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

NCT00070135 | Completed Phase 2 Results DMC

• 4 other identifiers: CALGB-100103CDR0000330001NCI-2009-00438U10CA180821
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 21

Brief 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.

Conditions

Adult Acute Myeloid Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome

Keywords

adult acute myeloid leukemia in remission; secondary acute myeloid leukemia; adult acute monocytic leukemia (M5b); adult acute erythroid leukemia (M6); adult acute megakaryoblastic leukemia (M7); adult acute minimally differentiated myeloid leukemia (M0); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myelomonocytic leukemia (M4); adult acute monoblastic leukemia (M5a); adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with 11q23 (MLL) abnormalities

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 2 Year DFS for All Patients

  Up to 2 years

• Non-relapse Mortality (NRM)

  Up to 5 years

Study Arms (1)

Treatment (fludarabine, busulfan, allogeneic PBSC)

EXPERIMENTAL

PREPARATIVE REGIMEN: Patients receive fludarabine 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. GVHD PROPHYLAXIS: Patients receive tacrolimus PO or IV 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 PBSC: Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim SC daily beginning on day 12 and continuing until blood counts recover.

Biological: filgrastim; Biological: Anti-Thymocyte Globulin; Drug: busulfan; Drug: fludarabine phosphate; Drug: methotrexate; Drug: tacrolimus; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

Interventions

filgrastim BIOLOGICAL

Given SC

Treatment (fludarabine, busulfan, allogeneic PBSC)

Anti-Thymocyte Globulin BIOLOGICAL

Given IV

Treatment (fludarabine, busulfan, allogeneic PBSC)

busulfan DRUG

Given IV

Treatment (fludarabine, busulfan, allogeneic PBSC)

fludarabine phosphate DRUG

Given IV

Treatment (fludarabine, busulfan, allogeneic PBSC)

methotrexate DRUG

Given IV

Treatment (fludarabine, busulfan, allogeneic PBSC)

tacrolimus DRUG

Given PO or IV

Treatment (fludarabine, busulfan, allogeneic PBSC)

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSC transplantation

Also known as: HSC, HSCT

Treatment (fludarabine, busulfan, allogeneic PBSC)

Eligibility Criteria

• Age: 60 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (21)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, 19958, United States

Location

CCOP - Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Union Hospital of Cecil County

Elkton, Maryland, 21921, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber/Brigham and Women's Cancer Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, 08043, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Monter Cancer Center of the North Shore-LIJ Health System

Lake Success, New York, 11042, United States

Location

CCOP - North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Don Monti Comprehensive Cancer Center at North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

New York Weill Cornell Cancer Center at Cornell University

New York, New York, 10021, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210-1240, United States

Location

Related Publications (1)

• Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II Study of Allogeneic Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission Using a Reduced-Intensity Conditioning Regimen: Results From Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. doi: 10.1200/JCO.2015.62.7273. Epub 2015 Nov 2.

  PMID: 26527780 DERIVED

MeSH Terms

Conditions

Leukemia, Monocytic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Congenital Abnormalities

Interventions

Filgrastim; Antilymphocyte Serum; Busulfan; fludarabine phosphate; Methotrexate; Tacrolimus

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones

Results Point of Contact

• Title: Steven Devine, MD
• Organization: The Ohio State University

steven.devine@osumc.edu

Study Officials

• Steven M. Devine, MD

  Ohio State University Comprehensive Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2003
• First Posted: October 7, 2003
• Study Start: January 1, 2004
• Primary Completion: December 1, 2013
• Study Completion: June 15, 2016
• Last Updated: June 12, 2018
• Results First Posted: April 28, 2017

Record last verified: 2018-05

Locations

US (21)