCT00795132). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.