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Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02220985
Recruitment Status : Active, not recruiting
First Posted : August 20, 2014
Last Update Posted : December 24, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

Tracking Information
First Submitted Date  ICMJE August 18, 2014
First Posted Date  ICMJE August 20, 2014
Last Update Posted Date December 24, 2020
Actual Study Start Date  ICMJE February 3, 2015
Estimated Primary Completion Date April 1, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 31, 2018)
  • Occurrence of chronic graft-versus-host disease (GHVD), defined operationally as the occurrence of compatible symptoms meeting National Institutes of Health criteria and requiring systemic pharmacological immunosuppression [ Time Frame: Up to 5 years ]
    Match related donor (MRD)-high intensity (Arm A), MRD-lower intensity (Arm B), match unrelated donor (MUD)-high intensity (Arm C) and MUD-lower intensity (Arm D) cohorts will be analyzed separately.
  • Use of additional immune suppressive agents other than first line therapy (prednisone and tacrolimus/cyclosporine) [ Time Frame: Up to 5 years ]
  • Time to completion of prednisone [ Time Frame: Up to 5 years ]
  • Time to completion of all immunosuppression [ Time Frame: Up to 5 years ]
  • Requirement of immunosuppression after transplant [ Time Frame: At 2 years after transplant ]
  • Presence of acute graft-versus-host disease (GVHD) grades II-IV [ Time Frame: Up to day 100 ]
    Defined operationally as the occurrence of compatible symptoms or signs in the skin, gastrointestinal tract, or liver.
  • Requirement for secondary systemic therapy for acute graft-versus-host disease (GVHD) management [ Time Frame: Up to day 100 ]
  • Graft failure [ Time Frame: Up to day 28 ]
    Defined operationally as failure to reach an absolute neutrophil count (ANC) of > 500/ul for 3 consecutive days by day 28 or irreversible decrease in ANC to < 100 after an established donor graft.
Original Primary Outcome Measures  ICMJE
 (submitted: August 18, 2014)
  • Occurrence of chronic GHVD, defined operationally as the occurrence of compatible symptoms meeting National Institutes of Health criteria and requiring systemic pharmacological immunosuppression [ Time Frame: Up to 5 years ]
  • Use of additional immune suppressive agents other than first line therapy (prednisone and tacrolimus/cyclosporine) [ Time Frame: Up to 5 years ]
  • Time to completion of prednisone [ Time Frame: Up to 5 years ]
  • Time to completion of all immunosuppression [ Time Frame: Up to 5 years ]
  • Requirement of immunosuppression after transplant [ Time Frame: At 2 years after transplant ]
  • Presence of acute GVHD grades II-IV, defined operationally as the occurrence of compatible symptoms or signs in the skin, gastrointestinal tract, or liver prior to day +100 [ Time Frame: Up to day 100 ]
  • Requirement for secondary systemic therapy for acute GVHD management [ Time Frame: Up to day 100 ]
  • Graft failure, defined operationally as failure to reach an absolute neutrophil count (ANC) of > 500/ul for 3 consecutive days by day 28 or irreversible decrease in ANC to < 100 after an established donor graft [ Time Frame: Up to day 28 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2018)
  • Time to absolute neutrophil count (ANC) of > 500/uL on the first of three consecutive days [ Time Frame: Up to 5 years ]
  • Time to absolute neutrophil count (ANC) of > 1,000/uL on the first of three consecutive test results [ Time Frame: Up to 5 years ]
  • Time to platelet count > 20,000/uL for 3 days without transfusion [ Time Frame: Up to 5 years ]
  • Time to platelet count > 50,000/uL for 3 days without transfusion [ Time Frame: Up to 5 years ]
  • Chimerism analysis [ Time Frame: Up to 360 days ]
    Will be analyzed from peripheral blood or marrow.
  • Relapse [ Time Frame: Up to 5 years ]
    Defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology.
  • Transplant related mortality [ Time Frame: Up to 5 years ]
    Defined as mortality in any patient for whom there has not been a diagnosis of relapse.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2014)
  • Time to ANC of > 500/uL on the first of three consecutive days [ Time Frame: Up to 5 years ]
  • Time to ANC of > 1,000/uL on the first of three consecutive test results [ Time Frame: Up to 5 years ]
  • Time to platelet count > 20,000/uL for 3 days without transfusion [ Time Frame: Up to 5 years ]
  • Time to platelet count > 50,000/uL for 3 days without transfusion [ Time Frame: Up to 5 years ]
  • Chimerism analysis [ Time Frame: Up to 360 days ]
  • Relapse, defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology [ Time Frame: Up to 5 years ]
  • Transplant related mortality, defined as mortality in any patient for whom there has not been a diagnosis of relapse [ Time Frame: Up to 5 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD
Official Title  ICMJE A Phase II Study Evaluating Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors for Prevention of GVHD
Brief Summary This phase II trial is for patients with acute lymphocytic leukemia, acute myeloid leukemia, myelodysplastic syndrome or chronic myeloid leukemia who have been referred for a peripheral blood stem cell transplantation to treat their cancer. In these transplants, chemotherapy and total-body radiotherapy ('conditioning') are used to kill residual leukemia cells and the patient's normal blood cells, especially immune cells that could reject the donor cells. Following the chemo/radiotherapy, blood stem cells from the donor are infused. These stem cells will grow and eventually replace the patient's original blood system, including red cells that carry oxygen to our tissues, platelets that stop bleeding from damaged vessels, and multiple types of immune-system white blood cells that fight infections. Mature donor immune cells, especially a type of immune cell called T lymphocytes (or T cells) are transferred along with these blood-forming stem cells. T cells are a major part of the curative power of transplantation because they can attack leukemia cells that have survived the chemo/radiation therapy and also help to fight infections after transplantation. However, donor T cells can also attack a patient's healthy tissues in an often-dangerous condition known as Graft-Versus-Host-Disease (GVHD). Drugs that suppress immune cells are used to decrease the severity of GVHD; however, they are incompletely effective and prolonged immunosuppression used to prevent and treat GVHD significantly increases the risk of serious infections. Removing all donor T cells from the transplant graft can prevent GVHD, but doing so also profoundly delays infection-fighting immune reconstitution and eliminates the possibility that donor immune cells will kill residual leukemia cells. Work in animal models found that depleting a type of T cell, called naïve T cells or T cells that have never responded to an infection, can diminish GVHD while at least in part preserving some of the benefits of donor T cells including resistance to infection and the ability to kill leukemia cells. This clinical trial studies how well the selective removal of naïve T cells works in preventing GVHD after peripheral blood stem cell transplants. This study will include patients conditioned with high or medium intensity chemo/radiotherapy who can receive donor grafts from related or unrelated donors.
Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the probability of developing chronic GHVD among patients who receive naive T cell (TN)-depleted peripheral blood stem cell transplant (PBSCT) in each of the following groups: a) Arm A: patients who receive TN-depleted peripheral blood stem cells (PBSC) from a human leukocyte antigens (HLA) matched related donor (MRD) following high-intensity myeloablative conditioning (total body irradiation [TBI] 1320 cGy, thiotepa, fludarabine phosphate [fludarabine]) and pharmacological immunosuppression with tacrolimus and methotrexate; b) Arm B: patients who receive TN-depleted PBSC from a MRD following lower-intensity myeloablative conditioning (TBI 400 cGy, thiotepa, fludarabine and cyclophosphamide) and pharmacological immunosuppression with tacrolimus and mycophenolate mofetil (MMF); c) Arm C: patients who receive TN-depleted PBSC from a HLA-matched unrelated donor (MUD) following high-intensity myeloablative conditioning (TBI 1320 cGy, thiotepa, fludarabine) and pharmacological immunosuppression with tacrolimus and methotrexate; d) Arm D: patients who receive TN-depleted PBSC from a MUD following lower-intensity myeloablative conditioning (TBI 400 cGy, thiotepa, fludarabine and cyclophosphamide) and pharmacological immunosuppression with tacrolimus and MMF.

