NCT02861417

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

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 204 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 12 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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.

Conditions

• Hematopoietic and Lymphoid Cell Neoplasm
• High Risk Acute Myeloid Leukemia
• High Risk Myelodysplastic Syndrome
• Lymphoproliferative Disorder
• Myelodysplastic Syndrome
• Myelodysplastic/Myeloproliferative Neoplasm
• Recurrent Acute Lymphoblastic Leukemia
• Recurrent Acute Myeloid Leukemia
• Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Recurrent High Risk Myelodysplastic Syndrome
• Recurrent Hodgkin Lymphoma
• Recurrent Myelodysplastic Syndrome
• Recurrent Non-Hodgkin Lymphoma
• Recurrent Plasma Cell Myeloma

Interventions

Type	Name	Description
PROCEDURE	Allogeneic Hematopoietic Stem Cell Transplantation	Undergo stem cell transplantation
DRUG	Busulfan	Given IV
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine	Given IV
DRUG	Fludarabine Phosphate	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Mycophenolate Mofetil	Given PO
OTHER	Pharmacological Study	Correlative studies
DRUG	Tacrolimus	Given IV or PO
DRUG	Thiotepa	Given IV

Timeline

• Start date: 2016-08-05
• Primary completion: 2026-08-31
• Completion: 2026-08-31
• First posted: 2016-08-10
• Last updated: 2026-02-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study