Fludarabine and Busulfan Followed by Allogeneic Stem Cell Transplant in Treating Older Patients With Acute Myeloid Leukemia in First Complete Remission

Adult Acute Myeloid Leukemia in Remission Clinical Trial

Official title:

A Phase II Study Of Allogeneic Transplant For Older Patients With AML In First Morphologic Complete Remission Using A Non-Myeloablative Preparative Regimen

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00070135
• Other study ID #: CALGB-100103
• Secondary ID: CDR0000330001NCI
• Status: Completed
• Phase: Phase 2
• Start date: January 2004
• Est. completion date: June 15, 2016

Study information

• Verified date: May 2018
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well fludarabine and busulfan followed by a donor (allogeneic) stem cell transplant work in treating older patients with acute myeloid leukemia that is in first complete remission. Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stops 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. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving tacrolimus, methotrexate, and rabbit antithymocyte globulin before or after the transplant may stop this from happening.

Description:

PRIMARY OBJECTIVES:

I. Determine if allogeneic transplantation from a matched sibling or unrelated donor using a non-myeloablative preparative regimen results in a 2-year disease-free survival (DFS) that is better than historical results using standard chemotherapy.

SECONDARY OBJECTIVES:

I. Determine 2-year actuarial risks of transplant-related mortality, acute and chronic graft-versus-host (GVHD) disease and relapse among patients with acute myeloid leukemia (AML) in first complete remission (CR1) following a non-myeloablative preparative regimen.

II. To examine recovery of T and B cell number and function following non-myeloablative stem cell transplant.

III. To examine the time course of T, B and myeloid progenitor chimerism following this preparative regimen.

IV. To characterize the pharmacokinetics of intravenous busulfan used in a non-myeloablative preparation regimen in AML patients age >= 60 years.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive fludarabine intravenously (IV) over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive tacrolimus orally (PO) or IV twice daily (BID) on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2.

ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRASNPLANTATION (PBSC): Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim subcutaneously (SC) daily beginning on day 12 and continuing until blood counts recover.

Patients are followed monthly for 1 year, every 3 months for 1 year, and then every 6 months for 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: June 15, 2016
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 74 Years

Eligibility

Eligibility Criteria:

• Patients with acute myeloid leukemia (AML) (excluding French-American-British [FAB] classification system M3) who have achieved a first morphologic complete remission and who meet the criteria below; patients with preceding myelodysplastic syndrome (MDS) or treatment-related AML are eligible; patients with prior central nervous system (CNS) involvement are eligible as long as disease is in remission at transplant; patients with acute leukemia following blast transformation of prior chronic myeloid leukemia (CML) or other myeloproliferative disease are excluded

• Complete remission (CR) will be defined according to the revised recommendations of the International Working Group (24) as all of the following:

• Normal bone marrow morphology with < 5% blasts

• Absolute neutrophil count (ANC) > 1,000/uL, referring to the count needed to confirm that the patient achieved a CR

• Platelet count > 100,000/uL

• No extramedullary leukemia

• No blasts in peripheral blood

• CR was achieved after one or two (but no more than two) cycles of induction chemotherapy with standard cytotoxic chemotherapy (e.g., cytarabine and an anthracycline) or after no more than four cycles of a hypomethylating agent containing regimen including either 5-azacytidine or decitabine

• Patients may have received as many as but no more than two cycles of consolidation therapy prior to transplant; any consolidation regimen that does not require transplant can be used; no more than 6 months can elapse from documentation of morphologic CR to transplant; the platelet count does not need to be > 100,000/uL after consolidation, as long as the bone marrow assessment prior to transplant does not show relapse

• Identification of hematopoietic cell donor

• >= 4 weeks since prior chemotherapy, radiation therapy, and surgery

• Performance status 0-2

• Diffusion capacity of carbon monoxide (DLCO) > 40% with no symptomatic pulmonary disease

• Left ventricular ejection fraction (LVEF) by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) >= 30%

• No uncontrolled diabetes mellitus or active serious infection requiring antibiotics

• No known hypersensitivity to E. coli-derived products

• No human immunodeficiency virus (HIV) infection

• Calculated creatinine clearance >= 40 cc/min

• Bilirubin < 2 mg/dL

• If bilirubin is 2-3 mg/dL, but direct bilirubin is normal then patient will be considered eligible

• Aspartate aminotransferase (AST) < 3 x upper limit of normal

• DONOR: HLA-identical sibling (6/6); the donor must be determined to be an human leukocyte antigen (HLA)-identical sibling (6/6) by serologic typing for class (A, B) and low resolution molecular typing for class II (DRB1)

• DONOR: Matched unrelated donor (10/10); high resolution molecular typing at the following loci is required: HLA-A, -B, -C, -DRB1, and -DQB1

• DONOR: the donor must be healthy and must be an acceptable donor as per institutional standards for stem cell donation

• DONOR: the donor must have no significant cardiopulmonary, renal, endocrine, or hepatic disease

• DONOR: there is no donor age restriction if the donor is a matched sibling

• DONOR: syngeneic donors are not eligible

Related Conditions & MeSH terms

• Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
• Adult Acute Myeloid Leukemia in Remission
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Biological:
• filgrastim
Given SC
• Anti-Thymocyte Globulin
Given IV

Drug:
• busulfan
Given IV
• fludarabine phosphate
Given IV
• methotrexate
Given IV
• tacrolimus
Given PO or IV

Procedure:
• Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic PBSC transplantation

Locations

Country	Name	City	State
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber/Brigham and Women's Cancer Center	Boston	Massachusetts
United States	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Monter Cancer Center of the North Shore-LIJ Health System	Lake Success	New York
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	Don Monti Comprehensive Cancer Center at North Shore University Hospital	Manhasset	New York
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Mount Sinai Medical Center	New York	New York
United States	New York Weill Cornell Cancer Center at Cornell University	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	2 Year Disease Free Survival In Unrelated Donor Recipient Group	Percentage of participants who were alive and relapse free at 2 years for patients who were matched with an unrelated donor for transplant. The 2 year disease free survival, with 95% confidence interval, was estimated using the Kaplan Meier method.; A relapse is defined as any of the following: Reappearance of leukemia blasts cells in peripheral blood; >5% blasts in the marrow, not attributable to another cause (e.g., bone marrow regeneration); If there are no circulating blasts, but the marrow contains 5-20% blasts, a repeat bone marrow = 1 week later with >5% blasts is necessary to meet the criteria for relapse; The development of extramedullary leukemia or leukemic cells in the cerebral spinal fluid	2 years
Secondary	2 Year DFS for All Patients	Percentage of participants who were alive and relapse free at 2 years for all patients. The 2 year disease free survival, with 95% confidence interval, was estimated using the Kaplan Meier method.	Up to 2 years
Secondary	Non-relapse Mortality (NRM)	Percentage of patients who died due to causes other than relapse	Up to 5 years