HLA-Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation With Reduced Dose Post Transplantation Cyclophosphamide GvHD Prophylaxis (OPTIMIZE)

April 8, 2024 updated by: Center for International Blood and Marrow Transplant Research

A Phase II Study of Reduced Dose Post Transplantation Cyclophosphamide as GvHD Prophylaxis in Adult Patients With Hematologic Malignancies Receiving HLA-Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

The goal of this clinical trial is to determine the effectiveness of Reduced Dose Post-Transplant Cyclophosphamide (PTCy) in patients with hematologic malignancies after receiving an HLA-Mismatched Unrelated Donor (MMUD) . The main question[s] it aims to answer are:

  • Does a reduced dose of PTCy reduce the occurrence of infections in the first 100 days after transplant?
  • Does a reduced dose of PTCy maintain the same level of protection against Graft Versus Host Disease (GvHD) as the standard dose of PTCy?

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

190

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Contact:
        • Principal Investigator:
          • Monzr AlMalki, MD
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Not yet recruiting
        • Mayo Clinic - Jacksonville
        • Principal Investigator:
          • Hemant Murthy, MD
        • Contact:
      • Miami, Florida, United States, 33136
        • Not yet recruiting
        • University of Miami Sylvester Cancer Center
        • Contact:
          • Antonio M Jimenez Jimenez, MD
      • Tampa, Florida, United States, 33612
        • Not yet recruiting
        • Moffitt Cancer Center
        • Principal Investigator:
          • Farhad Khimani, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Not yet recruiting
        • Dana Farber Cancer Institute
        • Contact:
          • Mahasweta Gooptu, MD
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Karmanos Cancer Institute
        • Principal Investigator:
          • Dipenkumar Modi, MD
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • University of Minnesota
        • Contact:
        • Principal Investigator:
          • Mark Juckett, MD
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Barnes Jewish Hospital / Washington University
        • Contact:
        • Principal Investigator:
          • Ramzi Abboud, MD
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center - Adults
        • Principal Investigator:
          • Brian Shaffer, MD
        • Contact:
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Not yet recruiting
        • University of North Carolina
        • Contact:
        • Principal Investigator:
          • Katarzyna Jamieson, MD
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health & Science University
        • Contact:
        • Principal Investigator:
          • Rachel J Cook, M.D.
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Principal Investigator:
          • Betul Oran, MD
        • Contact:
          • Betul Oran, MD
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia Health System
        • Principal Investigator:
          • Karen Ballen, MD
        • Contact:
          • Karen Ballen, M.D.
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Center
        • Contact:
        • Principal Investigator:
          • Masumi Ueda Oshima, MD
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Not yet recruiting
        • Froedtert & the Medical College of Wisconsin
        • Contact:
          • Sameem Abedin, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Stratum 1 Recipient Inclusion Criteria:

  1. Age ≥ 18 years and < 66 years (chemotherapy-based conditioning) or < 61 years (total body irradiation [TBI]-based conditioning) at the time of signing informed consent
  2. Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and institutional requirements.
  3. Stated willingness to comply with all study procedures and availability for the duration of the study.
  4. Planned MAC regimen as defined per study protocol
  5. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age ≥ 18 and ≤ 40 years (≤ 35 preferred).
  6. Product planned for infusion is MMUD T-cell replete PBSC allograft
  7. HCT-CI < 5. The presence of prior malignancy will not be used to calculate HCT-CI for this trial to allow for the inclusion of patients with secondary or therapy-related AML or MDS.

  8. One of the following diagnoses:

    1. Acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or other acute leukemia in 1st remission or beyond with ≤ 5% marrow blasts and no circulating blasts or evidence of extra-medullary disease. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
    2. Patients with MDS with no circulating blasts and with < 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with < 5% or 5-10% blasts in MDS). Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
  9. Cardiac function: Left ventricular ejection fraction ≥ 45% based on most recent echocardiogram or multi-gated acquisition scan (MUGA) results.
  10. Estimated creatinine clearance ≥ 45mL/min calculated by equation.
  11. Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin > 50% and forced expiratory volume in first second (FEV1) predicted > 50% based on most recent pulmonary function test (PFT) results
  12. Liver function acceptable per local institutional guidelines
  13. KPS of ≥ 70%

