Graft Versus Host Disease-Reduction Strategies for Donor Blood Stem Cell Transplant Patients With Acute Leukemia

  • End date
    Aug 1, 2024
  • participants needed
  • sponsor
    Fred Hutchinson Cancer Research Center
Updated on 8 May 2021
stem cell transplantation
graft versus host disease
myeloid leukemia
lymphoid leukemia
total body irradiation
acute leukemia
white blood cell count
lymphoblastic lymphoma
cell transplantation
lymphocytic leukemia
antithymocyte globulin
blast cells
blood cell count


This phase II trial investigates three strategies and how well they work for the reduction of graft versus host disease in patients with acute leukemia in remission. Giving chemotherapy and total-body irradiation before a donor peripheral blood 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.



Patients are randomized to 1 of 3 arms.

ARM A: Patients undergo total-body irradiation (TBI) twice daily (BID) on days -10 to -7, and receive thiotepa intravenously (IV) over 3 hours on days -6 and -5, fludarabine IV over 30 minutes on days -6 to -2, tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day -1, CD34+ enriched CD45RA-depleted donor T-lymphocytes IV on day 0, and methotrexate IV on days 1, 3, 6, and 11. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid).

ARM C: Patients undergo TBI BID on days -4 to -2 or -3 to -1, and receive PBSC IV on day 0. Patients also receive cyclophosphamide IV over 1 hour on days 3 and 4, and tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day 5. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid).

ARM D: Patients undergo TBI BID on days -6 to -4, and receive cyclophosphamide IV over 1 hour on days -3 to -2, tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day -1, PBSC IV on day 0, and methotrexate IV on days 1, 3, 6, and 11. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid).

After completion of study treatment, patients are followed up at days 7, 14, 21, 28, 56, 80, 180, and 270 and at 1, 1.5, and 2 years.

Condition childhood ALL, Hematologic Malignancy, organ donor, Acute myeloid leukemia, Acute biphenotypic leukemia, Acute Myelogenous Leukemia (AML), Acute Myeloid Leukemia in Remission, Blasts Under 5 Percent of Bone Marrow Nucleated Cells, Acute Leukemia, Acute Undifferentiated Leukemia, Mixed Phenotype Acute Leukemia, Acute Lymphoblastic Leukemia in Remission, Acute Leukemia of Ambiguous Lineage, Blastic Plasmacytoid Dendritic Cell Neoplasm, Lymphocytic Leukemia, Acute, Allogeneic Hematopoietic Stem Cell Transplantation Recipient, Blood Cancer, Hematologic Cancer, Hematologic Neoplasms, acute lymphoblastic leukemia, hematopoietic and lymphoid cell neoplasm, leukemia, acute lymphoblastic, lymphoblastic lymphoma, acute leukemias, biphenotypic acute leukemia, acute lymphoid leukaemia, acute lymphocytic leukemia, acute lymphoblastic leukemia (all), acute myelogenous leukemia, anll, acute myeloblastic leukemia, hematopoietic malignancy
Treatment anti-thymocyte globulin, cyclophosphamide, cyclosporine, fludarabine phosphate, methotrexate, Fludarabine, Tacrolimus, Total-Body Irradiation, Sirolimus, thiotepa, Peripheral blood stem cell, Allogeneic CD34+-enriched and CD45RA-depleted PBSCs, Allogeneic CD34-positive Enriched Peripheral Blood Stem Cells
Clinical Study IdentifierNCT03970096
SponsorFred Hutchinson Cancer Research Center
Last Modified on8 May 2021


Yes No Not Sure

Inclusion Criteria

Patients who are considered appropriate candidates for myeloablative, TBI-containing allogeneic hematopoietic stem cell transplantation and have one of the following
Acute lymphocytic leukemia (ALL) in first or subsequent morphological remission (< 5% marrow blasts by morphology)
Acute myeloid leukemia (AML) in first or subsequent morphological remission (< 5% marrow blasts by morphology)
Other acute leukemia or related neoplasm (including but not limited to 'mixed phenotype' 'biphenotypic', 'acute undifferentiated' or 'ambiguous lineage' acute leukemia, blastic plasmacytoid dendritic cell neoplasm or lymphoblastic lymphoma) in first or subsequent morphological remission (< 5% marrow blasts by morphology)
Patient age 1 -50 years old (inclusive) at the time of informed consent
Patient with an HLA-matched (HLA-A, B, C, DRB1, and DQB1 matched) related or unrelated donor capable of donating PBSC
Recipient informed consent/assent and/or legal guardian permission must be obtained
DONOR: HLA-matched related and unrelated donors (HLA-A, B, C, DRB1 and DQB1 matched based on high-resolution typing)
DONOR: >= 18 years old
DONOR: Willing to donate PBSC
DONOR: Matched related donors
Must give informed consent using the related donor informed consent form
DONOR: Matched unrelated donors
Must meet institutional donor eligibility criteria or be ineligible with statement that the donor is a first or second degree relative (exception 21 Code of Federal Regulations [CFR] 1271.65(b)(i))
Must consent according to the applicable National Marrow Donor Program (NMDP) donor regulatory requirements
Must meet eligibility criteria as defined by the NMDP or be ineligible with statement of urgent medical need (exception 21 CFR 1271.65(b)(iii))

Exclusion Criteria

Patients with central nervous system (CNS) involvement refractory to intrathecal chemotherapy and/or standard cranial-spinal radiation. A patient may have a history of CNS disease. However, any CNS disease must be cleared by the end of the pre-conditioning evaluation time frame. If CNS disease is identified on cerebrospinal fluid (CSF) evaluation within 30 days of the start of the preparative regimen a repeat CSF evaluation must be performed and show no evidence of disease in order for the patient to be eligible for the protocol
Patients on other experimental protocols for prevention of GVHD
Patient weight
Patients with HLA-matched related donors will be excluded if they weigh >= 100 kg
Patients with HLA-matched unrelated donors will be excluded if they weigh >= 100 kg and must be discussed with the Fred Hutch protocol principal investigator (PI) if they weigh >= 80 kg
Patients who are positive for human immunodeficiency virus (HIV)-1, HIV-2, human T-cell lymphotropic virus (HTLV)1 or HTLV2
Patients with uncontrolled infections for whom myeloablative HCT is considered contraindicated by the consulting infectious disease physician; i.e. patients with active infections require infectious disease consultation and documentation by the infectious disease team that myeloablative HCT is not considered to be contraindicated. Upper respiratory tract infection is not considered to represent an uncontrolled infection in this context
Patients with organ dysfunction, including
Renal insufficiency (creatinine > 1.5 mg/dl) at the time of evaluation for the protocol. Patients with a known history of creatinine > 1.5 mg/dl or a current serum creatinine above the normal range for age must have a current creatinine clearance of > 60 ml/min/1.73 m^2 (measured by 24-hr urine specimen or nuclear glomerular filtration rate [GFR])
Left ventricular ejection fraction < 45%
Carbon monoxide diffusing capability (DLCO) corrected < 60%. Patients who are unable to perform pulmonary function tests (for example, due to young age and/or developmental status) will be excluded if the oxygen (O2) saturation is < 92% on room air
Liver function abnormality. Patients who have liver function test (LFT)s (specifically, total bilirubin, aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) >= twice the upper limit of normal should be evaluated by a gastrointestinal (GI) physician unless there is a clear precipitating factor (such as an azole, MTX, trimethoprim-sulfamethoxazole, or another drug). If the GI physician considers that HCT on the protocol is contraindicated, that patient will be excluded from the protocol. Patients with Gilbert's syndrome and no other known liver function abnormality or with reversible drug-related transaminitis do not necessarily require GI consultation and may be included on the protocol
Patients who have received previous myeloablative allogeneic or autologous transplantation
Patients with a life expectancy < 12 months from co-existing disease other than the leukemia
Patients who are pregnant or breast-feeding
Patients of childbearing age who are presumed to be fertile and are unwilling to use an effective birth control method or refrain from sexual intercourse during and for 12 months post-HCT
Patients with any other significant medical conditions that would make them unsuitable for transplantation, as determined by the PI
Patients who have received checkpoint inhibitors within three months of transplantation unless an exception is made by the PI
DONOR: Donors who are HIV-1, HIV-2, HTLV-1, HTLV-2 seropositive or with active hepatitis B or hepatitis C virus infection. Test must be performed using Food and Drug Administration (FDA) licensed, cleared, and approved test kits (serological and/or nucleic acid amplification test [NAT] and/or other approved testing) in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
Patients with a known hypersensitivity to tacrolimus, MTX or thymoglobulin
DONOR: Unrelated donors donating outside of the United States of America (USA)
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