Acute LeukemiaPhase 2NCT04195633
Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Total-Body Irradiation for the Treatment of Hematological Malignancies
A Phase 2 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Cyclosporine in people with Acute Leukemia and Acute Lymphoblastic Leukemia, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 6 months and olderHealthy volunteers can take part
- Conditions the study is for
- Acute Leukemia, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
- What is being tested?
- Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Cyclosporine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jan 2021to 12 Mar 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
Phuong Vo, MD, 206-667-2749, ptvo@fredhutch.org
Phuong Vo, MD
About this study
Official title: Hematopoietic Stem Cell Transplantation From Haploidentical Donors in Patients With Hematological Malignancies Using a Treosulfan-Based Preparative Regimen
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.
Read the 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
- Being tested
- Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide, Cyclosporine, Filgrastim, Fludarabine
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Large-Cell, Anaplastic, Burkitt Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myelomonocytic, Chronic, Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT
Undergo allogeneic hematopoietic stem cell transplantation
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
CyclosporineDrug
Also called 27-400, Ciclosporin, CsA, Cyclosporin
Given IV or PO
FilgrastimBiological
Also called G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
Given IV
FludarabineDrug
Also called Fluradosa
Given IV
Also called Cellcept, MMF
Given IV or PO
Mycophenolate SodiumDrug
Also called ERL 080, ERL 080A, Socium Mycophenolate
Given PO
Total-Body IrradiationRadiation
Also called TBI, Total Body Irradiation, Whole Body Irradiation, Whole-Body Irradiation
Undergo total-body irradiation
TreosulfanDrug
Also called 1,2,3, 4-Butanetetrol, 1,4-dimethanesulfonate, [R-(R*,S*)]-, Dihydroxybusulfan, Ovastat, Treosulphan
Given IV
Bone Marrow AspirationProcedure or surgery
Undergo bone marrow aspiration
Bone Marrow BiopsyProcedure or surgery
Undergo bone marrow biopsy
Echocardiography TestProcedure or surgery
Also called EC
Undergo echocardiography
Biospecimen CollectionProcedure or surgery
Undergo blood sample collection
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, CT, CT Scan
Undergo CT or PET/CT
Positron Emission TomographyProcedure or surgery
Also called PET, PET scan
Undergo PET/CT
| Study group | Role | What they receive |
|---|---|---|
| Arm A (high dose treosulfan) | Experimental | 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. Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Cyclosporine; Biological: Filgrastim; Drug: Fludarabine; Drug: Mycophenolate Mofetil; Drug: Mycophenolate Sodium; Radiation: Total-Body Irradiation; Drug: Treosulfan; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Echocardiography Test; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Positron Emission Tomography |
| Arm B (low dose treosulfan) | Experimental | 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. Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Cyclosporine; Biological: Filgrastim; Drug: Fludarabine; Drug: Mycophenolate Mofetil; Drug: Mycophenolate Sodium; Radiation: Total-Body Irradiation; Drug: Treosulfan; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Echocardiography Test; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Positron Emission Tomography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Graft failure/rejection
The analysis for graft failure will be conducted among all patients as well as separately among patients by Arm A versus Arm B.
Measured: Up to 2 years post-transplant
Secondary outcomes (8)
Overall survival
Measured: At 1 and 2 years post-transplant
Progression free survival
Defined as the probability of being alive without sign of disease relapse or progression. Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
Measured: At 1 year post-transplant
Non-relapse mortality
Defined as death from any cause without sign of disease progression or relapse. Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
Measured: At day 100 and 1 year post-transplant
Relapse
Measured: At 1 and 2 years post-treatment
Acute graft versus host disease
Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
Measured: Up to 2 years post-transplant
Chronic graft versus host disease
Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
Measured: Up to 2 years post-transplant
Clinically significant infections
Clinically significant infections include infections that have a significant impact on patient's clinical recovery, for instance infections that require in-patient hospitalization or prolongs existing hospitalization. Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
Measured: Up to 2 years post-transplant
Platelet engraftment
Defined as the first of three consecutive days with platelet count >= 20,000/uL on the peripheral blood, without platelet transfusion in the previous seven days. Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
Measured: At day 100 post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2019
- Study start25 Jan 2021
- Primary completion15 Apr 2027 (estimated)
- Study completion12 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- medac GmbH
- Responsible party
- Sponsor
- Investigators
- Phuong Vo, MD, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04195633
- Sponsor's protocol ID
- RG1005742
- Other IDs
- NCI-2019-07697, 10343
- Status last verified
- May 2026
- First submitted
- 10 Dec 2019
- Last updated
- 29 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No