Phase 3
N=25
Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome · Acute Myeloid Leukemia/Transient Myeloproliferative Disorder · Adult Acute Myeloid Leukemia in Remission · Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities · Adult Acute Myeloid Leukemia With Del(5q)
Bottom Line
View on ClinicalTrials.gov: NCT00322101 ↗Enrolled (actual)
25
Serious AEs
30.4%
Results posted
Oct 2013
Primary outcome: Primary: Overall Survival — 6; 6 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- total-body irradiation (Radiation); allogeneic hematopoietic stem cell transplantation (Procedure); cyclophosphamide (Drug); mycophenolate mofetil (Drug); busulfan (Drug); cyclosporine (Drug); fludarabine phosphate (Drug); peripheral blood stem cell transplantation (Procedure); nonmyeloablative allogeneic hematopoietic stem cell transplantation (Procedure); laboratory biomarker analysis (Other); cytogenetic analysis (Genetic); flow cytometry (Other); fluorescence in situ hybridization (Genetic); pharmacological study (Other); polymorphism analysis (Genetic); tacrolimus (Drug); methotrexate (Drug)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Fred Hutchinson Cancer Center
- Primary completion
- Apr 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival |
6; 6 | — |
| SECONDARY Progression-free Survival |
7; 5 | — |
| SECONDARY Non-relapse Mortality |
0; 0 | — |
| SECONDARY Donor Cell Engraftment |
11; 11 | — |
| SECONDARY Incidence of Disease Progression/Relapse |
7; 2 | — |
| SECONDARY Incidence and Severity of Acute and Chronic Graft-vs-host Disease |
1; 4 | — |
Summary
RATIONALE: Giving chemotherapy, such as fludarabine phosphate, busulfan, and cyclophosphamide, and total-body radiation therapy before a donor peripheral stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's 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. It is not yet known whether low-dose chemotherapy and total-body radiation therapy is more effective than high-dose chemotherapy in treating patients with myelodysplastic syndrome or acute myeloid leukemia.
PURPOSE: This phase III trial is studying low-dose conditioning to see how well it works compared to high-dose conditioning followed by peripheral blood stem cell transplant in treating patients with myelodysplastic syndromes or acute myeloid leukemia
Eligibility Criteria
Inclusion Criteria
- Myelodysplastic syndrome (MDS) or transformed acute myelogenous leukemia (transformed from MDS)
- De novo acute myelogenous leukemia (AML) beyond first remission
- Intermediate or high risk de novo AML in first complete response (at FHCRC unrelated donor recipients only)
- Chemotherapy required prior to HCT for all patients:
- A) Interval between start of a cycle of cytoreductive chemotherapy and infusion of donor stem cells must be at least 30 days; chemotherapy received for disease maintenance will be allowed during this time period
- B) All patients must have 12 years, nonsyngeneic) or unrelated donor, HLA phenotypically or genotypically identical at the allele level at A,B,C,DRQ1, and CBQ1
- DONOR: Related or unrelated donors who are genotypically or phenotypically matched by high resolution HLA typing (HLA-A, B, C, DRB1, and DQB1); class 1 single allele mismatch allowed
- DONOR: Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0201, and this type of mismatch is not allowed
- DONOR: A positive anti-donor cytotoxic crossmatch or flow cytometric assay is an absolute donor exclusion at FHCRC/SCCA
- DONOR: Age >= 12 years
- DONOR: Donors must consent to PBSC mobilization with G-CSF and leukaphereses; bone marrow as a source of stem cells will not be allowed
- DONOR: Donor must have adequate veins for leukaphereses or agree to placement of central venous catheter (femoral, subclavian)
Exclusion Criteria
- HIV seropositivity
- Fungal infections with radiographic progression after appropriate therapy for greater than one month
- Organ dysfunction
- Symptomatic coronary artery disease or ejection fraction 3 mg/dL, and symptomatic biliary disease will be excluded
- Karnofsky Performance Score < 70
- Lansky-Play Performance Score < 70 for pediatric patients
- Life expectancy severely limited (< 2 years) by disease other than MDS/AML
- Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment
- Patients with active non-hematological malignancies except:
- A) Patients with follicular or low grade lymphoma will be eligible as long as they have not and do not require active treatment for control of their disease
- B) Patients with localized non-melanoma skin malignancies
- Patients with poorly controlled hypertension who are unable to have blood pressure stabilized below 150/90 mm Hg on standard medication
- Females who are pregnant or breastfeeding
- Patients with systemic, uncontrolled infections
- Active CNS disease as identified by positive CSF cytospin
- DONOR: Identical twin
- DONOR: Age < 12 years
- DONOR: Pregnancy
- DONOR: HIV seropositivity
- DONOR: Inability to achieve adequate venous access
- DONOR: Known adverse reaction to G-CSF
Data sourced from ClinicalTrials.gov (NCT00322101). 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.