Daratumumab in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Condition: High Risk Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: Daratumumab
Intervention description: Given IV
Intervention MeSH terms: Daratumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well daratumumab works in treating patients with acute
      myeloid leukemia that has come back or does not respond to treatment or high-risk
      myelodysplastic syndrome. Immunotherapy with monoclonal antibodies, such as daratumumab, may
      help the body's immune system attack the cancer, and may interfere with the ability of tumor
      cells to grow and spread.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Understand and voluntarily sign an informed consent form

          -  Age >/=18 years at the time of signing the informed consent form

          -  Diagnosis of AML [other than acute promyelocytic leukemia (APL)] with
             refractory/relapsed disease; patients with relapsed/refractory high-risk
             [(intermediate-2 or higher by International Prognostic Scoring System (IPSS) and/or
             >/= 10% blasts)] MDS will also be eligible. (Treatment approach for
             relapsed/refractory AML is very similar to that of high risk MDS), or diagnosis of
             relapsed/refractory T-ALL/T-LBL.

          -  All non-hematological toxicity of previous cancer therapy should have resolved to =<
             grade 1 (except alopecia or other toxicities not involving major organs)

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry

          -  Serum creatinine </= 2 mg/dL and estimated glomerular filtration rate or creatinine
             clearance >/= 40 ml/min

          -  Total bilirubin =< 2 mg/dL

          -  Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x upper
             limit of normal (ULN)

          -  Women of childbearing potential must be practicing a highly effective method of birth
             control consistent with local regulations regarding the use of birth control methods
             for subjects participating in clinical studies: eg, established use of oral, injected
             or implanted hormonal methods of contraception; placement of an intrauterine device or
             intrauterine system; barrier methods: condom with spermicidal
             foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps)
             with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the
             vasectomized partner should be the sole partner for that subject); true abstinence
             (when this is in line with the preferred and usual lifestyle of the subject) during
             and after the study (3 months after the last dose of daratumumab for women)

          -  A man who is sexually active with a woman of childbearing potential and has not had a
             vasectomy must agree to use a barrier method of birth control eg, either condom with
             spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm
             or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men
             must also not donate sperm during the study and for 3 months after receiving the last
             dose of study drug

          -  AML relapse > 6 months since autologous or allogeneic stem cell transplantation,
             provided there is no active graft-versus-host disease (GVHD) > grade 1; no treatment
             with high dose steroids for GVHD (up to 20 mg prednisolone or equivalent); no
             treatment with immunosuppressive drugs with the exception of low dose cyclosporine and
             tacrolimus (blood levels of 0.5-0.6 ug/mL)

        Exclusion Criteria:

          -  White blood cell count more than 25 × 109 /L prior to initiation of venetoclax

          -  Pregnant or breast feeding females

          -  Cancer chemotherapy within 2 weeks prior to start of daratumumab treatment (exception
             hydroxyurea). Use of hydroxyurea to control proliferative disease will be allowed
             prior to starting therapy on study and for 7 days during cycle 1-3 (maximum daily dose
             of 7 gm)

          -  Subject has received daratumumab or other anti-CD38 therapies previously

          -  Subject has received a cumulative dose of corticosteroids more than the equivalent of
             >= 140 mg of prednisone within the 2 week period before cycle 1, day 1

          -  Subject has known chronic obstructive pulmonary disease (COPD) with a forced
             expiratory volume in 1 second (FEV1) < 50% of predicted normal. NOTE: FEV1 testing is
             required for patients suspected of having COPD and subjects must be excluded if FEV1 <
             50% of predicted normal

          -  Subject has a history of another malignancy within 5 years before cycle 1, day 1
             (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ
             of the cervix, or malignancy that in the opinion of the investigator, with concurrence
             with the IND office and supporter's medical monitor, is considered cured with minimal
             risk of recurrence)

          -  Subject is known to be seropositive for hepatitis B (defined by a positive test for
             hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects
             who are HBsAg negative but positive for antibodies to hepatitis B core antigen
             [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti- HBs]) must be
             screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B
             virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION:
             Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as
             the only serologic marker) AND a known history of prior HBV vaccination, do not need
             to be tested for HBV DNA by PCR

          -  Subjects who are seropositive for hepatitis C (except in the setting of a sustained
             virologic response [SVR], defined as aviremia at least 12 weeks after completion of
             antiviral therapy) will be excluded.

          -  Subject has clinically significant cardiac disease, including: myocardial infarction
             within 1 year before Cycle 1, Day 1, or unstable or uncontrolled disease/condition
             related to or affecting cardiac function (e.g., unstable angina, congestive heart
             failure, New York Heart Association Class III-IV); cardiac arrhythmia (Common
             Terminology Criteria for Adverse Events [CTCAE] version 4.03 grade 2 or higher) or
             clinically significant electrocardiogram (ECG) abnormalities; screening 12-lead ECG
             showing a baseline QT interval as corrected by Fridericia's formula (QTcF) > 470 msec

          -  Subject has known severe allergies, hypersensitivity, or intolerance to monoclonal
             antibodies or human proteins, or their excipients (refer to the latest version of the
             Investigator Brochure), or known sensitivity to mammalian-derived products

          -  Subject has any concurrent medical condition or disease (eg, active systemic
             infection, laboratory abnormalities) that is likely to interfere with study procedures
             or results, or that in the opinion of the investigator would constitute a hazard for
             participating in this study

          -  Exclude patients with known Kell antibodies