Recruitment

Recruitment Status
Recruiting

Inclusion Criteria

Subjects must be >= 6 months old
Minor ABO incompatibility
Total bilirubin < 2 x upper limit of normal (ULN) unless felt to be related to Gilbert's disease or hemolysis
...
Subjects must be >= 6 months old
Minor ABO incompatibility
Total bilirubin < 2 x upper limit of normal (ULN) unless felt to be related to Gilbert's disease or hemolysis
Major ABO incompatibility
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)
If recent mold infection, e.g., aspergillus, must be cleared by infectious disease to proceed
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
Red blood cell (RBC) cross match compatible
DONOR: Weight >= 40 Kg
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)
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
For cytomegalovirus (CMV) seronegative recipients, a CMV seronegative donor
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
Lansky score >= 50 (for children)
Karnofsky >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1 (for adults)
Alkaline phosphatase =< 5 x ULN
Myelodysplastic syndromes (MDS)
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
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
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
DONOR: Age >= 12 years
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
All adults with a creatinine > 1.2 or a history of renal dysfunction must have estimated creatinine clearance > 40 ml/min
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
Chronic myelomonocytic leukemia (CMML)
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
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
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
Adequate cardiac function defined as absence of decompensated congestive heart failure or uncontrolled arrhythmia AND left ventricular ejection fraction >= 40% or shortening fraction > 22%
DLCO corrected between 60% - 69% mm Hg and partial pressure of oxygen (pO2) >= 70 mm Hg
Diffusion capacity of the lung for carbon monoxide (DLCO) corrected > 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
Written and signed informed consent

Exclusion Criteria

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)
...
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 will be reviewed by the principal investigator and considered for desensitization treatment.
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

Summary

Conditions
  • Acute Lymphoblastic Leukemia
  • Acute Leukemia
  • Refractory Chronic Lymphocytic Leukemia
  • Myelodysplastic Syndrome
  • Prolymphocytic Leukemia
  • Acute Myeloid Leukemia
  • Refractory Marginal Zone Lymphoma
  • Adult Diffuse Large Cell Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Burkitt Lymphoma
  • Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Chronic Myelomonocytic Leukemia
  • Refractory Follicular Lymphoma
  • Hodgkin Lymphoma
  • Mantle Cell Lymphoma
  • Refractory Small Lymphocytic Lymphoma
  • Lymphoblastic Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mixed Phenotype Acute Leukemia
Type
Interventional
Phase
Phase 2
Design
  • Allocation: Non-Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 6 years and 125 years
Gender
Both males and females

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 hematopoi...

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.

Inclusion Criteria

Subjects must be >= 6 months old
Minor ABO incompatibility
Total bilirubin < 2 x upper limit of normal (ULN) unless felt to be related to Gilbert's disease or hemolysis
...
Subjects must be >= 6 months old
Minor ABO incompatibility
Total bilirubin < 2 x upper limit of normal (ULN) unless felt to be related to Gilbert's disease or hemolysis
Major ABO incompatibility
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)
If recent mold infection, e.g., aspergillus, must be cleared by infectious disease to proceed
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
Red blood cell (RBC) cross match compatible
DONOR: Weight >= 40 Kg
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)
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
For cytomegalovirus (CMV) seronegative recipients, a CMV seronegative donor
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
Lansky score >= 50 (for children)
Karnofsky >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1 (for adults)
Alkaline phosphatase =< 5 x ULN
Myelodysplastic syndromes (MDS)
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
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
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
DONOR: Age >= 12 years
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
All adults with a creatinine > 1.2 or a history of renal dysfunction must have estimated creatinine clearance > 40 ml/min
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
Chronic myelomonocytic leukemia (CMML)
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
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
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
Adequate cardiac function defined as absence of decompensated congestive heart failure or uncontrolled arrhythmia AND left ventricular ejection fraction >= 40% or shortening fraction > 22%
DLCO corrected between 60% - 69% mm Hg and partial pressure of oxygen (pO2) >= 70 mm Hg
Diffusion capacity of the lung for carbon monoxide (DLCO) corrected > 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
Written and signed informed consent

Exclusion Criteria

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)
...
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 will be reviewed by the principal investigator and considered for desensitization treatment.
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

Tracking Information

NCT #
NCT04195633
Collaborators
medac GmbH
Investigators
Filippo Milano Fred Hutch/University of Washington Cancer Consortium