- ICH GCP
- US Clinical Trials Registry
- Clinical Trial 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
Study Overview
Status
Conditions
- Acute Myeloid Leukemia
- Hodgkin Lymphoma
- Chronic Myelomonocytic Leukemia
- Burkitt Lymphoma
- Acute Lymphoblastic Leukemia
- Lymphoblastic Lymphoma
- Mantle Cell Lymphoma
- Lymphoplasmacytic Lymphoma
- Anaplastic Large Cell Lymphoma
- Acute Leukemia
- Myelodysplastic Syndrome
- Prolymphocytic Leukemia
- Refractory Chronic Lymphocytic Leukemia
- Refractory Small Lymphocytic Lymphoma
- Refractory Follicular Lymphoma
- Refractory Marginal Zone Lymphoma
- Mixed Phenotype Acute Leukemia
- Adult Diffuse Large Cell Lymphoma
- Chronic Myeloid Leukemia, BCR-ABL1 Positive
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Filippo Milano
- Phone Number: 206.667.5925
- Email: fmilano@fredhutch.org
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Recruiting
- Fred Hutch/University of Washington Cancer Consortium
-
Contact:
- Filippo Milano
- Phone Number: 206-667-5925
- Email: fmilano@fredhutch.org
-
Principal Investigator:
- Filippo Milano
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV or PO
Other Names:
Given IV or PO
Other Names:
Undergo allogeneic hematopoietic stem cell transplantation
Other Names:
Given PO
Other Names:
Undergo total-body irradiation
Other Names:
|
Experimental: 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.
|
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV or PO
Other Names:
Given IV or PO
Other Names:
Undergo allogeneic hematopoietic stem cell transplantation
Other Names:
Given PO
Other Names:
Undergo total-body irradiation
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Graft failure/rejection
Time Frame: Up to 2 years post-transplant
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: At 1- and 2-years post-transplant
|
At 1- and 2-years post-transplant
|
|
Progression free survival
Time Frame: At 1 year post-transplant
|
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.
|
At 1 year post-transplant
|
Non-relapse mortality
Time Frame: At day 100 and 1 year post-transplant
|
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.
|
At day 100 and 1 year post-transplant
|
Cumulative incidence of relapse
Time Frame: At 1- and 2-years post-treatment
|
At 1- and 2-years post-treatment
|
|
Acute graft versus host disease
Time Frame: Up to 2 years post-transplant
|
Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
|
Up to 2 years post-transplant
|
Chronic graft versus host disease
Time Frame: Up to 2 years post-transplant
|
Will be summarized using Kaplan-Meier and cumulative incidence estimates, as appropriate.
|
Up to 2 years post-transplant
|
Clinically significant infections
Time Frame: Up to 2 years post-transplant
|
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.
|
Up to 2 years post-transplant
|
Platelet engraftment
Time Frame: At day 100 post-transplant
|
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.
|
At day 100 post-transplant
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Filippo Milano, Fred Hutch/University of Washington Cancer Consortium
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Virus Diseases
- Infections
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplasms by Site
- Disease Attributes
- Bone Marrow Diseases
- Hematologic Diseases
- Hemorrhagic Disorders
- Myeloproliferative Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- DNA Virus Infections
- Tumor Virus Infections
- Neoplasms, Plasma Cell
- Myelodysplastic-Myeloproliferative Diseases
- Leukemia, Lymphoid
- Epstein-Barr Virus Infections
- Herpesviridae Infections
- Leukemia, B-Cell
- Lymphoma, B-Cell
- Lymphoma, T-Cell
- Lymphoma
- Lymphoma, Large B-Cell, Diffuse
- Myelodysplastic Syndromes
- Hematologic Neoplasms
- Leukemia
- Leukemia, Myeloid
- Lymphoma, Non-Hodgkin
- Leukemia, Myelomonocytic, Chronic
- Leukemia, Myelomonocytic, Juvenile
- Burkitt Lymphoma
- Lymphoma, Mantle-Cell
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Waldenstrom Macroglobulinemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Acute Disease
- Lymphoma, Large-Cell, Anaplastic
- Leukemia, Prolymphocytic
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Dermatologic Agents
- Anti-Bacterial Agents
- Adjuvants, Immunologic
- Antibiotics, Antineoplastic
- Antifungal Agents
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Cyclophosphamide
- Lenograstim
- Fludarabine
- Mycophenolic Acid
- Busulfan
- Cyclosporine
- Cyclosporins
- Treosulfan
Other Study ID Numbers
- RG1005742
- NCI-2019-07697 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- 10343 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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