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

Primary Purpose

Myeloid Malignancies, Acute Myelogenous Leukemia, Chronic Myelogenous Leukemia

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Fludarabine and Busulfan plus/minus Total Body Irradiation (low dose)
Fludarabine and Busulfan + Low Dose Total Body Irradiation (LD TBI)
Sponsored by
Hackensack Meridian Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myeloid Malignancies focused on measuring Allogeneic Stem Cell Transplant, AML, CML, MDS

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Documented hypersensitivity to fludarabine or melphalan or to bortezomib, boron or mannitol or any components of the formulation
  • Patients unable or unwilling to provide consent
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant
  • Patient has received other investigational drugs with 14 days before enrollment
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study

Donor Inclusion and Exclusion Criteria

Donor Inclusion Criteria:

HLA 6/6 (HLA-A, B, DrB1) related donor or 7/8 (HLA-A, B, C, DrB1) unrelated donor Related donors will be evaluated in accordance with HUMC standard practice guidelines for the evaluation and management of allogeneic donors Unrelated donors will be identified, evaluated, and managed in accordance with National Marrow Donor Program standards Age ≥18 and <70 yrs KPS of ≥70% Willing to donate bone marrow using standard techniques or peripheral blood HSC by leukapheresis Have adequate veins for apheresis or agree to placement of a central venous catheter (femoral, subclavian) if donating peripheral blood HSC

Donor Exclusion Criteria Identical twin Female donors who are pregnant or breastfeeding Infection with HIV or viral hepatitis (B or C) Known allergy to filgrastim Current serious systemic illness Uncontrolled bacterial, viral, or fungal infection Receiving experimental therapy or investigational agents History of cancer other than treated basal cell cancer of the skin or carcinoma in situ of the cervix. Cancer treated with curative intent >5 yrs before donation will be reviewed on a case-by-case basis by the principal investigator

Sites / Locations

  • John Theurer Cancer Center at Hackensack University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Group 1

Group 2

Arm Description

FLUDARABINE AND BUSULFAN

FLUDARABINE, BUSULFAN AND LOW DOSE TOTAL BODY IRRADIATION

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
June 2, 2011
Last Updated
June 9, 2023
Sponsor
Hackensack Meridian Health
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1. Study Identification

Unique Protocol Identification Number
NCT01366612
Brief Title
PRO#1278: Fludarabine and Busulfan vs. Fludarabine, Busulfan and Total Body Irradiation
Acronym
FLUBUTBI
Official Title
PRO#1278: A Phase III Study of Fludarabine and Busulfan Versus Fludarabine, Busulfan and Low Dose Total Body Irradiation in Patients Receiving an Allogeneic Hematopoietic Stem Cell Transplant
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Lack of Accrual
Study Start Date
June 16, 2010 (Actual)
Primary Completion Date
August 17, 2020 (Actual)
Study Completion Date
August 18, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hackensack Meridian Health

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
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 (myelogenous leukemia, chronic myelogenous leukemia, other myeloproliferative disorder, or myelodysplastic syndrome) 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. Primary Objective The primary objective is to compare the relapse rate at 1 year of patients with myeloid malignancies receiving each regimen. Secondary Objectives The secondary objective is to compare the toxicity of each regimen

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myeloid Malignancies, Acute Myelogenous Leukemia, Chronic Myelogenous Leukemia, Myeloproliferative Disorders, Myelodysplastic Syndrome
Keywords
Allogeneic Stem Cell Transplant, AML, CML, MDS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Active Comparator
Arm Description
FLUDARABINE AND BUSULFAN
Arm Title
Group 2
Arm Type
Experimental
Arm Description
FLUDARABINE, BUSULFAN AND LOW DOSE TOTAL BODY IRRADIATION
Intervention Type
Drug
Intervention Name(s)
Fludarabine and Busulfan plus/minus Total Body Irradiation (low dose)
Other Intervention Name(s)
Fludara, Busulfex
Intervention Description
Fludarabine 40mg/m2 and Busulfan 130mg/m2 on days -6, -5, -4 and -3 of transplant. rATG on days -3, -2 and -1
Intervention Type
Drug
Intervention Name(s)
Fludarabine and Busulfan + Low Dose Total Body Irradiation (LD TBI)
Other Intervention Name(s)
Fludara, Busulfex
Intervention Description
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
Primary Outcome Measure Information:
Title
To Compare the Relapse Rate at 1 Year of Patients With Myeloid Malignancies Receiving Each Treatment
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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. Documented hypersensitivity to fludarabine or melphalan or to bortezomib, boron or mannitol or any components of the formulation Patients unable or unwilling to provide consent Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant Patient has received other investigational drugs with 14 days before enrollment Serious medical or psychiatric illness likely to interfere with participation in this clinical study Donor Inclusion and Exclusion Criteria Donor Inclusion Criteria: HLA 6/6 (HLA-A, B, DrB1) related donor or 7/8 (HLA-A, B, C, DrB1) unrelated donor Related donors will be evaluated in accordance with HUMC standard practice guidelines for the evaluation and management of allogeneic donors Unrelated donors will be identified, evaluated, and managed in accordance with National Marrow Donor Program standards Age ≥18 and <70 yrs KPS of ≥70% Willing to donate bone marrow using standard techniques or peripheral blood HSC by leukapheresis Have adequate veins for apheresis or agree to placement of a central venous catheter (femoral, subclavian) if donating peripheral blood HSC Donor Exclusion Criteria Identical twin Female donors who are pregnant or breastfeeding Infection with HIV or viral hepatitis (B or C) Known allergy to filgrastim Current serious systemic illness Uncontrolled bacterial, viral, or fungal infection Receiving experimental therapy or investigational agents History of cancer other than treated basal cell cancer of the skin or carcinoma in situ of the cervix. Cancer treated with curative intent >5 yrs before donation will be reviewed on a case-by-case basis by the principal investigator
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michele Donato, MD
Organizational Affiliation
Hackensack Meridian Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
John Theurer Cancer Center at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States

12. IPD Sharing Statement

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

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