Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

HLA-Mismatched Unrelated Donor Bone Marrow Transplantation With Post-Transplantation Cyclophosphamide

Protocol: OSU-16165

Full Title

A Multi-Center, Phase II Trial of HLA-Mismatched Unrelated Donor Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide for Patients with Hematologic Malignancies

Purpose

This is a multi-center, single arm Phase II study of hematopoietic cell transplantation

(HCT) using human leukocyte antigen (HLA)-mismatched unrelated bone marrow transplantation

donors and post-transplantation cyclophosphamide (PTCy), sirolimus and mycophenolate mofetil

(MMF) for graft versus host disease (GVHD) prophylaxis in patients with hematologic

malignancies.

Are you eligible?

Inclusion Criteria:

Inclusion Criteria:

1. Age ≥ 15 years and < 71 years at the time of signing the informed consent form

2. Partially HLA-mismatched unrelated donor: HLA typing will be performed at high

resolution (allele level) for the HLA-A, -B, -C, and -DRB1 loci; a minimum match of

4/8 at HLA-A, -B, -C, and -DRB1 is required

3. Product planned for infusion is bone marrow

4. Disease and disease status:

1. Acute Leukemias or T lymphoblastic lymphoma in 1st or subsequent complete

remission (CR): Acute lymphoblastic leukemia (ALL)/T lymphoblastic lymphoma;

acute myelogenous leukemia (AML); acute biphenotypic leukemia (ABL); acute

undifferentiated leukemia (AUL)

2. Myelodysplastic Syndrome (MDS), fulfilling the following criteria: Subjects with

de novo MDS who have or have previously had Intermediate-2 or High risk disease

as determined by the International Prognostic Scoring System (IPSS). Current

Intermediate-2 or High risk disease is not a requirement; Subjects must have <

20% bone marrow blasts, assessed within 60 days of informed consent; Subjects

may have received prior therapy for the treatment of MDS prior to enrollment

3. Chronic Lymphocytic Leukemia (CLL) in CR if RIC is to be used; in CR or partial

response (PR) if FIC is to be used

4. Chemotherapy-sensitive lymphoma in status other than 1st CR

5. Performance status: Karnofsky or Lansky score ≥ 60% (Appendix A)

6. Adequate organ function defined as:

1. Cardiac: left ventricular ejection fraction (LVEF) at rest ≥ 35% (RIC cohort) or

LVEF at rest ≥ 40% (FIC cohort), or left ventricular shortening fraction (LVFS)

≥ 25%

2. Pulmonary: diffusing capacity of the lungs for carbon monoxide (DLCO), forced

expiratory volume (FEV1), forced vital capacity (FVC) ≥ 50% predicted by

pulmonary function tests (PFTs)

3. Hepatic: total bilirubin ≤ 2.5 mg/dL, and alanine aminotransferase (ALT),

aspartate aminotransferase (AST), and alkaline phosphatase (ALP) < 5 x upper

limit of (ULN) (unless disease related)

4. Renal: serum creatinine (SCr) within normal range for age (see table 2.3). If

SCr is outside normal range for age, creatinine clearance (CrCl) > 40

mL/min/1.73m2 must be obtained (measured by 24-hour (hr) urine specimen or

nuclear glomerular filtration rate (GFR), or calculated GFR (by Cockcroft-Gault

formula for those aged ≥ 18 years; by Original Schwartz estimate for those < 18

years))

7. Subjects ≥ 18 years of age must have the ability to give informed consent according

to applicable regulatory and local institutional requirements. Legal guardian

permission must be obtained for subjects < 18 years of age. Pediatric subjects will

be included in age appropriate discussion in order to obtain assent.

8. Subjects with documentation of confirmed HIV-1 infection (i.e. HIV-positive), and a

hematologic malignancy who meets all other eligibility requirements must:

1. Receive only RIC regimen (i.e. Regimen A)

2. Be willing to comply with effective antiretroviral therapy (ARV)

3. Have achieved a sustained virologic response for 12 weeks after cessation of

hepatitis C antiviral treatment (in HIV-positive subjects with hepatitis C)

Exclusion Criteria:

1. HLA-matched related or 8/8 allele matched (HLA-A, -B, -C, -DRB1) unrelated donor

available. This exclusion does not apply to HIV-positive subjects who have a

CCR5delta32 homozygous donor.

2. Autologous HCT < 3 months prior to the time of signing the informed consent form

3. Females who are breast-feeding or pregnant

4. HIV-positive subjects:

1. Acquired immunodeficiency syndrome (AIDS) related syndromes or symptoms that may

pose an excessive risk for transplantation-related morbidity as determined by

the Treatment Review Committee (see Appendix D).

2. Untreatable HIV infection due to multidrug ARV resistance. Subjects with a

detectable or standard viral load > 750 copies/mL should be evaluated with an

HIV drug resistance test (HIV-1 genotype). The results should be included as

part of the ARV review (described in Appendix D).

3. May not be currently prescribed ritonavir, cobacistat and/or zidovudine

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Exclusion Criteria:

Inclusion Criteria:

1. Age ≥ 15 years and < 71 years at the time of signing the informed consent form

2. Partially HLA-mismatched unrelated donor: HLA typing will be performed at high

resolution (allele level) for the HLA-A, -B, -C, and -DRB1 loci; a minimum match of

4/8 at HLA-A, -B, -C, and -DRB1 is required

3. Product planned for infusion is bone marrow

4. Disease and disease status:

1. Acute Leukemias or T lymphoblastic lymphoma in 1st or subsequent complete

remission (CR): Acute lymphoblastic leukemia (ALL)/T lymphoblastic lymphoma;

acute myelogenous leukemia (AML); acute biphenotypic leukemia (ABL); acute

undifferentiated leukemia (AUL)

2. Myelodysplastic Syndrome (MDS), fulfilling the following criteria: Subjects with

de novo MDS who have or have previously had Intermediate-2 or High risk disease

as determined by the International Prognostic Scoring System (IPSS). Current

Intermediate-2 or High risk disease is not a requirement; Subjects must have <

20% bone marrow blasts, assessed within 60 days of informed consent; Subjects

may have received prior therapy for the treatment of MDS prior to enrollment

3. Chronic Lymphocytic Leukemia (CLL) in CR if RIC is to be used; in CR or partial

response (PR) if FIC is to be used

4. Chemotherapy-sensitive lymphoma in status other than 1st CR

5. Performance status: Karnofsky or Lansky score ≥ 60% (Appendix A)

6. Adequate organ function defined as:

1. Cardiac: left ventricular ejection fraction (LVEF) at rest ≥ 35% (RIC cohort) or

LVEF at rest ≥ 40% (FIC cohort), or left ventricular shortening fraction (LVFS)

≥ 25%

2. Pulmonary: diffusing capacity of the lungs for carbon monoxide (DLCO), forced

expiratory volume (FEV1), forced vital capacity (FVC) ≥ 50% predicted by

pulmonary function tests (PFTs)

3. Hepatic: total bilirubin ≤ 2.5 mg/dL, and alanine aminotransferase (ALT),

aspartate aminotransferase (AST), and alkaline phosphatase (ALP) < 5 x upper

limit of (ULN) (unless disease related)

4. Renal: serum creatinine (SCr) within normal range for age (see table 2.3). If

SCr is outside normal range for age, creatinine clearance (CrCl) > 40

mL/min/1.73m2 must be obtained (measured by 24-hour (hr) urine specimen or

nuclear glomerular filtration rate (GFR), or calculated GFR (by Cockcroft-Gault

formula for those aged ≥ 18 years; by Original Schwartz estimate for those < 18

years))

7. Subjects ≥ 18 years of age must have the ability to give informed consent according

to applicable regulatory and local institutional requirements. Legal guardian

permission must be obtained for subjects < 18 years of age. Pediatric subjects will

be included in age appropriate discussion in order to obtain assent.

8. Subjects with documentation of confirmed HIV-1 infection (i.e. HIV-positive), and a

hematologic malignancy who meets all other eligibility requirements must:

1. Receive only RIC regimen (i.e. Regimen A)

2. Be willing to comply with effective antiretroviral therapy (ARV)

3. Have achieved a sustained virologic response for 12 weeks after cessation of

hepatitis C antiviral treatment (in HIV-positive subjects with hepatitis C)

Exclusion Criteria:

1. HLA-matched related or 8/8 allele matched (HLA-A, -B, -C, -DRB1) unrelated donor

available. This exclusion does not apply to HIV-positive subjects who have a

CCR5delta32 homozygous donor.

2. Autologous HCT < 3 months prior to the time of signing the informed consent form

3. Females who are breast-feeding or pregnant

4. HIV-positive subjects:

1. Acquired immunodeficiency syndrome (AIDS) related syndromes or symptoms that may

pose an excessive risk for transplantation-related morbidity as determined by

the Treatment Review Committee (see Appendix D).

2. Untreatable HIV infection due to multidrug ARV resistance. Subjects with a

detectable or standard viral load > 750 copies/mL should be evaluated with an

HIV drug resistance test (HIV-1 genotype). The results should be included as

part of the ARV review (described in Appendix D).

3. May not be currently prescribed ritonavir, cobacistat and/or zidovudine

5