Phase 2
N=68
Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia
Acute Myeloid Leukemia · Adult Acute Megakaryoblastic Leukemia · Adult Acute Monoblastic Leukemia · Adult Acute Monocytic Leukemia · Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11
Bottom Line
View on ClinicalTrials.gov: NCT01168219 ↗Enrolled (actual)
68
Serious AEs
33.3%
Results posted
Apr 2018
Primary outcome: Primary: Progression-free Survival — 41.2; 26.9 percentage of patients
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Allogeneic Hematopoietic Stem Cell Transplantation (Procedure); Anti-Thymocyte Globulin (Biological); Azacitidine (Drug); Busulfan (Drug); Fludarabine Phosphate (Drug); Laboratory Biomarker Analysis (Other); Methotrexate (Drug); Pharmacological Study (Other); Tacrolimus (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Nov 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival |
41.2; 26.9 | — |
| SECONDARY Overall Survival (OS) |
45.7; 31.2 | — |
| SECONDARY 100-day Mortality |
10 | — |
Summary
This phase II clinical trial is studying how well giving busulfan, fludarabine phosphate, and anti-thymocyte globulin followed by donor stem cell transplant and azacitidine works in treating patients with high-risk myelodysplastic syndrome and older patients with acute myeloid leukemia. Giving low doses of chemotherapy, such as busulfan and fludarabine phosphate, before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-vs-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving anti-thymocyte globulin before transplant and giving azacitidine, tacrolimus, and methotrexate after the transplant may stop this from happening.
Eligibility Criteria
Inclusion Criteria
- Meets one of the following sets of criteria:
- Myelodysplastic syndromes (MDS):
- Disease with high-risk features (found either at diagnosis or before initiation of cytotoxic therapy), defined as one of the following:
- International prognostic scoring system (IPSS) risk >= intermediate-2
- Refractory anemia with excess blasts by French-American-British (FAB) classification
- High-risk cytogenetics (either complex or -7)
- Less than 10% bone marrow blasts as determined by bone marrow biopsy within the past 4 weeks (reduction in marrow blast percentage may be achieved with chemotherapy or other therapy)
- Less than 75 years old
- Acute myeloid leukemia (AML):
- No FAB M3
- No acute leukemia following blast transformation of prior chronic myelogenous leukemia or other myeloproliferative disease
- Patients with preceding MDS or treatment-related AML are eligible
- Prior central nervous system (CNS) involvement is allowed provided the disease is in remission at transplantation
- Morphologic complete remission (leukemia-free state) is defined as meeting all of the following criteria:
- Bone marrow blasts 40% with no symptomatic pulmonary disease
- Left ventricle ejection fraction (LVEF) >= 30% by echocardiogram (ECHO) or multigated acquisition (MUGA)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No uncontrolled diabetes mellitus or active serious infections
- No known hypersensitivity to E. coli-derived products, azacitidine, or mannitol
- No human immunodeficiency virus (HIV) infection or active hepatitis B or C
- Prior azacitidine or decitabine allowed
- No patients who progressed from MDS to AML during treatment with azacitidine or decitabine
- At least 4 weeks since prior deoxyribonucleic acid (DNA)-hypomethylating chemotherapy, radiotherapy, and/or surgery
- No more than 2 courses of consolidation therapy before transplantation (for patients with AML)
- Any consolidation regimen that does not require transplantation can be used
- No more than 6 months from documentation of morphologic CR to transplantation
Data sourced from ClinicalTrials.gov (NCT01168219). 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.