Inclusion Criteria:
- Male or female subjects with AML, MDS or mature B cell lymphomas that have relapsed
following matched-related donor (MRD) or matched unrelated donor (MUD) (HLA-A -B -C
-DR -DQ) alloSCT are eligible for enrollment
1. Signed written informed consent
1. Subjects must have signed and dated an IRB-approved written informed consent
form in accordance with regulatory and institutional guidelines. This must
be obtained before the performance of any protocol-related procedures that
are not part of normal subject care.
2. Subjects must be willing and able to comply with scheduled visits, treatment
schedule, laboratory tests and other requirements of the study.
2. Target population
1. Subjects must be ≥ 18 years of age.
2. Subjects must have an ECOG performance status of 0-1 (Appendix).
3. Subjects have undergone alloSCT > 90 days prior to enrollment from a
matched-related donor (MRD), matched-unrelated donor (MUD), cord blood
donor, or haplo-identical and cord blood donor.
4. There must be histological confirmation of relapse after alloSCT of any of
the following diseases: any mature B cell lymphoma (cHL or NHL), AML or MDS.
5. Subjects must be off of all immunosuppressive medications for a minimum of 2
weeks with the exception of physiologic doses of corticosteroids.
6. Subjects with B cell lymphoma must have measurable disease, defined as at
least 1 lesion that can be accurately measured in at least 2 dimensions with
CT scan. Minimum measurement must be > 15 mm in the longest diameter and >
10 mm in the short axis.
7. Subjects must not have had any prior investigational agents or devices
within 4 weeks of beginning study drug
8. Subjects must have no prior history of VOD
9. Subjects must demonstrate adequate organ function as defined below. All
screening labs should be performed within 10 days of treatment initiation.
Hematological Absolute neutrophil count (ANC) ≥ 500 /mcL Platelets ≥ 20,000
/mcL Hemoglobin ≥ 8 g/dL (RBC transfusions are OK)
Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR
can also be used in place of creatinine or CrCl) ≤ 1.5 X upper limit of
normal (ULN) or
- 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
Hepatic Serum total bilirubin ≤ 1.5 X ULN or direct bilirubin ≤ ULN for
subjects with total bilirubin levels > 1.5X ULN AST (SGOT) and ALT (SGPT) ≤
2.5 X ULN Albumin ≥ 2.0 mg/dL
Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) ≤
1.5 X ULN unless subject is receiving anticoagulant therapy, in which case,
the PT/INR should be within therapeutic range for intended use. Activated
Partial Thromboplastin Time (aPTT) ≤ 1.5 X ULN unless subject is receiving
anticoagulant therapy, in which case, the PTT should be within therapeutic
range for intended use.
*Creatinine clearance should be calculated per institutional standard.
10. Female subjects of childbearing potential should have a negative urine or
serum pregnancy test (β-hCG) within 72 hours prior to receiving the first
dose of study medication.
11. Female subjects with childbearing potential should be willing to use 2
methods of contraception, be surgically sterile, or abstain from
heterosexual activity throughout the course of the study, until 120 days
after the final dose of study medication. Subjects with childbearing
potential are those who have not been surgically sterilized or have not been
free from menses for > 1 year. Abstinence is acceptable if this is the
established and preferred contraceptive method for the subject.
12. Male subjects should agree to use an adequate method of contraception
starting with the first dose of study medication until 120 days after the
final dose of study medicine. Abstinence is acceptable if this is the
established and preferred contraceptive method for the subject.
Exclusion Criteria:
- 1. Target disease exclusions
1. Subjects must not have known central nervous system involvement by disease
(parenchymal, meningeal or cerebrospinal fluid) 2. Medical history, concurrent
diseases, and prior treatments
1. Subjects must not have a history of any positive test for hepatitis B or
hepatitis C indicating active disease or previous exposure.
2. Subjects must not have a history of human immunodeficiency virus (HIV) infection.
3. Subjects must not be receiving systemic steroid therapy or any other form of
immunosuppressive therapy within 2 weeks prior to the first dose of study
medication. The use of physiologic doses of corticosteroids is acceptable.
4. Subjects must not be concurrently receiving disease-modifying therapy in another
therapeutic investigational study.
5. Subjects must not have received a prior monoclonal antibody within 4 weeks prior
to the first dose of study medication, and must have recovered (≤ grade 1) from
adverse events related to any anti-cancer agent administered > 4 weeks previous
to the first dose of study medication.
6. Subjects must not have received chemotherapy, targeted small molecule therapy, or
radiation therapy within 2 weeks prior to the first dose of study medication, and
must have recovered (≤ grade 1) from adverse events related to a previously
administered agent.
7. Subjects must not have received a donor lymphocyte infusion (DLI) within 8 weeks
prior to the first dose of study medication.
8. Subjects must not have a history of severe (grade 3-4) acute GVHD, and/or current
> grade 1 acute GHVD. Subjects must not have a history of chronic GVHD (whether
limited or extensive stage).
9. Subjects must not have autoimmune disease that has required systemic treatment in
the past 2 years (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment.
10. Subjects must not have a known history of congestive heart failure, unstable
angina pectoris, or cardiac arrhythmia (with the exception of chronic and
rate-controlled atrial fibrillation).
11. Subjects must not have a history of other serious underlying medical or
psychiatric condition that, in the opinion of the investigator, would impair the
ability to receive, tolerate and or comply with the planned treatment and
follow-up.
12. Subjects must not have a history of a known secondary primary malignancy that is
not in remission and/or that requires active therapy. Exceptions include
non-melanoma skin cancers and in situ cervical cancer that has undergone
curative-intent local therapy.
13. Subjects must not have a known active infection requiring intravenous antibiotic
therapy.
14. Subjects must not have a history of (non-infectious) pneumonitis that required
steroid treatment, evidence of interstitial lung disease, or active,
non-infectious pneumonitis. Subjects must not have active, non-infectious
colitis.
15. Subjects must not be pregnant or breastfeeding, or expecting to conceive or
father children within the projected duration of the trial, starting with the
screening visit through 120 days after the final dose of study medication.
16. Subjects must not have received a live vaccine within 30 days prior to the first
dose of study medication.
17. Subjects must not be or have an immediate family member (spouse, parent, legal
guardian, sibling or child) who is an investigational site sponsor or staff
directly involved with the trial, unless IRB approval is granted previously.
