Clinical trial NCT00101140: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Adult Acute Erythroid Leukemia
Adult Acute Monoblastic and Acute Monocytic Leukemia
Adult Acute Myeloid Leukemia
Keywords: adult erythroleukemia (M6a)
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute monocytic leukemia (M5b)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloid leukemia in remission
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myelomonocytic leukemia (M4)
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-01-10
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Mayo Clinic
name: Mark R. Litzow, MD
role: STUDY_CHAIR
affiliation: Rambam Health Care Campus
name: Jacob M. Rowe, MD
References: