Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Total-Body Irradiation for the Treatment of Hematological Malignancies
NCT ID: NCT04195633
Last Updated: 2025-11-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
60 participants
INTERVENTIONAL
2021-01-25
2028-01-10
Brief Summary
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Detailed Description
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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
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
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
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.
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
Interventions
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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
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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.
6 Months
ALL
Yes
Sponsors
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medac GmbH
INDUSTRY
Fred Hutchinson Cancer Center
OTHER
Responsible Party
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Principal Investigators
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Filippo Milano
Role: PRINCIPAL_INVESTIGATOR
Fred Hutch/University of Washington Cancer Consortium
Locations
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Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Countries
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Central Contacts
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Facility Contacts
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Filippo Milano
Role: primary
Other Identifiers
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NCI-2019-07697
Identifier Type: REGISTRY
Identifier Source: secondary_id
10343
Identifier Type: OTHER
Identifier Source: secondary_id
RG1005742
Identifier Type: -
Identifier Source: org_study_id