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Daratumumab in Subjects With Relapsed/Refractory Acute Myelogenous Leukemia or High-Risk Myelodysplastic Syndrome

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Disease Information

Descriptive Information
Brief Title † Daratumumab in Subjects With Relapsed/Refractory Acute Myelogenous Leukemia or High-Risk Myelodysplastic Syndrome
Official Title † An Open-label, Phase 2 Trial Evaluating the Efficacy and Safety of Daratumumab in Subjects With Relapsed/Refractory Acute Myelogenous Leukemia or High-Risk Myelodysplastic Syndrome
Brief Summary The goal of this clinical research study is to learn if daratumumab can help to control acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS) that is refractory (does not respond to treatment) or relapsed (comes back after being treated). The safety of this drug will also be studied.
Detailed Description Study Drug Administration: Each cycle is 28 days (4 weeks). If you are found to be eligible to take part in this study, you will receive daratumumab by vein on Days 1, 8, 15, and 22 of Cycles 1 and 2, on Days 1 and 15 of Cycles 3-6, and then on Day 1 of Cycles 7 and beyond for up to 1 year or unless the disease stops responding to treatment, whichever is earlier. Your first dose will be given over about 4½ hours. After that, each infusion should take about 2½ hours. In this study, the following will be done to lower the chance of a daratumumab infusion related reaction: - You will get medications, including steroids, acetaminophen, and/or antihistamine before the infusion. If you are considered high risk, you may also get medications, including inhaled steroids, after the infusion. - The infusion may be slowed down or stopped if you have a reaction. - You may stay overnight in the hospital after the infusion so the study staff can check your health. You may ask the study staff for more information about the types of medications you will receive to lower your chance of an infusion-related reaction, including how they are administered and their risks. Length of Study: You may continue taking the study drug for up to 1 year. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Study Visits: If you can become pregnant, blood (about 1 teaspoon) will be drawn for a pregnancy test within 24 hours before your first dose of daratumumab. If the doctor thinks it is needed, you may have a physical exam at any of your study visits. On Day 1 of Cycles 1 and 2: - Blood (about 2 teaspoons) will be drawn for routine tests. - During Cycle 2 (+/- 2 days), you will have a bone marrow biopsy/aspirate to check the status of the disease. On Days 8, 15, and 22 of Cycles 1 and 2, blood (about 2 teaspoons) will be drawn for routine tests. On Day 1 of Cycles 3-6: - Blood (about 2 teaspoons) will be drawn for routine tests. - During Cycle 3, you will have an EKG. - If you can become pregnant, blood (about 1 teaspoon) will be drawn for a pregnancy test. On Day 1 of Cycles 3 and beyond (+/- 2 days), you will have a bone marrow aspirate/biopsy to check the status of the disease. You will continue to have these tests until you have a response to the study drug. The study doctor will decide if you will have this test. On Day 15 of Cycles 3-6, blood (about 2 teaspoons) will be drawn for routine tests. On Day 1 of Cycles 7 and beyond: - Blood (about 2 teaspoons) will be drawn for routine tests. - During Cycle 7 only, you will have an EKG. - If you can become pregnant, blood (about 1 teaspoon) will be drawn for a pregnancy test. End-of-Treatment Visit: About 28-35 days after your last dose of daratumumab: - You will have a physical exam. - Blood (about 2 teaspoons) will be drawn for routine tests. - You will have an EKG. - If the doctor thinks it is needed, you will have a bone marrow biopsy/aspiration. - If you can become pregnant, blood (about 1 teaspoon) will be drawn for a pregnancy test. Follow-Up Visits: The study staff will call you to ask how you are doing 1 time each month for the first year after your end-of-treatment visit, then every 6 months during the second year, and then 1 time every year after that. Each call should last about 5 minutes. If the disease has responded to treatment and the disease does not come back, blood (about 2 teaspoons) will be drawn for routine tests 1 time each month for the first 2 years after the end-of-treatment visit. You may have additional follow-up visits as part of your routine care. This will be discussed with you. This is an investigational study. Daratumumab is FDA approved and commercially available for treatment of multiple myeloma (MM). It is considered investigational to use it as treatment for AML or MDS. The study doctor can explain how the study drug is designed to work. Up to 36 patients will take part in this study. All will be enrolled at MD Anderson.
Study Phase Phase 2
Study Type † Interventional
Study Design †
Primary Outcome Measure † Overall Response (OR) of Daratumumab in Subjects With Relapsed/Refractory Acute Myelogenous Leukemia or High-Risk Myelodysplastic Syndrome
Secondary Outcome Measure † Adverse Events of Daratumumab in Subjects With Relapsed/Refractory Acute Myelogenous Leukemia or High-Risk Myelodysplastic Syndrome
Condition † Hematopoietic/Lymphoid Cancer Acute Myelogenous Leukemia High-Risk Myelodysplastic Syndrome
Intervention † DrugDaratumumab
Study Arms / Comparison Groups Daratumumab Participants receive Daratumumab by vein on Days 1, 8, 15, and 22 of Cycles 1 and 2, on Days 1 and 15 of Cycles 3-6, and then on Day 1 of Cycles 7 and beyond for up to 1 year or unless the disease stops responding to treatment, whichever is earlier.
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 36
Start Date † June 2017
Completion Date June 2021
Primary Completion Date June 2021
Eligibility Criteria † Inclusion Criteria: 1. Understand and voluntarily sign an informed consent form. 2. Age >/=18 years at the time of signing the informed consent form. 3. 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). 4. All non-hematological toxicity of previous cancer therapy should have resolved to = grade1 (except alopecia or other toxicities not involving major organs). 5. Eastern Cooperative Oncology Group (ECOG) performance status of = 2 at study entry. 6. Laboratory test results within these ranges: 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) 7. 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 (6 months after the last dose of daratumumab for women). 8. 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 6 months after receiving the last dose of study drug. 9. 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 µg/mL). Exclusion Criteria: 1. Pregnant or breast feeding females. 2. 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 7gm). 3. Subject has received daratumumab or other anti-CD38 therapies previously. 4. 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. 5. Subject has known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) 470 msec. 9. 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. 10. 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. 11. Exclude patients with known Kell antibodies.
Gender All
Ages 18 Years - N/A
Accepts Healthy Volunteers No
Contacts †† Gautam Borthakur, MBBS, 713-563-1586, CR_Study_Registration@mdanderson.org
Location Countries † United States
Administrative Information
NCT ID † NCT03067571
Organization ID 2016-0889
Secondary IDs ††
Responsible Party Sponsor
Study Sponsor † M.D. Anderson Cancer Center
Collaborators †† Janssen Scientific Affairs, LLC
Investigators † Principal Investigator: Gautam Borthakur, MBBS, M.D. Anderson Cancer Center
Information Provided By
Verification Date June 2017
First Received Date † February 24, 2017
Last Updated Date June 2, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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