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

  • STATUS
    Recruiting
  • End date
    Dec 31, 2025
  • participants needed
    60
  • sponsor
    Fred Hutchinson Cancer Research Center
Updated on 29 March 2021

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.

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.

Details
Condition Bone marrow disorder, childhood ALL, Hodgkin's Disease, Hematologic Malignancy, Chronic myelomonocytic leukemia, Juvenile Myelomonocytic Leukemia, Lymphoma, Preleukemia, Waldenstrom's Macroglobulinemia, Acute myeloid leukemia, Mantle cell lymphoma, anaplastic large cell lymphoma, Lymphoma, Burkitt's Lymphoma, B-Cell Lymphoma, T-Cell Lymphoma, MYELODYSPLASTIC SYNDROME, Chronic myeloid leukemia, Prolymphocytic Leukemia, Non-Hodgkin's Lymphoma, Lymphoma, B-Cell, Myelodysplastic Syndromes (MDS), Acute Myelogenous Leukemia (AML), Refractory Chronic Lymphocytic Leukemia, Refractory Small Lymphocytic Lymphoma, Acute Leukemia, Mixed Phenotype Acute Leukemia, Refractory Follicular Lymphoma, Lymphocytic Leukemia, Acute, Adult Diffuse Large Cell Lymphoma, Refractory Marginal Zone Lymphoma, Blood Cancer, Hematologic Cancer, Hematologic Neoplasms, Waldenstrom Macroglobulinemia, Chronic Lymphocytic Leukemia Refractory, acute lymphoblastic leukemia, hematopoietic and lymphoid cell neoplasm, leukemia, acute lymphoblastic, lymphoblastic lymphoma, myelodysplastic syndromes, burkitt lymphoma, myelodysplastic syndrome (mds), hodgkin, hodgkin's lymphomas, hodgkin lymphomas, hodgkins lymphoma, hodgkin's lymphoma, acute leukemias, acute lymphoid leukaemia, acute lymphocytic leukemia, acute lymphoblastic leukemia (all), acute myelogenous leukemia, anll, acute myeloblastic leukemia, hematopoietic malignancy, chronic myelomonocytic leukaemia, cmml
Treatment cyclophosphamide, cyclosporine, mycophenolate mofetil, filgrastim, allogeneic hematopoietic stem cell transplantation, Fludarabine, Total-Body Irradiation, treosulfan, Mycophenolate Sodium
Clinical Study IdentifierNCT04195633
SponsorFred Hutchinson Cancer Research Center
Last Modified on29 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 1 yrs?
Gender: Male or Female
Do you have any of these conditions: burkitt lymphoma or Hematologic Malignancy or Adult Diffuse Large Cell Lymphoma or Refractory Small Lymphocytic Lymphoma or Acute Myelogenous Leukemia...?
Do you have any of these conditions: acute lymphoid leukaemia or Acute myeloid leukemia or Acute Leukemia or Chronic myeloid leukemia or Refractory Follicular Lymphoma or Waldenstrom Macr...?
Do you have any of these conditions: acute leukemias or myelodysplastic syndromes or Hematologic Malignancy or Lymphoma, B-Cell or Mantle cell lymphoma or cmml or Preleukemia or MYELODYSP...?
Do you have any of these conditions: acute lymphoblastic leukemia (all) or Refractory Small Lymphocytic Lymphoma or Hematologic Cancer or hodgkin lymphomas or Lymphoma or myelodysplastic ...?
Do you have any of these conditions: hodgkin or Lymphoma, B-Cell or Non-Hodgkin's Lymphoma or myelodysplastic syndromes or Adult Diffuse Large Cell Lymphoma or burkitt lymphoma or Hematol...?
Do you have any of these conditions: Waldenstrom's Macroglobulinemia or acute myelogenous leukemia or hematopoietic and lymphoid cell neoplasm or B-Cell Lymphoma or Chronic myeloid leukem...?
Do you have any of these conditions: anaplastic large cell lymphoma or Acute Leukemia or Prolymphocytic Leukemia or lymphoblastic lymphoma or acute myeloblastic leukemia or cmml or Juveni...?
Do you have any of these conditions: Burkitt's Lymphoma or hodgkin or Myelodysplastic Syndromes (MDS) or Acute Leukemia or hodgkin's lymphomas or Chronic Lymphocytic Leukemia Refractory o...?
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 no earlier than one month before conditioning regimen start. 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
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 at the Seattle Cancer Care Alliance (SCCA)
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, and in case of positivity, the donor will be excluded
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