Recruiting

Phase 2

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

Sponsor:

Fred Hutchinson Cancer Center

Code:

NCT04195633

Conditions

Acute Leukemia

Acute Lymphoblastic Leukemia

Acute Myeloid Leukemia

Adult Diffuse Large Cell Lymphoma

Anaplastic Large Cell Lymphoma

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Accepted

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation

Cyclophosphamide

Cyclosporine

Filgrastim

Fludarabine

Study Details

Brief 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.

Conditions

Acute Leukemia

Acute Lymphoblastic Leukemia

Acute Myeloid Leukemia

Adult Diffuse Large Cell Lymphoma

Anaplastic Large Cell Lymphoma

Study ID

NCT04195633

Start date

Jan 25, 2021

Status verified date

May, 2026

Completion date

Mar 12, 2029

Anticipated

Primary completion date

Apr 15, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Accepted

Inclusion Criteria:

Acute leukemia (AL) that includes acute myeloid leukemia (AML) / acute lymphoblastic leukemia (ALL) / mixed phenotype leukemia (MPAL) in complete morphological remission (CR) with or without detectable minimal residual disease (MRD); complete morphological remission is defined by the presence of less than 5% of detectable blasts in bone marrow specimen, evaluated per standard of care. Patients with documented CR but without hematologic recovery since last chemotherapy are considered eligible to the study
Chronic myelogenous leukemia (CML), except refractory blast crisis. To be eligible in first chronic phase, patients must have failed or be intolerant to at least one tyrosine-kinase inhibitor
Chronic myelomonocytic leukemia (CMML)
Myelodysplastic syndromes (MDS)
Lymphoblastic, Burkitt's and other high-grade lymphoma in any complete (CR) or partial (PR) response

CR and PR are defined according to Lugano classification: Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
Low grade lymphoma (chronic lymphocytic leukemia \[CLL\]/small lymphocytic lymphoma \[SLL\], marginal zone lymphoma, follicular lymphoma) progressed after two treatment regimens, in CR/PR

For CLL/SLL, CR and PR are defined according to: International Workshop on CLL (iwCLL) guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL
CR and PR are defined according to Lugano classification: Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
Large cell lymphoma in > second CR (CR2)/ >= PR2

CR and PR are defined according to Lugano classification: Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
Mantle cell lymphoma, lymphoplasmacytic lymphoma and prolymphocytic leukemia may be eligible after initial therapy if in CR/PR

CR and PR are defined according to Lugano classification: Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
For prolymphocytic leukemia (PLL), CR is defined as a normalization of lymphadenopathies (long-axis diameter < 1 cm) and splenomegaly (< 13 cm), absence of constitutional symptoms, PLL cells < 5% in bone marrow and circulating lymphocytes count < 4 x 10\^9/L. Patients without hematopoietic recovery are considered eligible to the study. PR is defined as a decrease of >= 30% of the sum of lymphadenopathies' long-axis diameters, a decrease of >= 50% in spleen vertical length beyond normal from baseline, peripheral blood (PB) lymphocytes =< 30 x 10\^9/L (and a decrease of >= 50% from baseline)
Hodgkin Lymphoma in > CR2/PR2

CR and PR are defined according to Lugano classification: Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
Subjects must be >= 6 months old
Karnofsky >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1 (for adults)
Lansky score >= 50 (for children)
Adequate cardiac function defined as absence of decompensated congestive heart failure or uncontrolled arrhythmia AND left ventricular ejection fraction >= 40% or shortening fraction > 22%
Adequate pulmonary function defined as absence of oxygen (O2) requirements and one of the following:

Diffusion capacity of the lung for carbon monoxide (DLCO) corrected >= 70% mm Hg
DLCO corrected between 60% - 69% mm Hg and partial pressure of oxygen (pO2) >= 70 mm Hg
DLCO corrected between 50% - 59% mm Hg and pO2 >= 80 mm Hg Pediatric patients unable to perform pulmonary function tests must have O2 saturation >= 92% on room air. May not be on supplemental oxygen
Total bilirubin < 2 x upper limit of normal (ULN) unless felt to be related to Gilbert's disease or hemolysis
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
Alkaline phosphatase =< 5 x ULN
Creatinine < 2.0 mg/dl (adults) or estimated creatinine clearance > 40 ml/min (pediatrics)

