NCT04195633

Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Total-Body Irradiation for the Treatment of Hematological Malignancies

Hematopoietic Stem Cell Transplantation From Haploidentical Donors in Patients With Hematological Malignancies Using a Treosulfan-Based Preparative Regimen

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 6 Months
• Healthy volunteers: Accepted

Summary

This phase II trial studies how well a donor stem cell transplant, treosulfan, fludarabine, and total-body irradiation work in treating patients with blood cancers (hematological malignancies). Giving chemotherapy and total-body irradiation 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. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.

Detailed description

OUTLINE: Patients are assigned to 1 of 2 arms. ARM A (HIGH DOSE TREOSULFAN): Patients receive high dose treosulfan intravenously (IV) over 120 minutes on days -6 to -4 and fludarabine IV over 60 minutes on days -6 to -2. Patients then undergo total-body irradiation on day -1 and allogeneic hematopoietic stem cell transplantation on day 0. Patients then receive cyclophosphamide IV over 1-2 hours on days 3-4. Beginning on day 5, patients receive cyclosporine IV twice daily (BID) or three times daily (TID) over 1-2 hours or orally (PO) (after 3 months, in the absence of GVHD, cyclosporine tapering will start by 5-10% per week, until drug withdrawal at 6 months post-transplant). Beginning on day 5, patients also receive mycophenolate sodium PO TID or mycophenolate mofetil IV or PO TID until day 35 (may be continued if active GVHD is present). Beginning on day 5, patients also receive filgrastim until the absolute neutrophil count is \> 1,000/uL for 3 consecutive days. Additionally, patients undergo bone marrow aspiration and biopsy, and echocardiography at baseline and blood sample collection and computed tomography (CT) or positron emission tomography (PET)/CT on study. ARM B (LOW DOSE TREOSULFAN): Patients receive low dose treosulfan IV over 120 minutes on days -6 to -4 and fludarabine IV over 60 minutes on days -6 to -2. Patients then undergo total-body irradiation and allogeneic hematopoietic stem cell transplantation, and receive cyclophosphamide, cyclosporine, mycophenolate sodium or mycophenolate mofetil, and filgrastim as in Arm A. Additionally, patients undergo bone marrow aspiration and biopsy, and echocardiography at baseline and blood sample collection and CT or PET/CT on study. After completion of transplant, patients are followed up at 28, 56, 84, 365, and 730 days.

Conditions

• Acute Leukemia
• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Adult Diffuse Large Cell Lymphoma
• Anaplastic Large Cell Lymphoma
• Burkitt Lymphoma
• Chronic Myeloid Leukemia, BCR-ABL1 Positive
• Chronic Myelomonocytic Leukemia
• Hodgkin Lymphoma
• Lymphoblastic Lymphoma
• Lymphoplasmacytic Lymphoma
• Mantle Cell Lymphoma
• Mixed Phenotype Acute Leukemia
• Myelodysplastic Syndrome
• Prolymphocytic Leukemia
• Refractory Chronic Lymphocytic Leukemia
• Refractory Follicular Lymphoma
• Refractory Marginal Zone Lymphoma
• Refractory Small Lymphocytic Lymphoma

Interventions

Type	Name	Description
PROCEDURE	Allogeneic Hematopoietic Stem Cell Transplantation	Undergo allogeneic hematopoietic stem cell transplantation
DRUG	Cyclophosphamide	Given IV
DRUG	Cyclosporine	Given IV or PO
BIOLOGICAL	Filgrastim	Given IV
DRUG	Fludarabine	Given IV
DRUG	Mycophenolate Mofetil	Given IV or PO
DRUG	Mycophenolate Sodium	Given PO
RADIATION	Total-Body Irradiation	Undergo total-body irradiation
DRUG	Treosulfan	Given IV
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy
PROCEDURE	Echocardiography Test	Undergo echocardiography
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT or PET/CT
PROCEDURE	Positron Emission Tomography	Undergo PET/CT

Timeline

• Start date: 2021-01-25
• Primary completion: 2027-04-15
• Completion: 2029-03-12
• First posted: 2019-12-12
• Last updated: 2026-02-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study