Busulfan, Fludarabine Phosphate, and Post-Transplant Cyclophosphamide in Treating Patients With Blood Cancer Undergoing Donor Stem Cell Transplant
Timed Sequential Busulfan and Post Transplant Cyclophosphamide for Allogeneic Transplantation
2 other identifiers
interventional
204
1 country
1
Brief Summary
This phase II trial studies the side effect of busulfan, fludarabine phosphate, and post-transplant cyclophosphamide in treating patients with blood cancer undergoing donor stem cell transplant. Drugs used in chemotherapy, such as busulfan, fludarabine phosphate and cyclophosphamide work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy such as busulfan and fludarabine phosphate before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving cyclophosphamide after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Aug 2016
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 5, 2016
CompletedStudy Start
First participant enrolled
August 5, 2016
CompletedFirst Posted
Study publicly available on registry
August 10, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 31, 2026
February 17, 2026
February 1, 2026
10.1 years
August 5, 2016
February 12, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Non-relapse mortality rate
The proportion of patients with non-relapse mortality will be reported separately by arm, along with the corresponding 95% Bayesian credible interval.
100 days
Secondary Outcomes (8)
Graft versus host disease-free survival/relapse free survival
Up to 3 years
Relapse-free survival
Up to 3 years
Overall survival
Up to 3 years
Non-relapse mortality
Up to 3 years
Relapse rate
Up to 3 years
- +3 more secondary outcomes
Study Arms (6)
Group I (haploidentical donor transplant, chemotherapy)
EXPERIMENTALPatients receive busulfan IV over 3 hours on days -13, -12, and -6 to -3, thiotepa IV over 4 hours on day -7, fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo stem cell transplantation IV on day 0. Patients then receive cyclophosphamide IV over 3 hours on days 3 and 4. Beginning on day 5, patients receive tacrolimus IV continuously or PO BID for up to 3 months and mycophenolate mofetil PO TID.
Group II (matched donor transplant, chemotherapy)
EXPERIMENTALPatients receive busulfan IV over 3 hours on days -13, -12, and -6 to -3, fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo stem cell transplantation IV on day 0. Patients then receive cyclophosphamide IV over 3 hours on days 3 and 4. Beginning on day 5, patients receive tacrolimus IV continuously or PO BID for up to 3 months.
Group III (haploidentical donor transplant, chemotherapy)
EXPERIMENTALPatients receiving haploidentical related donor transplant, diagnosis of myelofibrosis, \> 60 years old, or patients with comorbidity scores \> 3 will go in Group 3 or 4. If patients with comorbidity score \> 3, then the principal investigator is the final arbiter of eligibility for comorbidity score \> 3. Busulfan is administered at the dose calculated to achieve a total (including first two doses delivered on day -20 and day -13) system exposure of 20,000 +/- 12% uMol-min based on the pharmacokinetic studies.
Group IV (matched donor transplant, chemotherapy)
EXPERIMENTALPatients receiving haploidentical related donor transplant, diagnosis of myelofibrosis, \> 60 years old, or patients with comorbidity scores \> 3 will go in Group 3 or 4. If patients with comorbidity score \>3, then the principal investigator is the final arbiter of eligibility for comorbidity score \> 3. Busulfan is administered at the dose calculated to achieve a total (including first two doses delivered on day -20 and day -13) system exposure of 20,000 +/- 12% uMol-min based on the pharmacokinetic studies.
Group V (haploidentical donor transplant, chemotherapy)
EXPERIMENTALPatients receive busulfan IV over 3 hours on days -20, -13, and -6 to -3, a lower dose of thiotepa IV over 4 hours on day -7, fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo stem cell transplantation IV on day 0. Patients then receive cyclophosphamide IV over 3 hours on days 3 and 4. Beginning on day 5, patients receive tacrolimus IV continuously or PO BID for up to 3 months and mycophenolate mofetil PO TID.
Group VI (matched or haploidentical transplant, chemotherapy)
EXPERIMENTALPatients receiving fully matched or haploidentical donor transplant receive busulfan IV over 3 hours on days -20, -13, and -6 to -3, a lower dose of thiotepa IV over 4 hours on day -7, fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo stem cell transplantation IV on day 0. Patients then receive cyclophosphamide IV over 3 hours on days 3 and 4. Beginning on day 5, patients receive tacrolimus IV continuously or PO BID for up to 3 months and mycophenolate mofetil PO TID.
Interventions
Undergo stem cell transplantation
Given IV
Given IV
Given IV
Given IV
Correlative studies
Given PO
Correlative studies
Given IV or PO
Given IV
Eligibility Criteria
You may qualify if:
- Patients with high-risk hematologic malignancies with anticipated poor prognosis with non transplant therapy, including those in remission or with induction failure and after treated or untreated relapse; Diagnoses to be included a) Acute myeloid leukemia; b) Acute lymphocytic leukemia; c) Chronic myeloid leukemia; d) Chronic lymphoproliferative disorder; e) Myelodysplastic syndrome; f) Myeloproliferative syndromes; g) Non-Hodgkin's lymphoma; h) Hodgkin's Lymphoma; i) Multiple myeloma
- Patients must have a haploidentical related donor or a fully matched related or unrelated donor
- Performance score of \>= 70 by Karnofsky/Lansky or performance score (PS) 0 to 1 (Eastern Cooperative Oncology Group \[ECOG\] =\< 1)
- Left ventricular ejection fraction \>= 50%
- Adequate pulmonary function with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) \>= 50% of expected corrected for hemoglobin and/or volume; children unable to perform pulmonary function tests (e.g., less than 7 years old) pulse oximetry of \>= 92% on room air
- Creatinine clearance (calculated creatinine clearance by Cockcroft-Gault using adjusted body weight if actual body weight is 20% greater than ideal is permitted) should be \> 50 ml/min
- Bilirubin =\< 2 x the upper limit of normal (except with patients high indirect bilirubin due to Gilbert's syndrome, hypersplenism, or hemolysis)
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 200
- Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization; women of child bearing potential must be willing to use an effective contraceptive measure while on study
- Patient or patient's legal representative able to sign informed consent
You may not qualify if:
- Human immunodeficiency virus (HIV) seropositivity
- Uncontrolled infections
- Patients with comorbidity score \> 3; the principal investigator is the final arbiter of eligibility for comorbidity score \> 3
- Prior allogeneic transplant
- Patients with active hepatitis B and C
- Patients with prior coronary artery disease
- Patients who received inotuzumab and/or gemtuzumab in the past
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Popat UR, Pasvolsky O, Bassett R Jr, Mehta RS, Olson A, Chen J, Alousi AM, Al-Atrash G, Bashir Q, Gulbis AM, Hosing CM, Im JS, Kebriaei P, Khouri I, Marin D, Nieto Y, Oran B, Saini N, Shigle TL, Srour SA, Ramdial JL, Rezvani K, Qazilbash MH, Andersson BS, Champlin RE, Shpall EJ. Myeloablative fractionated busulfan for allogeneic stem cell transplant in older patients or patients with comorbidities. Blood Adv. 2023 Oct 24;7(20):6196-6205. doi: 10.1182/bloodadvances.2023010850.
PMID: 37611156DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Uday R Popat, MD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 5, 2016
First Posted
August 10, 2016
Study Start
August 5, 2016
Primary Completion (Estimated)
August 31, 2026
Study Completion (Estimated)
August 31, 2026
Last Updated
February 17, 2026
Record last verified: 2026-02