Donor Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia in Remission

NCT ID: NCT00101140

Last Updated: 2017-10-19

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL

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.

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)

Study Design

• Primary Study Purpose: TREATMENT

Interventions

anti-thymocyte globulin

Intervention Type: DRUG

fludarabine phosphate

Intervention Type: DRUG

thiotepa

Intervention Type: DRUG

biological therapy

Intervention Type: PROCEDURE

bone marrow ablation with stem cell support

Intervention Type: PROCEDURE

chemotherapy

Intervention Type: PROCEDURE

non-specific immune-modulator therapy

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role: lead

Principal Investigators

Mark R. Litzow, MD

Role: STUDY_CHAIR

Mayo Clinic

Jacob M. Rowe, MD

Role:

Rambam Health Care Campus

Other Identifiers

ECOG-E1903

Identifier Type: -

Identifier Source: secondary_id

CDR0000405838

Identifier Type: -

Identifier Source: org_study_id