Acute Myeloid Leukemia Clinical Trial
Daratumumab in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
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.
I. To assess response rate as determined by the International Working Group recommendations.
I. To assess safety and tolerability. II. To assess time on treatment. III. To assess overall survival. IV. To assess progression free survival. V. To assess long-term response rate.
I. To explore biomarkers predictive of response or resistance to therapy including expression of CD38 at study entry and at relapse and response rate based on CD38 expression level.
Patients receive daratumumab intravenously (IV) over 3.25-6.5 hours on days 1, 8, 15 and 22 of cycles 1-2, on days 1 and 15 of cycles 3-6, and on day 1 of subsequent cycles. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up monthly for 1 year, every 6 months for 1 year, and then annually thereafter.
Understand and voluntarily sign an informed consent form
Diagnosis of acute myeloid leukemia (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]). Myelodysplastic syndrome (MDS) will also be eligible. (Treatment approach for relapsed/refractory AML is very similar to that of high risk MDS)
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 >= 20 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)
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 human immunodeficiency virus (HIV) or hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg] or antibodies to hepatitis B surface and core antigens [anti-HBs and anti-HBc, respectively]) or hepatitis C (anti-hepatitis C virus [HCV] antibody positive or HCV-ribonucleic acid [RNA] quantitation positive)
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 (eg, 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
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There is 1 Location for this study
Houston Texas, 77030, United States
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