II. To estimate the probability of acute (a)GVHD grade II-IV following TN-depleted (TND) PBSCT with tacrolimus and methotrexate (Arm A) or MMF (Arm B) GVHD prophylaxis in MRD recipients.

III. Estimate the rate of aGVHD grade II-IV following TND PBSCT with tacrolimus and methotrexate (Arm C) or MMF (Arm D) prophylaxis in recipients of MUD hematopoietic cell transplantation (HCT).

IV. Estimate the probability of graft failure in recipients of CD45RA positive (+) TN-depleted PBSCT with tacrolimus and methotrexate (MTX) or MMF GVHD prophylaxis.

SECONDARY OBJECTIVES:

I. Estimate the probability of transplant-related mortality by day 100.

II. Estimate the probability of relapse.

III. Evaluate immune reconstitution and pathogen-specific immune reconstitution.

OUTLINE: Patients are assigned to 1 of 4 treatment arms.

CONDITIONING:

ARMS A AND C (high-intensity myeloablative conditioning): Patients undergo total body irradiation twice daily (BID) on days -10 to -7. Patients also receive thiotepa intravenously (IV) over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.

ARMS B AND D (lower-intensity myeloablative conditioning): Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation once daily (QD) on days -2 and -1.

TRANSPLANT: In all arms, patients undergo allogeneic HSCT with granulocyte colony-stimulating factor (GCSF)-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.

GVHD PROPHYLAXIS:

ARMS A AND C: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or orally (PO) (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

ARMS B AND D: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on days -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the principal investigator.

After completion of study treatment, patients are followed up at 80-100 days, 360 days, and then yearly for up to 5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Acute Biphenotypic Leukemia
  • Acute Leukemia of Ambiguous Lineage
  • Acute Undifferentiated Leukemia
  • Allogeneic Hematopoietic Stem Cell Transplant Recipient
  • Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Blastic Plasmacytoid Dendritic Cell Neoplasm
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Childhood Acute Myeloid Leukemia in Remission
  • Donor
  • Lymphoblastic Lymphoma
  • Myelodysplastic Syndrome With Excess Blasts
  • Myelodysplastic Syndrome With Excess Blasts-1
  • Myelodysplastic Syndrome With Excess Blasts-2
  • Recurrent Acute Lymphoblastic Leukemia
  • Recurrent Acute Myeloid Leukemia
  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Refractory Acute Lymphoblastic Leukemia
  • Refractory Acute Myeloid Leukemia
  • Acute Lymphoblastic Leukemia in Remission
  • Acute Myeloid Leukemia in Remission
Intervention  ICMJE
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    Undergo allogeneic HSCT
    Other Names:
    • Allogeneic Hematopoietic Cell Transplantation
    • Allogeneic Stem Cell Transplantation
    • HSC
    • HSCT
  • Drug: Cyclophosphamide
    Given IV
    Other Names:
    • (-)-Cyclophosphamide
    • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    • Carloxan
    • Ciclofosfamida
    • Ciclofosfamide
    • Cicloxal
    • Clafen
    • Claphene
    • CP monohydrate
    • CTX
    • CYCLO-cell
    • Cycloblastin
    • Cycloblastine
    • Cyclophospham
    • Cyclophosphamid monohydrate
    • Cyclophosphamidum
    • Cyclophosphan
    • Cyclophosphane
    • Cyclophosphanum
    • Cyclostin
    • Cyclostine
    • Cytophosphan
    • Cytophosphane
    • Cytoxan
    • Fosfaseron
    • Genoxal
    • Genuxal
    • Ledoxina
    • Mitoxan
    • Neosar
    • Revimmune
    • Syklofosfamid
    • WR- 138719
  • Drug: Fludarabine Phosphate
    Given IV
    Other Names:
    • 2-F-ara-AMP
    • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
    • Beneflur
    • Fludara
    • SH T 586
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Methotrexate
    Given IV
    Other Names:
    • Abitrexate
    • Alpha-Methopterin
    • Amethopterin
    • Brimexate
    • CL 14377
    • CL-14377
    • Emtexate
    • Emthexat
    • Emthexate
    • Farmitrexat
    • Fauldexato
    • Folex
    • Folex PFS
    • Lantarel
    • Ledertrexate
    • Lumexon
    • Maxtrex
    • Medsatrexate
    • Metex
    • Methoblastin
    • Methotrexate LPF
    • Methotrexate Methylaminopterin
    • Methotrexatum
    • Metotrexato
    • Metrotex
    • Mexate
    • Mexate-AQ
    • MTX
    • Novatrex
    • Rheumatrex
    • Texate
    • Tremetex
    • Trexeron
    • Trixilem
    • WR-19039
  • Drug: Mycophenolate Mofetil
    Given IV and PO
    Other Names:
    • Cellcept
    • MMF
  • Procedure: Peripheral Blood Stem Cell Transplantation
    Undergo PBSCT with GCSF-mobilized CD34-enriched PBSC
    Other Names:
    • PBPC transplantation
    • PBSCT
    • Peripheral Blood Progenitor Cell Transplantation
    • Peripheral Stem Cell Support
    • Peripheral Stem Cell Transplant
    • Peripheral Stem Cell Transplantation
  • Procedure: Peripheral Blood Stem Cell Transplantation
    Undergo PBSCT with CD45RA-depleted cells
    Other Names:
    • PBPC transplantation
    • PBSCT
    • Peripheral Blood Progenitor Cell Transplantation
    • Peripheral Stem Cell Support
    • Peripheral Stem Cell Transplant
    • Peripheral Stem Cell Transplantation
  • Drug: Tacrolimus
    Given IV or PO
    Other Names:
    • FK 506
    • Fujimycin
    • Hecoria
    • Prograf
    • Protopic
  • Drug: Thiotepa
    Given IV
    Other Names:
    • 1,1',1''-Phosphinothioylidynetrisaziridine
    • Girostan
    • N,N', N''-Triethylenethiophosphoramide
    • Oncotiotepa
    • STEPA
    • Tepadina
    • TESPA
    • Tespamin
    • Tespamine
    • Thio-Tepa
    • Thiofosfamide
    • Thiofozil
    • Thiophosphamide
    • Thiophosphoramide
    • Thiotef
    • Tifosyl
    • TIO TEF
    • Tio-tef
    • Triethylene thiophosphoramide
    • Triethylenethiophosphoramide
    • Tris(1-aziridinyl)phosphine sulfide
    • TSPA
    • WR 45312
  • Radiation: Total-Body Irradiation
    Undergo TBI
    Other Names:
    • Total Body Irradiation
    • Whole-Body Irradiation
    • TBI
    • Whole Body Irradiation
Study Arms  ICMJE
  • Experimental: Arm A (MRD)

    HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.

    TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.

    GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

    Interventions:
    • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    • Drug: Cyclophosphamide
    • Drug: Fludarabine Phosphate
    • Other: Laboratory Biomarker Analysis
    • Drug: Methotrexate
    • Procedure: Peripheral Blood Stem Cell Transplantation
    • Procedure: Peripheral Blood Stem Cell Transplantation
    • Drug: Tacrolimus
    • Drug: Thiotepa
    • Radiation: Total-Body Irradiation
  • Experimental: Arm B (MRD)

    LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1.

    TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.

    GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator.

    Interventions:
    • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    • Drug: Cyclophosphamide
    • Drug: Fludarabine Phosphate
    • Other: Laboratory Biomarker Analysis
    • Drug: Mycophenolate Mofetil
    • Procedure: Peripheral Blood Stem Cell Transplantation
    • Procedure: Peripheral Blood Stem Cell Transplantation
    • Drug: Tacrolimus
    • Drug: Thiotepa
    • Radiation: Total-Body Irradiation
  • Experimental: Arm C (MUD)

    HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.

    TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.

    GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

    Interventions:
    • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    • Drug: Cyclophosphamide
    • Drug: Fludarabine Phosphate
    • Other: Laboratory Biomarker Analysis
    • Drug: Methotrexate
    • Procedure: Peripheral Blood Stem Cell Transplantation
    • Procedure: Peripheral Blood Stem Cell Transplantation
    • Drug: Tacrolimus
    • Drug: Thiotepa
    • Radiation: Total-Body Irradiation
  • Experimental: Arm D (MUD)

    LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1.

    TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.

    GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator.

    Interventions:
    • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    • Drug: Cyclophosphamide
    • Drug: Fludarabine Phosphate
    • Other: Laboratory Biomarker Analysis
    • Drug: Mycophenolate Mofetil
    • Procedure: Peripheral Blood Stem Cell Transplantation
    • Procedure: Peripheral Blood Stem Cell Transplantation
    • Drug: Tacrolimus
    • Drug: Thiotepa
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 23, 2020)
84
Original Estimated Enrollment  ICMJE
 (submitted: August 18, 2014)
80
Estimated Study Completion Date  ICMJE April 1, 2025
Estimated Primary Completion Date April 1, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients who are considered appropriate candidates for allogeneic hematopoietic stem cell transplantation and have one of the following diagnoses:

    • Acute lymphocytic leukemia in first or subsequent remission
    • Acute myeloid leukemia in first or subsequent remission
    • Acute lymphocytic leukemia in relapse or primary refractory disease with a circulating blast count of no more than 10,000/mm^3 (Arms A or C only)
    • Acute myeloid leukemia in relapse or primary refractory disease with a circulating blast count of no more than 10,000/mm^3 (Arms A or C only)
    • Refractory anemia with excess blasts (RAEB-1 and RAEB-2) (if the patient has received previous induction chemotherapy within 60 days)
    • Chronic myelogenous leukemia with a history of accelerated phase or blast crisis (if the patient has received at least one course of induction chemotherapy)
    • Other acute leukemia or related neoplasm (including but not limited to 'biphenotypic', 'undifferentiated' or 'ambiguous lineage' acute leukemia, blastic plasmacytoid dendritic cell neoplasm or lymphoblastic lymphoma)
  • Patients 0-49 years old will be enrolled in Arm A or C (high-intensity)
  • Patients 50-60 years old will be enrolled in Arm B or D (lower intensity); patients eligible for Arms B or D also include those who have received previous allogeneic HCT, or who have co-morbid conditions rendering them unsuitable for high-dose conditioning, determined in consultation with the principal investigator
  • Patient with a HLA-matched (HLA-A, B, C, and DR beta 1 [DRB1] molecularly matched) unrelated donor or related donor capable of donating PBSC
  • DONOR INCLUSION:
  • HLA-matched related donors >= 18 years and capable and willing to donate PBSC (Arms A and B)
  • HLA-matched unrelated donors (HLA-A, B, C, and DRB1 matched based on high-resolution typing) capable and willing to donate PBSC (Arms C and D)

