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

NCT04195633 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1005742NCI-2019-0769710343
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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; 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 Follicular Lymphoma; Refractory Marginal Zone Lymphoma; Refractory Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 2 years post-transplant

Secondary Outcomes (8)

• Overall survival

  At 1 and 2 years post-transplant

• Progression free survival

  At 1 year post-transplant

• Non-relapse mortality

  At day 100 and 1 year post-transplant

• Relapse

  At 1 and 2 years post-treatment

• Acute graft versus host disease

  Up to 2 years post-transplant

Study Arms (2)

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.

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.

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

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic hematopoietic stem cell transplantation

Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Arm A (high dose treosulfan); Arm B (low dose treosulfan)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Arm A (high dose treosulfan); Arm B (low dose treosulfan)

Cyclosporine DRUG

Given IV or PO

Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Cyclosporine Modified, Gengraf, Neoral, OL 27-400, Sandimmune, SangCya

Arm A (high dose treosulfan); Arm B (low dose treosulfan)

Filgrastim BIOLOGICAL

Given IV

Also known as: G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim, Filgrastim-aafi, Nivestym

Arm A (high dose treosulfan); Arm B (low dose treosulfan)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Arm A (high dose treosulfan); Arm B (low dose treosulfan)

Mycophenolate Mofetil DRUG

Given IV or PO

Also known as: Cellcept, MMF

Arm A (high dose treosulfan); Arm B (low dose treosulfan)

Mycophenolate Sodium DRUG

Given PO

Also known as: ERL 080, ERL 080A, Socium Mycophenolate

Arm A (high dose treosulfan); Arm B (low dose treosulfan)

Total-Body Irradiation RADIATION

Undergo total-body irradiation

Also known as: TBI, Total Body Irradiation, Whole Body Irradiation, Whole-Body Irradiation, SCT_TBI

Arm A (high dose treosulfan); Arm B (low dose treosulfan)

Treosulfan DRUG

Given IV

Also known as: 1,2,3, 4-Butanetetrol, 1,4-dimethanesulfonate, [R-(R*,S*)]-, Dihydroxybusulfan, Ovastat, Treosulphan, Tresulfon, Grafapex

Arm A (high dose treosulfan); Arm B (low dose treosulfan)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Arm A (high dose treosulfan); Arm B (low dose treosulfan)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Arm A (high dose treosulfan); Arm B (low dose treosulfan)

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC

Arm A (high dose treosulfan); Arm B (low dose treosulfan)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Arm A (high dose treosulfan); Arm B (low dose treosulfan)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, CT, CT Scan, Computerized Axial Tomography

Arm A (high dose treosulfan); Arm B (low dose treosulfan)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: PET, PET scan

Arm A (high dose treosulfan); Arm B (low dose treosulfan)

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• medac GmbH: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

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; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Mantle-Cell; Leukemia, Biphenotypic, Acute; Myelodysplastic Syndromes; Leukemia, Prolymphocytic; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular

Interventions

Stem Cell Transplantation; Cyclophosphamide; Cyclosporine; Cyclosporins; Filgrastim; Granulocyte Colony-Stimulating Factor; fludarabine; Mycophenolic Acid; Whole-Body Irradiation; treosulfan; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myelodysplastic-Myeloproliferative Diseases; Leukemia, B-Cell

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Radiotherapy; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Filippo Milano

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Filippo Milano

CONTACT

206.667.5925; fmilano@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: December 12, 2019
• Study Start: January 25, 2021
• Primary Completion (Estimated): April 15, 2027
• Study Completion (Estimated): March 12, 2029
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)