- Histologically or cytologically confirmed relapsed acute myeloid leukemia (AML) or
myelodysplastic syndrome (MDS), including any AML subtype, except acute promyelocytic
- Patients with minimal residual disease (MRD) positive relapse, as well as overt
hematologic/clinical relapse are eligible for the study (per IWG Response Criteria for
- Patients must have peripheral blast count ≤ 20,000/mm3. Use of hydroxyurea to control
blast count is permitted.
- Patients must be status post-1st allo-HCT (including: matched related, matched
unrelated, haploidentical, mismatched unrelated; and cord blood HCT).
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
- Adequate organ function, defined as:
- Hepatic transaminase (both alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) levels ≤2.5 times the institutional upper limit of normal
- Total bilirubin level ≤1.5 times the ULN (unless the patient has a history of
Gilbert's Syndrome, in which case, total bilirubin must be ≤2.5 times the ULN),
- Serum creatinine level ≤2.5 times the ULN or a calculated or measured creatinine
clearance of ≤30 ml/min, whichever is more stringent.
- Adequate organ reserve including cardiovascular (ejection fraction within
institutional normal limits), pulmonary (baseline pulmonary function test [PFT]:
carbon monoxide diffusion capacity in the lung [DLCO] > 50%, forced expiratory
volume in 1 second [FEV1] > 70%), renal, and hepatic functioning sufficient, in
the judgment of the Investigator, to undergo therapy.
- Normal thyroid function or stable thyroid tests on supplementation, except
euthyroid sick syndrome.
- Recovery from toxicities of clinical consequence attributed to previous chemotherapy
to CTCAE v4.0 Grade ≤ 1 (i.e., certain toxicities such as alopecia will not be
considered in this category).
- Female patients of childbearing potential must test negative for pregnancy at
enrollment and during the study. Sexually active women of child-bearing potential,
unless surgically sterile, must be willing to use a highly effective method of birth
control defined as those which result in a low failure rate (i.e., less than 1% per
year) such as implants, injectables, combined oral contraceptives, intra-uterine
devices (IUDs) or vasectomized partner. Male patients with partners of childbearing
potential must be either vasectomized or agree to use a condom in addition to having
their partners use another method of contraception resulting in a highly effective
method of birth control defined as those which result in a low failure rate (i.e.,
less than 1% per year) such as implants, injectables, combined oral contraceptives, or
IUDs. Patients should not have sexual intercourse with females who are either pregnant
or lactating without a condom. Contraception should be employed from the time of
consent through 12 weeks after MGD006 administration. Patients should also abstain
from sperm/egg donation during the course of the study.
- Able to have corticosteroids weaned to ≤0.5mg/kg prednisone/day (or equivalent)
- Able to have non-steroidal immunosuppression discontinued, including:
- mycophenolate (MMF)
- calcineurin inhibitors (tacrolimus, cyclosporine)
- JAK inhibitors (ruxolitinib)
- MTOR inhibitors (sirolimus)
- At least 18 years of age.
- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).
- Active GVHD, not controlled with corticosteroids ≤0.5mg/kg prednisone/day (or
- Currently receiving any other investigational agents.
- Any active untreated autoimmune disorders (with the exception of vitiligo, resolved
childhood atopic dermatitis, prior Grave's disease now euthyroid clinically and with
- Second primary malignancy that requires active therapy (adjuvant hormonal therapy is
- Antitumor therapy (chemotherapy, radiotherapy, antibody therapy, molecular- targeted
therapy, retinoid therapy, or investigational agent) within 14 days or 5 half-lives of
Cycle 1 Day 1, whichever is longer.
- At the time of study entry, steroids >0.5mg/kg of prednisone or equivalent (except
steroid inhaler, nasal spray or ophthalmic solution which are allowed).
- Use of immunosuppressant medications (other than steroids as noted) in the 2 weeks
prior to study drug administration (Cycle 1 Day 1).
- Isolated extramedullary relapse (i.e., no evidence of bone marrow involvement). As
noted above, patients with flow cytometry or molecular evidence of bone marrow MRD
will be allowed on the protocol.
- Known central nervous system (CNS) leukemia. Patients with suspected CNS leukemia must
be evaluated by lumbar puncture and be free of CNS disease prior to study entry.
Previously treated CNS leukemia is allowed provided adequate treatment has been
provided and the patient is free of CNS disease.
- Any medical or psychiatric condition limiting full compliance or increasing the safety
risk, at the discretion of the PI, such as:
- active uncontrolled infection (including, but not limited to viral, bacterial,
fungal, or mycobacterial infection),
- known human immunodeficiency virus infection,
- known, active, or chronic hepatitis B or C infection (appropriately treated
HBV/HCV infections with documented clearance of viral titer are allowed),
- Grade 3 or 4 bleeding,
- significant pulmonary compromise including the requirement for supplemental
oxygen, history of non-infectious pneumonitis (including radiation pneumonitis),
pulmonary fibrosis, or severe chronic obstructive pulmonary disease (COPD),
- uncontrolled (persistent) hypertension (systolic pressure > 180 mm Hg or
diastolic pressure > 100 mm Hg
- clinically significant arrhythmia, clinically significant baseline QTcF >480
- unstable angina,
- recent myocardial infarction within 6 months prior to study drug administration
(Cycle 1 Day 1),
- clinically significant heart disease, such as, congestive heart failure, history
of pericarditis, myocarditis,
- history of stroke or transient ischemic event within 3 months prior to study drug
administration (Cycle 1 Day 1),
- untreated pulmonary embolism, or non-catheter-related deep-vein thrombosis in the
3 months prior to study drug administration (Cycle 1 Day 1),
- pregnancy, or breast feeding,
- major surgery or trauma within 4 weeks before enrollment.
- Known hypersensitivity to murine, yeast, or recombinant proteins; polysorbate 80;
recombinant human serum albumin; benzyl alcohol; or any excipient contained in the
MGD006 drug formulation.
- Dementia or altered mental status that would preclude sufficient understanding to
provide informed consent.