Acute Myelogenous Leukemia, Chronic Myelogenous Leukemia, Myelodysplastic Syndrome, Myeloid Malignancies, Myeloproliferative Disorders
Conditions
Keywords
Allogeneic Stem Cell Transplant, AML, CML, MDS
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
Interventions
DRUGFludarabine and Busulfan plus/minus Total Body Irradiation (low dose)
Fludarabine 40mg/m2 and Busulfan 130mg/m2 on days -6, -5, -4 and -3 of transplant. rATG on days -3, -2 and -1
DRUGFludarabine and Busulfan + Low Dose Total Body Irradiation (LD TBI)
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
Sponsors
Hackensack Meridian Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To Compare the Relapse Rate at 1 Year of Patients With Myeloid Malignancies Receiving Each Treatment | 1 year |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichele Donato, MD
Hackensack Meridian Health
Participant flow
Pre-assignment details
Of the 53 consented, Forty-Seven patients with myeloid diseases were randomized into Flu/Bu4 (25 patients) or Flu/Bu4/TBI (22 patients)
Participants by arm
| Arm | Count |
|---|---|
| Group 1 FLUDARABINE AND BUSULFAN
Fludarabine and Busulfan plus/minus Total Body Irradiation (low dose): Fludarabine 40mg/m2 and Busulfan 130mg/m2 on days -6, -5, -4 and -3 of transplant.
rATG on days -3, -2 and -1 | 25 |
| Group 2 FLUDARABINE, BUSULFAN AND LOW DOSE TOTAL BODY IRRADIATION
Fludarabine and Busulfan + Low Dose Total Body Irradiation (LD TBI): 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 | 22 |
| Total | 47 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 22 Participants | 47 Participants |
| Age, Continuous | 48.4 Years | 48.8 Years | 48.6 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 19 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 18 Participants | 19 Participants | 37 Participants |
| Region of Enrollment United States | 25 participants | 22 participants | 47 participants |
| Sex: Female, Male Female | 11 Participants | 8 Participants | 19 Participants |
| Sex: Female, Male Male | 14 Participants | 14 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 25 | 8 / 22 |
| other Total, other adverse events | 0 / 25 | 0 / 22 |
| serious Total, serious adverse events | 18 / 25 | 16 / 22 |
Outcome results
Primary
To Compare the Relapse Rate at 1 Year of Patients With Myeloid Malignancies Receiving Each Treatment
Time frame: 1 year
Population: Relapse Rate was analyzed in 34 patients with AML
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | To Compare the Relapse Rate at 1 Year of Patients With Myeloid Malignancies Receiving Each Treatment | 38.9 Percent |
| Group 2 | To Compare the Relapse Rate at 1 Year of Patients With Myeloid Malignancies Receiving Each Treatment | 18.8 Percent |