All adults with a creatinine > 1.2 or a history of renal dysfunction must have estimated creatinine clearance > 40 ml/min
If recent mold infection, e.g., aspergillus, must be cleared by infectious disease to proceed
Patients who have undergone prior allogeneic hematopoietic cell transplant are eligible, but the prior transplant must have been performed at least 3 months prior to enrollment, unless in case of graft failure from the prior transplant
Written and signed informed consent
DONOR: Donors must be haploidentical relatives of the patients. Donor-recipient compatibility will be tested through HLA typing at high resolution for the HLA loci (-A, -B, -C, -DRB1, -DQB1). Donor and recipient should share at least 5/10 HLA loci
DONOR: Age >= 12 years
DONOR: Weight >= 40 Kg
DONOR: Ability of donors younger than 18 years of age to undergo apheresis without use of a vascular access device. Vein check must be performed and verified by an apheresis nurse prior to arrival.
DONOR: Donor must meet selection criteria as defined by the Foundation of the Accreditation of Cell Therapy (FACT) and will be screened per the American Association of Blood Banks (AABB) guidelines
DONOR: In case of more available haploidentical donors, selection criteria should include, in this order:

For cytomegalovirus (CMV) seronegative recipients, a CMV seronegative donor
Red blood cell compatibility

Red blood cell (RBC) cross match compatible
Minor ABO incompatibility
Major ABO incompatibility

Exclusion Criteria:

Active, uncontrolled, life-threatening viral, bacterial or fungal infection requiring treatment at time of conditioning regiment administration and transplantation
Presence of a malignancy other than the one for which the transplant is being performed, with an expected survival less than 75% at 5 years
Pregnant or breastfeeding
Known hypersensitivity to treosulfan, fludarabine or cyclophosphamide
Dosing with another investigational agent within 30 days prior to entry in the study
Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy and/or cranial radiation prior to initiation of conditioning (day -6)
DONOR: Since detection of anti-donor-specific-antigen antibodies (anti-DSA) is associated with higher graft rejection rate, patients will be screened for anti-DSA pre-transplant. Patients with DSA mean fluorescent intensity (MFI) < 5000 after desensitization treatment, will be considered eligible to participate in the study. The first 10 subjects enrolled in the trial will be DSA-negative.

Study Design

Enrollment

60 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A (high dose treosulfan)

Patients receive high 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 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 BID or TID over 1-2 hours or 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 CT or PET/CT on study.

experimental: 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.

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation

Undergo allogeneic hematopoietic stem cell transplantation

Cyclophosphamide

Given IV

Cyclosporine

Given IV or PO

Filgrastim

Given IV

Fludarabine

Given IV

Mycophenolate Mofetil

Given IV or PO

Mycophenolate Sodium

Given PO

Total-Body Irradiation

Undergo total-body irradiation

Treosulfan

Given IV

Bone Marrow Aspiration

Undergo bone marrow aspiration

Bone Marrow Biopsy

Undergo bone marrow biopsy

Echocardiography Test

Undergo echocardiography

Biospecimen Collection

Undergo blood sample collection

Computed Tomography

Undergo CT or PET/CT

Positron Emission Tomography

Undergo PET/CT

Primary outcome measure

Graft failure/rejection [ Time Frame: Up to 2 years post-transplant ]

Central Contacts and Locations

Central contacts

Phuong Vo, MD

206-667-2749 ptvo@fredhutch.org

Locations

Fred Hutch/University of Washington Cancer Consortium

Recruiting

Seattle, Washington, United States, 98109

Contacts

Phuong Vo, MD

206-667-2749 ptvo@fredhutch.org

Principal Investigator:

Phuong Vo, MD

More Information

Sponsor

Fred Hutchinson Cancer Center

Last update posted

May 29, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Fred Hutchinson Cancer Center on 2026-05-29.