Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia

NCT01168219 | Completed Phase 2 Results

• 6 other identifiers: NCI-2011-02053CDR0000681025CALGB-100801CALGB 100801U10CA180821U10CA031946
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 17

Brief Summary

This phase II clinical trial is studying how well giving busulfan, fludarabine phosphate, and anti-thymocyte globulin followed by donor stem cell transplant and azacitidine works in treating patients with high-risk myelodysplastic syndrome and older patients with acute myeloid leukemia. Giving low doses of chemotherapy, such as busulfan and fludarabine phosphate, before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-vs-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving anti-thymocyte globulin before transplant and giving azacitidine, tacrolimus, and methotrexate after the transplant may stop this from happening.

Conditions

Acute Myeloid Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p21.3;q23.3); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Progression-free survival rate (percentage) at 2 and 5 years is defined as the percentage of patients who are alive and progression free at 2 and 5 years from date of transplantation respectively. AML progression is defined as: * Reappearance of leukemia blast cells in peripheral blood and \> 5% blasts in marrow * If no circulating blasts, but the marrow contains 5-20% blasts, a repeat bone marrow \>= 1 week later with \> 5% blasts * Development of extramedullary leukemia MDS progression is defined as * For patients with \<5% bone marrow blasts: ≥50% increase in blasts to \>5% blasts * For patients with 5-10% bone marrow blasts: ≥50% increase to \>10% blasts * Any of the following: Reappearance of prior documented characteristic cytogenetic abnormality or refractory cytopenias with unequivocal evidence of dysplasia on bone marrow biopsy/aspirate

  Up to 5 years

Secondary Outcomes (2)

• Overall Survival (OS)

  Up to 5 years

• 100-day Mortality

  Up to 100 days post-treatment

Study Arms (1)

Treatment (chemotherapy and transplant)

EXPERIMENTAL

REDUCED-INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3, busulfan IV over 45 minutes on days -6 to -3, and anti-thymocyte globulin IV over 4-10 hours on days -6 to -5 (matched sibling donor \[MSD\]) or -6 to -4 (matched unrelated donor \[MUD\]). TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day 0 or on days 0-1. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus PO or IV on days -2 to 90 with taper on days 150-180. Patients also receive methotrexate IV on days 1, 3, 6 (MSD), and 11 (MUD). CONSOLIDATION: Beginning on day 42, patients receive azacitidine SC or IV on days 1.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Biological: Anti-Thymocyte Globulin; Drug: Azacitidine; Drug: Busulfan; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Methotrexate; Other: Pharmacological Study; Drug: Tacrolimus

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic hematopoietic stem cell transplantation

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Treatment (chemotherapy and transplant)

Anti-Thymocyte Globulin BIOLOGICAL

Given IV

Also known as: Antithymocyte Globulin, Antithymocyte Serum, ATG, ATS

Treatment (chemotherapy and transplant)

Azacitidine DRUG

Given SC or IV

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, Onureg, U-18496, Vidaza

Treatment (chemotherapy and transplant)

Busulfan DRUG

Given IV

Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508

Treatment (chemotherapy and transplant)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (chemotherapy and transplant)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (chemotherapy and transplant)

Methotrexate DRUG

Given IV

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039

Treatment (chemotherapy and transplant)

Pharmacological Study OTHER

Correlative studies

Treatment (chemotherapy and transplant)

Tacrolimus DRUG

Given PO or IV

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (chemotherapy and transplant)

Eligibility Criteria

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

You may qualify if:

• Meets one of the following sets of criteria:
• Myelodysplastic syndromes (MDS):
• Disease with high-risk features (found either at diagnosis or before initiation of cytotoxic therapy), defined as one of the following:
• International prognostic scoring system (IPSS) risk \>= intermediate-2
• Refractory anemia with excess blasts by French-American-British (FAB) classification
• High-risk cytogenetics (either complex or -7)
• Less than 10% bone marrow blasts as determined by bone marrow biopsy within the past 4 weeks (reduction in marrow blast percentage may be achieved with chemotherapy or other therapy)
• Less than 75 years old
• Acute myeloid leukemia (AML):
• No FAB M3
• No acute leukemia following blast transformation of prior chronic myelogenous leukemia or other myeloproliferative disease
• Patients with preceding MDS or treatment-related AML are eligible
• Prior central nervous system (CNS) involvement is allowed provided the disease is in remission at transplantation
• Morphologic complete remission (leukemia-free state) is defined as meeting all of the following criteria:
• Bone marrow blasts \< 5% (as determined by bone marrow within the past 4 weeks), but without requirement for normal peripheral blood counts

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (17)

Beebe Medical Center

Lewes, Delaware, 19958, United States

Location

Christiana Care Health System-Christiana Hospital

Newark, Delaware, 19718, United States

Location

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Christiana Care - Union Hospital

Elkton, Maryland, 21921, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Cooper Hospital University Medical Center

Camden, New Jersey, 08103, United States

Location

Northwell Health NCORP

Lake Success, New York, 11042, United States

Location

Northwell Health/Center for Advanced Medicine

Lake Success, New York, 11042, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Vij R, Le-Rademacher J, Laumann K, Hars V, Owzar K, Shore T, Vasu S, Cashen A, Isola L, Shea T, DeMagalhaes-Silverman M, Hurd D, Meehan K, Beardell F, Devine S. A Phase II Multicenter Study of the Addition of Azacitidine to Reduced-Intensity Conditioning Allogeneic Transplant for High-Risk Myelodysplasia (and Older Patients with Acute Myeloid Leukemia): Results of CALGB 100801 (Alliance). Biol Blood Marrow Transplant. 2019 Oct;25(10):1984-1992. doi: 10.1016/j.bbmt.2019.06.007. Epub 2019 Jun 15.

  PMID: 31212080 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts

Interventions

Stem Cell Transplantation; Antilymphocyte Serum; Azacitidine; Busulfan; fludarabine phosphate; Methotrexate; merphos; Tacrolimus

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Anemia, Refractory; Anemia

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Butylene Glycols; Glycols; Alcohols; 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; Macrolides; Lactones

Results Point of Contact

• Title: Ravi Vij, MD
• Organization: Washington University School of Medicine

rvij@im.wustl.edu

Study Officials

• Ravi Vij

  Alliance for Clinical Trials in Oncology

  PRINCIPAL INVESTIGATOR

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: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2010
• First Posted: July 23, 2010
• Study Start: July 15, 2010
• Primary Completion: November 14, 2015
• Study Completion: February 1, 2020
• Last Updated: August 4, 2022
• Results First Posted: April 3, 2018

Record last verified: 2022-08

Locations

US (17)