search
Back to results

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

Primary Purpose

Acute Leukemia, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Hematopoietic Stem Cell Transplantation
Cyclophosphamide
Cyclosporine
Filgrastim
Fludarabine
Mycophenolate Mofetil
Mycophenolate Sodium
Total-Body Irradiation
Treosulfan
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Leukemia

Eligibility Criteria

6 Months - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Fred Hutch/University of Washington Cancer ConsortiumRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A (high dose treosulfan)

Arm B (low dose treosulfan)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall survival
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.
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.
Cumulative incidence of relapse
Acute graft versus host disease
Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
Chronic graft versus host disease
Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
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.
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.

Full Information

First Posted
December 10, 2019
Last Updated
May 12, 2023
Sponsor
Fred Hutchinson Cancer Center
Collaborators
medac GmbH
search

1. Study Identification

Unique Protocol Identification Number
NCT04195633
Brief Title
Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Total-Body Irradiation for the Treatment of Hematological Malignancies
Official Title
Hematopoietic Stem Cell Transplantation From Haploidentical Donors in Patients With Hematological Malignancies Using a Treosulfan-Based Preparative Regimen
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 25, 2021 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
medac GmbH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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. 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. After completion of transplant, patients are followed up at 28, 56, 84, 365, and 730 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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 Chronic Lymphocytic Leukemia, Refractory Follicular Lymphoma, Refractory Marginal Zone Lymphoma, Refractory Small Lymphocytic Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A (high dose treosulfan)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm B (low dose treosulfan)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic
Intervention Description
Undergo allogeneic hematopoietic stem cell transplantation
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
(-)-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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Cyclosporine
Other Intervention Name(s)
27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Cyclosporine Modified, Gengraf, Neoral, OL 27-400, Sandimmune, SangCya
Intervention Description
Given IV or PO
Intervention Type
Biological
Intervention Name(s)
Filgrastim
Other Intervention Name(s)
G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim, Filgrastim-aafi, Nivestym
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fluradosa
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
Cellcept, MMF
Intervention Description
Given IV or PO
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Sodium
Other Intervention Name(s)
ERL 080, ERL 080A, Socium Mycophenolate
Intervention Description
Given PO
Intervention Type
Radiation
Intervention Name(s)
Total-Body Irradiation
Other Intervention Name(s)
TBI, Total Body Irradiation, Whole Body Irradiation, Whole-Body Irradiation, SCT_TBI
Intervention Description
Undergo total-body irradiation
Intervention Type
Drug
Intervention Name(s)
Treosulfan
Other Intervention Name(s)
1,2,3, 4-Butanetetrol, 1,4-dimethanesulfonate, [R-(R*,S*)]-, Dihydroxybusulfan, Ovastat, Treosulphan, Tresulfon
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Graft failure/rejection
Description
The analysis for graft failure will be conducted among all patients as well as separately among patients by Arm A versus Arm B.
Time Frame
Up to 2 years post-transplant
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
At 1- and 2-years post-transplant
Title
Progression free survival
Description
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.
Time Frame
At 1 year post-transplant
Title
Non-relapse mortality
Description
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.
Time Frame
At day 100 and 1 year post-transplant
Title
Cumulative incidence of relapse
Time Frame
At 1- and 2-years post-treatment
Title
Acute graft versus host disease
Description
Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
Time Frame
Up to 2 years post-transplant
Title
Chronic graft versus host disease
Description
Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
Time Frame
Up to 2 years post-transplant
Title
Clinically significant infections
Description
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.
Time Frame
Up to 2 years post-transplant
Title
Platelet engraftment
Description
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.
Time Frame
At day 100 post-transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Filippo Milano
Phone
206.667.5925
Email
fmilano@fredhutch.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Filippo Milano
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Filippo Milano
Phone
206-667-5925
Email
fmilano@fredhutch.org
First Name & Middle Initial & Last Name & Degree
Filippo Milano

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs