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  • Cancer Type: Malignant Hematology
  • Study Type: Treatment
  • NCT#: NCT03970096
  • Phase: Phase II
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  • Overview

    Study Title:

    A Phase II Randomized Controlled Trial Comparing GVHD-Reduction Strategies for Allogeneic Peripheral Blood Transplantation (PBSCT) for Patients with Acute Leukemia or Myelodysplastic Syndrome: Selective Depletion of CD45RA+ Naïve T Cells (TND) vs. Post-Transplantation Cyclophosphamide (PTCy)


    This phase II trial investigates two strategies and how well they work for the reduction of graft versus host disease in patients with acute leukemia or MDS 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.


    Primary Objective: To estimate the rate of clinically significant GVHD-free* relapse-free survival (GRFS) at 2 years in patients treated with PBSCT and TnD, tacrolimus, and MTX (Arm A); PTCy and tacrolimus (Arm C); or tacrolimus and MTX (Arm D), and to determine whether GRFS may be higher in patients who receive treatment on Arms A or C compared to Arm D. GRFS is defined as free of a history of post-HCT relapse, grade III-IV acute GVHD, or cGVHD* (*NIH-criteria, moderate and severe, requiring systemic IS) at 2 years post-transplantation. Secondary Objectives: In patients transplanted with PBSCT on Arms A, C, or D of the protocol to estimate: The rate of overall survival (OS). The rate of relapse. The proportion of patients alive and off prednisone (or equivalent systemic corticosteroid) for treatment of GVHD at 3, 6, 9, 12, 15, 18, 21, 24 months post HCT. The rate of cGVHD (meeting NIH-criteria, requiring systemic IS) and the rate of cGVHD requiring IS of specific grades (a. mild; b. moderate; c. severe)

  • Treatments


    Chemotherapy (NOS); Radiotherapy; Therapy (NOS)


    FK506 (Tacrolimus); MESNA (); PBSC (); Tacrolimus (); Thiotepa (Thioplex); busulfan (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate); methotrexate ()

  • Inclusion Criteria

      Inclusion Criteria:
    • Patients who are considered appropriate candidates for myeloablative, TBI-containing allogeneic hematopoietic stem cell transplantation and have one of the following diagnoses: (1) Acute lymphocytic leukemia (ALL) in first or subsequent morphological remission (2) Acute myeloid leukemia (AML) in first or subsequent morphological remission (3) 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, lymphoblastic lymphoma, Burkitt leukemia/lymphoma, mast cell leukemia, or chronic myeloid leukemia (CML) with blast crisis) in first or subsequent morphological remission (4) Myelodysplastic syndrome (MDS) with a history of excess blasts and a history of receiving cytoreductive therapy (including but not limited to BCL-2 inhibitors or cytotoxic chemotherapy) within the past 3 months.
    • Patient age 1-60 years old (inclusive) at the time of informed consent. Patients aged 1-50 years old (inclusive) are eligible for TBI-based conditioning regimens. Patients aged 1-60 years old (inclusive) are eligible for busulfan-based conditioning regimens (with or without TBI 4 Gy)
    • 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 or older.
    • DONOR: Willing to donate PBSC.
    • DONOR: Matched related donors collecting through the same institutional site as the patient: Must give informed consent using the related donor informed consent form. 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)).
    • DONOR: Matched unrelated donors and related donors collecting through the National Marrow Donor Program (NMDP) : Must consent according to the applicable (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)). Must be vaccinated against COVID19. 'COVID vaccinated' is as defined by the NMDP and number of required doses may vary according to vaccine manufacturer and evolving guidelines.
    • Other criteria may apply
  • Exclusion Criteria

      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 >= 90 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, as outlined in protocol.
    • Patients who have received previous myeloablative allogeneic or autologous transplantation.
    • Patients with a life expectancy > 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 with a known hypersensitivity to tacrolimus or MTX
    • 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.
    • Unrelated donors donating outside of the USA.
    • Other exclusions may apply

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