A Phase 2 interventional study of Allogeneic Hematopoietic Stem Cell Transplantation and Busulfan in Hematopoietic and Lymphoid Cell Neoplasm, High Risk Acute Myeloid Leukemia and High Risk Myelodysplastic Syndrome, sponsored by M.D. Anderson Cancer Center. Active, not recruiting at 1 site in United States. Open to participants aged 12 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-08-06.
Sponsored by M.D. Anderson Cancer Center · Phase 2, Interventional, and Treatment
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.
PRIMARY OBJECTIVE:
I. To assess safety of timed sequential busulfan and fludarabine conditioning regimen and post transplant cyclophosphamide as determined by day 100 non-relapse mortality in patients undergoing allogeneic transplantation: from matched donors; from mismatched (haploidentical) donors.
SECONDARY OBJECTIVE:
I. To evaluate efficacy of this therapy and to compare outcomes between recipients of matched and mismatched donors by studying the following endpoints: graft versus host disease (GVHD)-free/relapse free survival; relapse-free survival; overall survival; non-relapse mortality; relapse rate; time to neutrophil and platelet engraftment; incidence of acute and chronic GVHD; grade 3 and 4 adverse events.
TERTIARY OBJECTIVE:
I. To study impact of timed sequential busulfan therapy and post-transplant cyclophosphamide on immune reconstitution and cytokines levels post-transplant.
OUTLINE: Patients are assigned to 1 of 4 groups.
GROUP I (FROM HAPLOIDENTICAL DONOR): Patients receive busulfan intravenously (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 orally (PO) twice daily (BID) for up to 3 months and mycophenolate mofetil PO thrice daily (TID).
GROUP II (FROM MATCHED DONOR): Patients 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 and GROUP IV: Patients 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 and GROUP VI: Patients 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.
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Exclusion Criteria:
Patients 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.
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation · Drug: Busulfan · Drug: Cyclophosphamide · Drug: Fludarabine · Drug: Fludarabine Phosphate · Other: Laboratory Biomarker Analysis · Drug: Mycophenolate Mofetil · Other: Pharmacological Study · Drug: Tacrolimus · Drug: Thiotepa
Patients 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.
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation · Drug: Busulfan · Drug: Cyclophosphamide · Drug: Fludarabine · Drug: Fludarabine Phosphate · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study · Drug: Tacrolimus
Patients 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.
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation · Drug: Busulfan · Drug: Cyclophosphamide · Drug: Fludarabine · Drug: Fludarabine Phosphate · Other: Laboratory Biomarker Analysis · Drug: Mycophenolate Mofetil · Other: Pharmacological Study · Drug: Tacrolimus · Drug: Thiotepa
Patients 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.
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation · Drug: Busulfan · Drug: Cyclophosphamide · Drug: Fludarabine · Drug: Fludarabine Phosphate · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study · Drug: Tacrolimus
Patients 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.
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation · Drug: Busulfan · Drug: Cyclophosphamide · Drug: Fludarabine · Drug: Fludarabine Phosphate · Other: Laboratory Biomarker Analysis · Drug: Mycophenolate Mofetil · Other: Pharmacological Study · Drug: Tacrolimus · Drug: Thiotepa
Patients 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.
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation · Drug: Busulfan · Drug: Cyclophosphamide · Drug: Fludarabine · Drug: Fludarabine Phosphate · Other: Laboratory Biomarker Analysis · Drug: Mycophenolate Mofetil · Other: Pharmacological Study · Drug: Tacrolimus · Drug: Thiotepa
Undergo stem cell transplantation
Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT
Given IV
Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508
Given IV
Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719
Given IV
Also known as: Fluradosa
Given IV
Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586
Correlative studies
Given PO
Also known as: Cellcept, MMF
Correlative studies
Given IV or PO
Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic
Given IV
Also known as: 1,1'',1''''-Phosphinothioylidynetrisaziridine, Girostan, N,N'', N''''-Triethylenethiophosphoramide, Oncotiotepa, STEPA, Tepadina, TESPA, Tespamin, Tespamine, Thio-Tepa, Thiofosfamide, Thiofozil, Thiophosphamide, Thiophosphoramide, Thiotef, Tifosyl, TIO TEF, Tio-tef, Triethylene thiophosphoramide, Triethylenethiophosphoramide, Tris(1-aziridinyl)phosphine sulfide, TSPA, WR 45312
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.
Time frame: 100 days
Graft versus host disease-free survival/relapse free survival
Will be calculated from the time of transplant by the method of Kaplan and Meier. Patients with matched donors will be compared to patients with mismatched donors by the log-rank test. Cox proportional hazards regression analysis will be used to assess the association between these survival parameters and clinical and treatment covariates of interest.
Time frame: Up to 3 years
Relapse-free survival
Will be calculated from the time of transplant by the method of Kaplan and Meier. Patients with matched donors will be compared to patients with mismatched donors by the log-rank test. Cox proportional hazards regression analysis will be used to assess the association between these survival parameters and clinical and treatment covariates of interest.
Time frame: Up to 3 years
Overall survival
Will be calculated from the time of transplant by the method of Kaplan and Meier. Patients with matched donors will be compared to patients with mismatched donors by the log-rank test. Cox proportional hazards regression analysis will be used to assess the association between these survival parameters and clinical and treatment covariates of interest.
Time frame: Up to 3 years
Non-relapse mortality
The proportion of patients with non-relapse mortality will be reported separately by arm, along with the corresponding 95% Bayesian credible interval.
Time frame: Up to 3 years
Relapse rate
Will be observed.
Time frame: Up to 3 years
Time to platelet and neutrophil engraftment
Will be calculated from the time of transplant and estimated by the Kaplan-Meier method. Distributions will be compared between patients with matched and mismatched donors via the log-rank test.
Time frame: Up to 3 years
Incidence of acute and chronic graft versus host disease
Will be estimated using the method of Gooley, and the method of Fine and Gray will be used to model the incidence by disease and clinical characteristics of interest, including matched versus mismatched donors.
Time frame: Up to 3 years
Incidence of grade 3 and 4 adverse events
Descriptive statistics will be used to summarize adverse events by treatment arm. The number and proportion of subjects with treatment emergent adverse events will be reported and compared between patients with matched and mismatched donors by using Fisher's exact test. Frequency counts and percentages will also be presented of subjects with serious adverse events and adverse events leading to withdrawal. Graphical summaries will be used where appropriate.
Time frame: Up to 3 years
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M.D. Anderson Cancer Center