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

Overview

About this study

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?

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/12/23. Questions regarding updates should be directed to the study team contact

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Hassan Alkhateeb, M.D.

Open for enrollment

Contact information:

Jennifer Hull

(507) 422-4820

Hull.Jennifer2@mayo.edu

Jacksonville, Fla.

Mayo Clinic principal investigator

Hemant Murthy, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Saurabh Chhabra, M.B.B.S.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
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CLS-20571744

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