Stratum 2 Recipient Inclusion Criteria:

  1. Age ≥18 years at the time of signing informed consent
  2. Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and local institutional requirements.
  3. Stated willingness to comply with all study procedures and availability for the duration of the study.
  4. Planned NMA/RIC regimen per study protocol
  5. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age ≥ 18 and ≤ 40 years (≤ 35 preferred).
  6. Product planned for infusion is MMUD T-cell replete PBSC allograft

  7. One of the following diagnoses:

    1. Patients with acute leukemia or chronic myeloid leukemia (CML) with no circulating blasts, no evidence of extramedullary disease, and with < 5% blasts in the bone marrow.

      Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.

    2. Patients with MDS with no circulating blasts and with < 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with < 5% or 5-10% blasts in MDS.) Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
    3. Patients with chronic lymphocytic leukemia (CLL) or other leukemias (including prolymphocytic leukemia) with chemosensitive disease at time of transplantation
    4. Higher risk CMML according to CMML-specific prognostic scoring system or high risk MDS/MPN not otherwise specified are eligible, provided there is no evidence of high-grade bone marrow fibrosis or massive splenomegaly at the time of enrollment.
    5. Patients with lymphoma with chemosensitive disease at the time of transplantation
  8. Cardiac function: Left ventricular ejection fraction ≥ 40% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure
  9. Estimated creatinine clearance ≥ 45mL/min calculated by equation
  10. Pulmonary function: DLCO corrected for hemoglobin > 50% and FEV1 predicted >50% based on most recent PFT results
  11. Liver function acceptable per local institutional guidelines
  12. KPS of ≥ 60%

Stratum 3 Recipient Inclusion Criteria:

  1. Age ≥18 years at the time of signing informed consent
  2. Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and local institutional requirements.
  3. Stated willingness to comply with all study procedures and availability for the duration of the study.
  4. Planned NMA/RIC regimen per study protocol
  5. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age ≥ 18 and ≤ 40 years (≤ 35 preferred).
  6. Product planned for infusion is MMUD T-cell replete PBSC allograft
  7. Diagnosis of primary myelofibrosis with risk features making them eligible for HCT. Myelofibrosis secondary to essential thrombocythemia, polycythemia vera, or MDS with grade 4 fibrosis are also eligible. Patients with a myelofibrosis diagnosis require sponsor approval before enrolling.
  8. Cardiac function: Left ventricular ejection fraction ≥ 40% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure
  9. Estimated creatinine clearance ≥ 45 mL/min calculated by equation
  10. Pulmonary function: DLCO corrected for hemoglobin > 50% and FEV1 predicted >50% based on most recent PFT results
  11. Liver function acceptable per local institutional guidelines
  12. KPS of ≥ 60%

Donor Inclusion Criteria (note: donors are not research subjects):

  1. Must be unrelated to the subject and high-resolution HLA-matched at 4/8, 5/8, 6/8, or 7/8 (HLA-A, -B, -C, and -DRB1.
  2. Donor must be typed at high-resolution for a minimum of HLA-A, -B, -C, -DQB1, and -DPB1.
  3. Age ≥ 18 years and ≤ 40 years at the time of signing informed consent for PBSC donation. Note: donors are preferred to be ≤ 35.
  4. Meet the donor registries' medical suitability requirements for PBSC donation.
  5. Must undergo eligibility screening according to current Food and Drug Administration (FDA) requirements. Donors who do not meet one or more of the donor screening requirements may donate under urgent medical need.
  6. Must agree to donate PBSC.
  7. Must have the ability to give informed consent according to standard (non-study) informed consent according to applicable donor regulatory requirements.

Recipient Exclusion Criteria (Strata 1, 2, and 3):

  1. Suitable HLA-matched related or 8/8 high-resolution matched unrelated donor available
  2. Subject unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing
  3. Subjects with a prior allogeneic transplant
  4. Subjects with an autologous transplant within the past 3 months
  5. Females who are breast-feeding or pregnant
  6. Uncontrolled bacterial, viral, or fungal infection at the time of the transplant preparative regimen
  7. Concurrent enrollment on a preventative GvHD and/or infectious disease prevention clinical trial.
  8. Subjects who undergo desensitization to reduce anti-donor HLA antibody levels prior to transplant.
  9. Patients who are HIV+ with persistently positive viral load. HIV-infected patients on effective anti-retroviral therapy (ART) with undetectable viral load within 6 months are eligible for this trial. Patients with well controlled HIV are eligible provided resistance panels are negative, the patient is compliant with ART, and their disease remains well controlled.

Donor Exclusion Criteria:

  1. Donor unwilling or unable to donate.
  2. Recipient positive for HLA antibodies against a mismatched HLA in the selected donor determined by the presence of donor specific HLA antibodies (DSA) to any mismatched HLA allele/antigen at any of the following loci (HLA-A, -B, -C, -DRB1, DRB3, DRB4, DRB5, -DQA1, - DQB1, -DPA1, -DPB1) with median fluorescence intensity (MFI) >3000 by microarray-based single antigen bead testing. In patients receiving red blood cell or platelet transfusions, DSA evaluation must be performed or repeated post-transfusion and prior to donor mobilization and initiation of recipient preparative regimen.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy

Patients Receive:

Patients receive:

Busulfan (≥ 9 mg/kg total dose) IV or PO on days -6 to -3 Fludarabine (150 mg/m2 total dose) IV on days -6 to -2

Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.

Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.

First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
Drug: Busulfan
Given IV or PO pre-transplant as part of conditioning regimen
Other Names:
  • Busulfex®
Drug: Fludarabine
Given IV pre-transplant as part of conditioning regimen
Other Names:
  • Fludara®
Drug: Mycophenolate Mofetil
Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
Other Names:
  • MMF
  • Cellcept®
Procedure: PBSC Hematopoietic Stem Cell Transplantation (HSCT)
Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0
Other Names:
  • PBSCT
  • PBSC HSCT
  • PBSC HCT
  • PBSC Transplantation
Drug: Tacrolimus
Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at Day + 90 and finished by Day +180.
Other: Patient Reported Outcomes
Survey assessments will be administered to study participants pre transplant, at Day + 100, Day + 180, and Day +365 post transplant.
Other Names:
  • PRO
Drug: Post-Transplant Cyclophosphamide

Cyclophosphamide (25mg/kg) is administered on Day 3 and Day 4 post-transplant as an IV infusion over 1-2 hours.

First 20 subjects with a 4-6/8 HLA mismatched unrelated donor will receive an intermediate dose of post-transplant cyclophosphamide of 37.5 mg/kg Day 3 and Day 4 post-transplant.

Other Names:
  • Cytoxan®
  • PTCy
Experimental: Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy

Patients receive:

Fludarabine (90 mg/m2 total dose) IV on days -7 to -5 Total body irradiation (TBI) (1200 cGy total dose) on days -4 to -1

Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.

Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.

First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
Drug: Fludarabine
Given IV pre-transplant as part of conditioning regimen
Other Names:
  • Fludara®
Drug: Mycophenolate Mofetil
Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
Other Names:
  • MMF
  • Cellcept®
Radiation: Total-body irradiation
Administered pre-transplant as part of conditioning regimen
Other Names:
  • TBI
Procedure: PBSC Hematopoietic Stem Cell Transplantation (HSCT)
Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0
Other Names:
  • PBSCT
  • PBSC HSCT
  • PBSC HCT
  • PBSC Transplantation
Drug: Tacrolimus
Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at Day + 90 and finished by Day +180.
Other: Patient Reported Outcomes
Survey assessments will be administered to study participants pre transplant, at Day + 100, Day + 180, and Day +365 post transplant.
Other Names:
  • PRO
Drug: Post-Transplant Cyclophosphamide

Cyclophosphamide (25mg/kg) is administered on Day 3 and Day 4 post-transplant as an IV infusion over 1-2 hours.

First 20 subjects with a 4-6/8 HLA mismatched unrelated donor will receive an intermediate dose of post-transplant cyclophosphamide of 37.5 mg/kg Day 3 and Day 4 post-transplant.

Other Names:
  • Cytoxan®
  • PTCy
Experimental: Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy

Patients receive:

Fludarabine (150-180 mg/m2 total dose) IV on days -6 to -2 Busulfan (less than or equal to 8 mg/kg PO or 6.4 mg/kg IV) on days -5 and -4

Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.

Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.

First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
Drug: Busulfan
Given IV or PO pre-transplant as part of conditioning regimen
Other Names:
  • Busulfex®
Drug: Fludarabine
Given IV pre-transplant as part of conditioning regimen
Other Names:
  • Fludara®
Drug: Mycophenolate Mofetil
Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
Other Names:
  • MMF
  • Cellcept®
Procedure: PBSC Hematopoietic Stem Cell Transplantation (HSCT)
Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0
Other Names:
  • PBSCT
  • PBSC HSCT
  • PBSC HCT
  • PBSC Transplantation
Drug: Tacrolimus
Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at Day + 90 and finished by Day +180.
Other: Patient Reported Outcomes
Survey assessments will be administered to study participants pre transplant, at Day + 100, Day + 180, and Day +365 post transplant.
Other Names:
  • PRO
Drug: Post-Transplant Cyclophosphamide

Cyclophosphamide (25mg/kg) is administered on Day 3 and Day 4 post-transplant as an IV infusion over 1-2 hours.

First 20 subjects with a 4-6/8 HLA mismatched unrelated donor will receive an intermediate dose of post-transplant cyclophosphamide of 37.5 mg/kg Day 3 and Day 4 post-transplant.

Other Names:
  • Cytoxan®
  • PTCy
Experimental: Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy

Patients receive:

Fludarabine (125-150 mg/m2 total dose) IV on days -7 to -3 Melphalan (100-140 mg/m2) IV on day -1

Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.

Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.

First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
Drug: Fludarabine
Given IV pre-transplant as part of conditioning regimen
Other Names:
  • Fludara®
Drug: Mycophenolate Mofetil
Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
Other Names:
  • MMF
  • Cellcept®
Procedure: PBSC Hematopoietic Stem Cell Transplantation (HSCT)
Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0
Other Names:
  • PBSCT
  • PBSC HSCT
  • PBSC HCT
  • PBSC Transplantation
Drug: Tacrolimus
Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at Day + 90 and finished by Day +180.
Other: Patient Reported Outcomes
Survey assessments will be administered to study participants pre transplant, at Day + 100, Day + 180, and Day +365 post transplant.
Other Names:
  • PRO
Drug: Melphalan
Given IV pre transplant as part of conditioning regimen
Drug: Post-Transplant Cyclophosphamide

Cyclophosphamide (25mg/kg) is administered on Day 3 and Day 4 post-transplant as an IV infusion over 1-2 hours.

First 20 subjects with a 4-6/8 HLA mismatched unrelated donor will receive an intermediate dose of post-transplant cyclophosphamide of 37.5 mg/kg Day 3 and Day 4 post-transplant.

Other Names:
  • Cytoxan®
  • PTCy
Experimental: Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy

Patients receive:

Fludarabine (150mg/m2 total dose) IV on days -6 to -2 Cyclophosphamide (29-50mg/kg) IV on days -6 and -5 TBI (200cGy) on day -1

Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.

Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.

First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
Drug: Fludarabine
Given IV pre-transplant as part of conditioning regimen
Other Names:
  • Fludara®
Drug: Mycophenolate Mofetil
Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
Other Names:
  • MMF
  • Cellcept®
Radiation: Total-body irradiation
Administered pre-transplant as part of conditioning regimen
Other Names:
  • TBI
Drug: Cyclophosphamide
Given IV pre-transplant as part of conditioning regimen
Other Names:
  • Cytoxan®
Procedure: PBSC Hematopoietic Stem Cell Transplantation (HSCT)
Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0
Other Names:
  • PBSCT
  • PBSC HSCT
  • PBSC HCT
  • PBSC Transplantation
Drug: Tacrolimus
Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at Day + 90 and finished by Day +180.
Other: Patient Reported Outcomes
Survey assessments will be administered to study participants pre transplant, at Day + 100, Day + 180, and Day +365 post transplant.
Other Names:
  • PRO
Drug: Mesna
Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post cyclophosphamide.
Other Names:
  • Mesnex®
Drug: Post-Transplant Cyclophosphamide

Cyclophosphamide (25mg/kg) is administered on Day 3 and Day 4 post-transplant as an IV infusion over 1-2 hours.

First 20 subjects with a 4-6/8 HLA mismatched unrelated donor will receive an intermediate dose of post-transplant cyclophosphamide of 37.5 mg/kg Day 3 and Day 4 post-transplant.

Other Names:
  • Cytoxan®
  • PTCy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Infection Free Survival
Time Frame: 100 days post-HCT
Survival at 100 days without grades 2-3 infections (per BMT CTN grading criteria)
100 days post-HCT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 1-year post-HCT
Defined as time interval between date of transplant and death from any cause
1-year post-HCT
Progression-free survival
Time Frame: 1-year post-HCT
Defined as disease relapse or progression, or death by any cause
1-year post-HCT
Infection-free survival
Time Frame: 1-year post-HCT
Defined as death and grades II-III infection (per BMT CTN criteria)
1-year post-HCT
Graft versus host disease relapse free survival
Time Frame: 1-year post-HCT
Defined as relapse or progression of underling disease (by 1 year), grade III-IV acute GvHD (by 6 months), chronic GvHD requiring systemic immune suppression (by 1 year), or death by any cause (by 1 year).
1-year post-HCT
Non-relapse mortality
Time Frame: 1-year post-HCT
Defined as death without evidence of disease progression or recurrence
1-year post-HCT
Cumulative incidence of neutrophil recovery
Time Frame: Day 28 post-HCT
Defined as achieving an absolute neutrophil count (ANC) greater than or equal to 500/mm3 for three consecutive measurements on three different days
Day 28 post-HCT
Cumulative incidence of platelet recovery
Time Frame: Day 28 post-HCT
Defined as platelet count ≥20,000/mm^3 or ≥50,000/mm^3 with no platelet transfusions within seven days.
Day 28 post-HCT
Cumulative incidence of primary and secondary graft failure
Time Frame: Day 28 and 1-year post-HCT

Primary graft failure is defined as no neutrophil recovery to ≥ 500 cells/mm3 by Day 28 post HCT.

Secondary graft failure is defined as as initial neutrophil count recovery followed by subsequent decline in absolute neutrophil counts <500 cells/mm3, unresponsive to growth factor therapy, but cannot be explained by infection, disease relapse, or medications.
Day 28 and 1-year post-HCT
Donor T-Cell Chimerism
Time Frame: Day 28, 100 and 365 post-HCT
Defined as percent of donor chimerism via peripheral blood
Day 28, 100 and 365 post-HCT
Cumulative incidence of acute GvHD
Time Frame: Day 100 and Day 180 post-HCT
Defined as cumulative incidence of grades II-IV acute GvHD
Day 100 and Day 180 post-HCT
Cumulative incidence of chronic GvHD
Time Frame: 1-year post-HCT
1-year post-HCT
Cumulative incidence of grade 2-3 bacterial, fungal, and viral infections
Time Frame: Day 100 and 1-year post-HCT
Defined as grades 2-3 infection as defined by BMT CTN grading criteria.
Day 100 and 1-year post-HCT
Cumulative incidence of grades 2-3 BK virus hemorrhagic cystitis
Time Frame: 1-year post-HCT
Defined as incidence of BK virus hemorrhagic cystitis per BMT CTN grading criteria
1-year post-HCT
Cumulative incidence of relapse/progression
Time Frame: 1-year post-HCT
Defined as disease relapse or progression from Day 0 to 1-year post-HCT
1-year post-HCT
Overall Toxicity
Time Frame: 1-year post-HCT
To tabulate adverse events (AEs, experienced by recipients, defined as grade 3-5 unexpected and grade 5 expected AEs according to CTCAE v5
1-year post-HCT
Incidence and Severity of cytokine release syndrome
Time Frame: within 14 days post-HCT
Defined and graded using the ASTCT grading criteria.
within 14 days post-HCT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Center for International Blood and Marrow Transplant Research

Collaborators

National Marrow Donor Program

Investigators

  • Principal Investigator: Steven Devine, MD, NMDP
  • Study Chair: Jeffery Auletta, MD, NMDP

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 8, 2023

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

June 30, 2026

Study Registration Dates

First Submitted

August 14, 2023

First Submitted That Met QC Criteria

August 14, 2023

First Posted (Actual)

August 21, 2023

Study Record Updates

Last Update Posted (Actual)

April 9, 2024

Last Update Submitted That Met QC Criteria

April 8, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OPTIMIZE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lymphoma

Clinical Trials on Busulfan

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Chile

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe