ClinicalTrials.gov record 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
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Phase II, open-label study testing a treosulfan-based conditioning regimen (given with fludarabine and total-body irradiation) before haploidentical donor stem cell transplantation. Participants are assigned to one of two arms (high-dose or low-dose treosulfan) and receive post-transplant medications. Follow-up includes visits and outcomes tracked up to two years.
What it is studying. How a treosulfan-based preparative regimen (high versus low treosulfan dose), given with fludarabine and total-body irradiation, performs when used before a haploidentical donor hematopoietic stem cell transplant.
What the researchers hope to learn. Primary scientific goal: measure graft failure/rejection after treosulfan-based conditioning. Secondary goals: measure overall survival, progression-free survival, non-relapse mortality, relapse, acute and chronic graft-versus-host disease, clinically significant infections, and platelet engraftment up to two years.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Cyclophosphamide
- Cyclosporine
- Fludarabine
- Mycophenolate Mofetil
- Mycophenolate Sodium
- Treosulfan
- Biological
- Filgrastim
- Procedure
- Allogeneic Hematopoietic Stem Cell Transplantation
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
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 description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
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.
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AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants receive a preparative regimen (treosulfan and fludarabine), total‑body irradiation, then an allogeneic haploidentical stem‑cell transplant and post‑transplant medicines (cyclophosphamide, cyclosporine, mycophenolate; filgrastim for white blood cell recovery). They will have bone‑marrow aspiration and biopsy, blood draws, baseline echocardiogram, and CT or PET/CT scans as part of the study. Follow‑up visits and monitoring occur at about days 28, 56, 84, 365 and 730 after transplant to check graft status, infections, graft‑versus‑host disease, and blood counts. Donor testing and apheresis are performed for the required haploidentical relative donor per donor eligibility rules.
How the study is structured. Interventional Phase 2 study with two parallel, non-randomized treatment arms (high-dose treosulfan vs low-dose treosulfan). Open-label (no masking). All participants receive haploidentical donor stem cell transplant plus standardized post-transplant drugs and monitoring; key outcomes are assessed up to two years.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Waldenström macroglobulinemia
Important dates
- Study start
- Jan 25, 2021
- Primary completion
- Apr 15, 2027 (estimated)
- Study completion
- Mar 12, 2029 (estimated)
- Target enrollment
- 60 participants (estimated)
- Last updated on registry
- May 29, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Fred Hutchinson Cancer Center
- Collaborators
- medac GmbH
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Phuong Vo, MD 📞 206-667-2749 ✉ ptvo@fredhutch.org
Participating sites (1)
- Fred Hutch/University of Washington Cancer ConsortiumRecruiting
Seattle, Washington, 98109 · United States
- Phuong Vo, MD · 206-667-2749 · ptvo@fredhutch.org
- Phuong Vo, MD
Terms used on this page · explanations by MedicalUpdates.ai
- stem cell transplant
- A procedure that replaces blood-forming cells after high-dose treatment. 'Autologous' uses the person's own cells collected beforehand; 'allogeneic' uses cells from a donor.
- minimal residual disease
- Very small amounts of disease that remain after treatment and can only be found with highly sensitive tests. 'MRD-negative' means none was detected at the test's limit. The exact test and threshold depend on the condition and the study.
- standard of care
- Treatment generally considered appropriate for a condition in a particular clinical setting. It can vary by patient, place and over time. In many studies the new treatment is added to, or compared with, standard of care.
- refractory
- A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
- baseline
- Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
- Karnofsky
- A scale from 100 (no complaints) down to 0 that describes how well a person can carry out daily activities. Studies often require a minimum score.
- ECOG
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- DLCO
- A breathing test that measures how well the lungs pass oxygen from the air into the blood.
- upper limit of normal
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- creatinine clearance
- A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- investigational agent
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- intrathecal
- Given by injection into the fluid around the spinal cord, usually through a lumbar puncture.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- absolute neutrophil count
- The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
- biopsy
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
- echocardiography
- An ultrasound scan of the heart. A transesophageal echocardiogram is done through a probe passed into the food pipe for a closer view.
- computed tomography
- An X-ray scan that builds detailed cross-section images of the body. 'High-resolution' CT (HRCT) is used to look closely at the lungs.
- positron emission tomography
- A scan in which a small amount of a radioactive tracer is injected so that activity in tissues can be seen. Often combined with a CT or MRI scan.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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