Exclusion Criteria:

  • Patients with central nervous system (CNS) involvement refractory to intrathecal chemotherapy and/or standard cranial-spinal radiation
  • Patients on other experimental protocols for prevention of acute GVHD
  • Patient weight >= 100 kg; patients >= 70 kg with MUDs must be discussed with the principal investigator
  • Patients who are human immunodeficiency virus positive (HIV+)
  • Patients with uncontrolled infections for whom myeloablative HCT is considered contraindicated by the consulting infectious disease physician (upper respiratory tract viral infection does not constitute an uncontrolled infection in this context)
  • Patients with organ dysfunction
  • ARM A OR C EXCLUSION:
  • Creatinine > 1.5 mg/dl at the present time; patients with a known history of creatinine > 1.5 mg/dl must have a current estimated creatinine clearance of > 40 ml/min
  • Cardiac ejection fraction < 45%
  • Diffusing capacity of the lung for carbon monoxide (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 tests (LFTs) (including total bilirubin, aspartate aminotransferase [AST] and 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, methotrexate, Bactrim or another drug); if the GI physician considers that HCT on the high-intensity arms of protocol is contraindicated for that patient the patient may be considered for treatment on the lower intensity arm of the protocol or excluded from the protocol; patients with Gilbert's syndrome and no other known liver function abnormality and patients with reversible drug-related transaminitis do not necessarily require GI consultation and may be included on the high-intensity arms of the protocol
  • ARM B OR D EXCLUSION:
  • Creatinine > 2.0 mg/dl at the present time; patients with a known history of creatinine > 1.5 mg/dl must have a current estimated creatinine clearance > 40 ml/min
  • Cardiac ejection fraction < 35%
  • DLCO corrected < 50%; patients who are unable to perform pulmonary function tests (for example, due to young age and/or developmental status) will be excluded if the O2 saturation is < 92% on room air; patients with a DLCO 50-60% must also have a partial pressure of oxygen (pO2) of > 80 mmHg
  • Liver function abnormality; patients who have LFTs >= twice the upper limit of normal should be evaluated by a GI physician unless there is a clear precipitating factor (such as an azole, methotrexate, Bactrim or another drug); patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excluded
  • Patients will be excluded from Arms A and C if they have received a previous myeloablative transplant; patients who have received a prior HCT at least 6 months prior may be considered for inclusion on Arms B or D after discussion with the principal investigator (PI)
  • Patients with a life expectancy < 3 months from co-existing disease other than the leukemia or RAEB
  • Patients who are pregnant or breast-feeding
  • Fertile patients of child bearing age unwilling to use contraception during and for 12 months post-transplant
  • Patients with a significant other medical conditions that would make them unsuitable for transplant
  • Patients with a known hypersensitivity to tacrolimus, methotrexate (Arm A or C) or MMF (Arm B or D)
  • DONOR EXCLUSION:
  • Donors who are HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1, HTLV-2 seropositive or with active hepatitis B or hepatitis C virus infection
  • Donors who fail eligibility requirements for donation of cells or tissue for donation of a Human Cell and Tissue Products (HCT/P) will be excluded unless use of the cells complies urgent medical need or allogeneic use in a first-degree or second-degree relative
  • Unrelated donors donating outside of the United States of America (USA)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 60 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02220985
Other Study ID Numbers  ICMJE 2684.00
NCI-2014-01301 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2684.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
K23CA154532 ( U.S. NIH Grant/Contract )
P30CA015704 ( U.S. NIH Grant/Contract )
R01HL121568 ( U.S. NIH Grant/Contract )
RG9214012 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fred Hutchinson Cancer Research Center
Study Sponsor  ICMJE Fred Hutchinson Cancer Research Center
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Marie Bleakley Fred Hutch/University of Washington Cancer Consortium
PRS Account Fred Hutchinson Cancer Research Center
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP