Brief Title
Donor Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia in Remission
Official Title
Phase II Study of Haploidentical Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With High-Risk Acute Myeloid Leukemia in First Remission
Brief Summary
RATIONALE: A peripheral stem cell transplant may be able to replace blood-forming cells that
were destroyed by chemotherapy or radiation therapy. Sometimes the transplanted cells from a
donor can make an immune response against the body's normal cells. Giving total-body
irradiation together with fludarabine, thiotepa, and antithymocyte globulin before transplant
may stop this from happening.
PURPOSE: This phase II trial is studying how well a donor stem cell transplant works in
treating patients with acute myeloid leukemia in remission.
Detailed Description
OBJECTIVES:
Primary
- Determine the safety and antileukemia activity of haploidentical allogeneic peripheral
blood stem cell transplantation in patients with high-risk acute myeloid leukemia in
first remission.
Secondary
- Determine the early treatment-related mortality (before day 100) of patients treated
with this regimen.
- Determine the incidence of acute graft-versus-host disease in patients treated with this
regimen.
- Determine the incidence of graft failure in patients treated with this regimen.
- Correlate a mismatch in the expression of the natural killer cell inhibitory receptors
CD158a and CD158b with engraftment and disease recurrence in patients treated with this
regimen.
OUTLINE: This is a multicenter study.
Patients receive a preparative regimen comprising total-body irradiation twice on day -8;
fludarabine IV over 30 minutes on days -7 to -3; thiotepa IV over 2 hours twice on day -7;
and antithymocyte globulin IV over 4-6 hours on days -5 to -2. Patients undergo
haploidentical allogeneic peripheral blood stem cell transplantation on day 0.
Patients are followed at day 100, at least monthly for 2 years, and then periodically for 3
years.
PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study within 2.2 years.
Study Phase
Phase 2
Study Type
Interventional
Condition
Adult Acute Erythroid Leukemia
Intervention
anti-thymocyte globulin
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
0
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Morphologically confirmed acute myeloid leukemia of 1 of the following subtypes:
- Acute myeloblastic leukemia (M0, M1, M2)
- Acute myelomonocytic leukemia (M4)
- Acute monocytic leukemia (M5)
- Acute erythroleukemia (M6)
- Acute megakaryocytic leukemia (M7)
- Must have 1 of the following karyotypic abnormalities at the time of diagnosis:
- Complex cytogenetic abnormalities (≥ 3 cytogenetic clones)
- Abnormalities of chromosome 5 [-5 or del(5q)]
- Abnormalities of the long (q) arm of chromosome 3, 9, 11, 20, or 21
- Abnormalities of the short (p) arm of chromosome 17, monosomy 7, t(9;22), or t(6;9)
(8)
- In morphologic first complete remission*, as evidenced by all of the following for ≥ 4
weeks before study entry:
- Absolute neutrophil count > 1,000/mm^3
- Platelet count > 100,000/mm^3
- Leukemic blasts not present in the peripheral blood
- Cellularity of bone marrow biopsy > 20% with maturation of all cell lines
- Less than 5% blasts by bone marrow biopsy
- No extramedullary leukemia, such as CNS or soft tissue involvement NOTE: *Reduced
hemoglobin concentration or hematocrit has no bearing on remission status
- Haploidentical (3/6 or 4/6 antigen matched [A, B, and DR]) family donor available
PATIENT CHARACTERISTICS:
Age
- 18 to 59
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
Hepatic
- Bilirubin ≤ 2.0 mg/dL
- AST < 2 times upper limit of normal
Renal
- Creatinine ≤ 1.5 mg/dL
Cardiovascular
- Ejection fraction > 40% by MUGA or echocardiogram
- None of the following within the past 3 months:
- Myocardial infarction
- Significant congestive heart failure
- Significant cardiac arrhythmia
Pulmonary
- FEV_1 and DLCO > 50% of predicted
Immunologic
- HIV negative
- No active or unresolved infection
- No evidence of invasive fungal infection (e.g., positive blood or deep tissue cultures
or stains)
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No organ damage
- No other medical problem that would preclude study participation
- No other currently active tumor that would likely interfere with study treatment or
that would likely compromise the patient's morbidity or mortality
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent routine use of filgrastim (G-CSF) or sargramostim (GM-CSF) to accelerate
hematopoietic recovery post-transplantation
Chemotherapy
- More than 4 weeks since prior chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- More than 4 weeks since prior radiotherapy
Surgery
- Not specified
Gender
All
Ages
18 Years - 59 Years
Accepts Healthy Volunteers
No
Contacts
Mark R. Litzow, MD, ,
Administrative Informations
NCT ID
NCT00101140
Organization ID
CDR0000405838
Secondary IDs
ECOG-E1903
Study Sponsor
Eastern Cooperative Oncology Group
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Mark R. Litzow, MD, Study Chair, Mayo Clinic
Verification Date
October 2017