Busulfan, Fludarabine, Clofarabine With Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia

NCT00469014 | Completed Phase 2 Results DMC

• 1 other identifier: 2006-0200
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the best dose of clofarabine and fludarabine that can be given with busulfan followed by an allogeneic blood stem cell transplant. Researchers will study whether this combination can help to control the disease, and look at the safety of this combination. Researchers also want to find out if combining busulfan with clofarabine alone or combining busulfan with both fludarabine and clofarabine will improve the treatment, compared with the previous standard method using busulfan and fludarabine alone.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome; Chronic Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; AML; Myelodysplastic Syndrome; MDS; Chronic Myeloid Leukemia; CML; Busulfan; Busulfex; Myleran; Fludarabine; Fludara; Fludarabine Phosphate; Clofarabine; Clofarex; Clolar; Allogeneic stem cell transplantation; ASCT; Stem Cell; Gleevec; Imatinib Mesylate

Outcome Measures

Primary Outcomes (1)

• Treatment Related Mortality

  Number of participants with treatment related mortality (death) within the first 30 days following transplantation.

  First 30 Days

Study Arms (4)

Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine

ACTIVE COMPARATOR

4-day Treatment Period Day -6 to Day -2: Busulfan 30 mg/m\^2 intravenous (IV) Daily + Fludarabine 30 mg/m\^2 IV Daily; + Clofarabine 10 mg/m\^2 IV Daily; Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.

Drug: Clofarabine; Drug: Busulfan; Drug: Fludarabine; Other: Stem Cell Infusion; Drug: Thymoglobulin (ATG); Drug: Filgrastim

Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine

EXPERIMENTAL

4-day Treatment Period Day -6 to Day -2: Busulfan 20 mg/m\^2 IV + Fludarabine 20 mg/m\^2 IV Daily + Clofarabine 20 mg/m\^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.

Drug: Clofarabine; Drug: Busulfan; Drug: Fludarabine; Other: Stem Cell Infusion; Drug: Thymoglobulin (ATG); Drug: Filgrastim

Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine

EXPERIMENTAL

4-day Treatment Period Day -6 to Day -2: Busulfan 10 mg/m\^2 IV Daily + Fludarabine 10 mg/m\^2 IV Daily + Clofarabine 30 mg/m\^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.

Drug: Clofarabine; Drug: Busulfan; Drug: Fludarabine; Other: Stem Cell Infusion; Drug: Thymoglobulin (ATG); Drug: Filgrastim

Arm 4: Busulfan + Clofarabine

EXPERIMENTAL

4-day Treatment Period Day -6 to Day -2: Busulfan 40 mg/m\^2 IV Daily + Clofarabine 40 mg/m\^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.

Drug: Clofarabine; Drug: Busulfan; Other: Stem Cell Infusion; Drug: Thymoglobulin (ATG); Drug: Filgrastim

Interventions

Clofarabine DRUG

Day -6 to Day -3 for Arm 1 = 10 mg/m\^2 intravenous (IV) Daily; Arm 2 = 20 mg/m\^2 IV Daily; Arm 3 = 30 mg/m\^2 IV Daily; Arm 4 = 40 mg/m\^2 IV Daily

Also known as: Clofarex, Clolar

Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine; Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine; Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine; Arm 4: Busulfan + Clofarabine

Busulfan DRUG

Day -6 to Day -3 for Arm 1: 30 mg/m\^2 IV Daily; Arm 2: 20 mg/m\^2 IV Daily; Arm 3: 10 mg/m\^2 IV Daily; Arm 4: 40 mg/m\^2 IV Daily. Test dose Day -8 32 mg/ m\^2 IV over 45 min, rest on Day -7.

Also known as: Busulfex, Myleran

Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine; Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine; Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine; Arm 4: Busulfan + Clofarabine

Fludarabine DRUG

Day -6 to Day -3 for Arm 1: 30 mg/m\^2 IV Daily; Arm 2: 20 mg/m\^2 IV Daily; Arm 3: 10 mg/m\^2 IV Daily

Also known as: Fludarabine Phosphate, Fludara

Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine; Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine; Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine

Stem Cell Infusion OTHER

Day 0 stem cell infusion (Bone marrow or peripheral blood progenitor cells (PBPC))

Also known as: Bone Marrow Transplant, BMT, peripheral blood progenitor cells, PBPC, Unstimulated bone marrow transplant, bone marrow transplantation, ABM transplantations, autologous bone marrow transplantation

Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine; Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine; Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine; Arm 4: Busulfan + Clofarabine

Thymoglobulin (ATG) DRUG

Day -3 to Day -1 at 0.5 mg/kg IV on Day -3; 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1.

Also known as: Thymoglobulin, Antithymocyte Globulin

Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine; Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine; Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine; Arm 4: Busulfan + Clofarabine

Filgrastim DRUG

Subcutaneous injection daily, starting 1 week after Stem Cell Transplant.

Also known as: G-CSF, Granulocyte colony-stimulating factor, GCSF

Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine; Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine; Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine; Arm 4: Busulfan + Clofarabine

Eligibility Criteria

• Age: Up to 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis or 1) Acute myeloid leukemia past first remission, in first or subsequent relapse, or induction failures, 2) Myelodysplastic syndromes with intermediate or high risk International Prognostic Scoring System score (IPSS scores) (16), and having failed previous chemotherapy, or 3) Chronic Myeloid Leukemia, Philadelphia-chromosome positive and having failed / being resistant to therapy based on Gleevec or other tyrosine kinase inhibitors.
• Patient has not been administered intensive systemic chemotherapeutic drugs within 21 days prior to trial enrollment (bone marrow transplant (BMT) Day -9). Gleevec, alternative tyrosine kinase inhibitors, other nonmyelosuppressive agents, low dose cytarabine, hydroxyurea is permitted if indicated to control the leukemia. All tyrosine inhibitor- or other non-myelosuppressive agents have to be terminated at least one week prior to admission for this treatment.
• No uncontrolled infection. Protocol principal investigator (PI) will be final arbiter if there is uncertainty regarding whether a previous infection is resolved on appropriate antibiotics therapy.
• age \</= 60
• A related or unrelated donor who is HLA-matched or mismatched in 1 HLA, A, B, C, DR or DQ locus is acceptable (i.e. at least a 9/10 matched related or unrelated donor, matched with molecular high-resolution technique per current standard for the BMT program).
• ZUBROD performance status \<2
• Life expectancy is not severely limited by concomitant illness.
• Left ventricular ejection fraction \>/=45% No uncontrolled arrhythmias or symptomatic cardiac disease.
• Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLCO) \>/= 50% of expected corrected for hemoglobin. In patients \</= 7 years pulmonary function will be assessed per pediatric BMT routine
• Serum creatinine \</= 1.5 mg%.
• Serum glutamic pyruvic transaminase (SGPT) \</= 200 IU/ml, serum bilirubin and alkaline phosphatase within accepted laboratory standard normal limits or considered not clinically significant. No evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and perform liver biopsy pror to determining study eligibility.
• Female patient is not pregnant (negative human chorionic gonadotropin (hCG) pregnancy test in all women of child-bearing-potential in accordance with departmental routine).
• Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.

You may not qualify if:

• Effusion or ascites estimated to be \>1L prior to drainage.
• HIV-positive.
• Hepatitis C or HBsAg positive
• Prior stem cell transplant after a myeloablative conditioning program (such as busulfan-based using a total dose of \>/= 12 mg/kg given by mouth or \>/= 10 mg/kg IV, or a total-body irradiation-based program.
• Active or prior Central Nervous System (CNS) leukemia
• Biphenotypic acute leukemia.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Andersson BS, Valdez BC, de Lima M, Wang X, Thall PF, Worth LL, Popat U, Madden T, Hosing C, Alousi A, Rondon G, Kebriaei P, Shpall EJ, Jones RB, Champlin RE. Clofarabine +/- fludarabine with once daily i.v. busulfan as pretransplant conditioning therapy for advanced myeloid leukemia and MDS. Biol Blood Marrow Transplant. 2011 Jun;17(6):893-900. doi: 10.1016/j.bbmt.2010.09.022. Epub 2010 Oct 11.

  PMID: 20946966 RESULT

Related Links

• UT MD Anderson Cancer Website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Clofarabine; Busulfan; fludarabine; fludarabine phosphate; Bone Marrow Transplantation; thymoglobulin; Antilymphocyte Serum; Filgrastim; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Tissue 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; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Richard Champlin, MD / Professor, Chair, Stem Cell Transplantation
• Organization: University of Texas MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-3618

Study Officials

• Richard E. Champlin, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: May 3, 2007
• First Posted: May 4, 2007
• Study Start: September 1, 2006
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: January 26, 2021
• Results First Posted: January 26, 2021

Record last verified: 2021-01

Locations

US (1)