PRO#1278: Fludarabine and Busulfan vs. Fludarabine, Busulfan and Total Body Irradiation

NCT01366612 | Terminated Phase 3 Results DMC

• 1 other identifier: PRO#1278: Flu-Bu-TBI
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single institution study of fludarabine and busulfan versus fludarabine, busulfan and low dose total body irradiation in patients undergoing allogeneic stem cell transplantation. A study population of 80 subjects will be enrolled from The John Theurer Cancer Center at Hackensack University Medical Center. Subjects who are eligible to receive allogeneic hematopoietic stem cell transplantation according to the eligibility criteria will be consented and enrolled. Subjects will be randomly assigned to receive one of 2 conditioning regimen: fludarabine and busulfan, or fludarabine busulfan and low dose total body irradiation (TBI). Subjects will be followed until 1 year post transplantation to assess the relapse rate in each arm and transplant-related toxicity. The combination of fludarabine and busulfan is the current standard of care for patients with myeloid malignancies (AML, CML and other myeloproliferative disorders, or MDS) undergoing allogeneic transplantation at HUMC. In this study we will be comparing in a randomized fashion the standard regimen to a regimen of fludarabine, busulfan and TBI.

Conditions

Myeloid Malignancies; Acute Myelogenous Leukemia; Chronic Myelogenous Leukemia; Myeloproliferative Disorders; Myelodysplastic Syndrome

Keywords

Allogeneic Stem Cell Transplant; AML; CML; MDS

Outcome Measures

Primary Outcomes (1)

• To Compare the Relapse Rate at 1 Year of Patients With Myeloid Malignancies Receiving Each Treatment

  1 year

Study Arms (2)

Group 1

ACTIVE COMPARATOR

FLUDARABINE AND BUSULFAN

Drug: Fludarabine and Busulfan plus/minus Total Body Irradiation (low dose)

Group 2

EXPERIMENTAL

FLUDARABINE, BUSULFAN AND LOW DOSE TOTAL BODY IRRADIATION

Drug: Fludarabine and Busulfan + Low Dose Total Body Irradiation (LD TBI)

Interventions

Fludarabine and Busulfan plus/minus Total Body Irradiation (low dose) DRUG

Fludarabine 40mg/m2 and Busulfan 130mg/m2 on days -6, -5, -4 and -3 of transplant. rATG on days -3, -2 and -1

Also known as: Fludara, Busulfex

Group 1

Fludarabine and Busulfan + Low Dose Total Body Irradiation (LD TBI) DRUG

Fludarabine 40mg/m2 and Busulfan 130mg/m2 on days -6, -5, -4 and -3 of transplant. rATG on days -3, -2 and -1 TBI 200cGY (as randomized) on day -1

Also known as: Fludara, Busulfex

Group 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of acute myelogenous leukemia, chronic myelogenous leukemia, other myeloproliferative disorder, or myelodysplastic syndrome
• Any stage of disease will be considered for transplantation
• Have a suitable related or unrelated donor (Section 3.3)
• Age ≥18 but \<70 yrs
• KPS of ≥70%
• Recovery from all hematologic and non-hematology toxicities from previous therapies.

You may not qualify if:

• Diagnosis other than acute myelogenous leukemia, myeloproliferative disorder, or myelodysplastic syndrome
• Chemotherapy or radiotherapy within 14 days of initiating treatment in this study with the exception of lenalidomide, decitabine, azacitidine, imatinib mesylate, dasatinib, nilotinib hydrochloride and hydroxyurea
• Prior dose-intense therapy requiring HSC support within 56 days of initiating treatment in this study
• Uncontrolled bacterial, viral, fungal or parasitic infections
• Uncontrolled CNS metastases
• Known amyloid deposition in heart
• Organ dysfunction
• LVEF \<40% or cardiac failure not responsive to therapy
• FVC, FEV1, or DLCO \<50% of predicted and/or receiving supplementary continuous oxygen
• Evidence of hepatic synthetic dysfunction, or total bilirubin \>2x or AST \>3x ULN
• Measured creatinine clearance \<20 ml/min
• Karnofsky score \<70%
• Life expectancy limited by another co-morbid illness
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
• Female subject is pregnant or breast-feeding (women) or unwilling to use acceptable birth control methods (men or women) for twelve months after treatment. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.

Sponsors & Collaborators

• Hackensack Meridian Health: lead

Study Sites (1)

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Related Publications (12)

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• de Lima M, Anagnostopoulos A, Munsell M, Shahjahan M, Ueno N, Ippoliti C, Andersson BS, Gajewski J, Couriel D, Cortes J, Donato M, Neumann J, Champlin R, Giralt S. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood. 2004 Aug 1;104(3):865-72. doi: 10.1182/blood-2003-11-3750. Epub 2004 Apr 15.

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  PMID: 40227676 DERIVED

MeSH Terms

Conditions

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

Interventions

fludarabine; fludarabine phosphate; Busulfan; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Radiotherapy; Therapeutics; Investigative Techniques

Results Point of Contact

• Title: Joshua Zenreich
• Organization: Hackensack Meridian Health

joshua.zenreich@hmhn.org

15519964248

Study Officials

• Michele Donato, MD

  Hackensack Meridian Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2011
• First Posted: June 6, 2011
• Study Start: June 16, 2010
• Primary Completion: August 17, 2020
• Study Completion: August 18, 2020
• Last Updated: March 9, 2026
• Results First Posted: December 16, 2022

Record last verified: 2026-02

Locations

US (1)