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Daratumumab in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

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ClinicalTrials.gov Identifier: NCT03067571
Recruitment Status : Recruiting
First Posted : March 1, 2017
Last Update Posted : July 3, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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.

Condition or disease Intervention/treatment Phase
High Risk Myelodysplastic Syndrome Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia Biological: Daratumumab Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess response rate as determined by the International Working Group recommendations.

SECONDARY OBJECTIVES:

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.

EXPLORATORY OBJECTIVES:

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.

OUTLINE:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 27, 2017
Estimated Primary Completion Date : May 1, 2021
Estimated Study Completion Date : May 1, 2021


Arm Intervention/treatment
Experimental: Treatment (daratumumab)
Patients receive daratumumab 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.
Biological: Daratumumab
Given IV
Other Names:
  • Anti-CD38 Monoclonal Antibody
  • Darzalex
  • HuMax-CD38
  • JNJ-54767414




Primary Outcome Measures :
  1. Response rate as determined by the International Working Group recommendations [ Time Frame: Up to 3.5 years ]

Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 3.5 years ]
  2. Time on treatment [ Time Frame: Up to 3.5 years ]
  3. Overall survival [ Time Frame: Up to 3.5 years ]
  4. Progression free survival [ Time Frame: Up to 3.5 years ]
  5. Long-term response rate [ Time Frame: Up to 3.5 years ]

Other Outcome Measures:
  1. Biomarkers predictive of response or resistance to therapy [ Time Frame: Up to 3.5 years ]
    Will 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03067571


Contacts
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Contact: Gautam Borthakur 713-563-1586 gborthak@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Gautam Borthakur    713-563-1586      
Principal Investigator: Gautam Borthakur         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Gautam Borthakur M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03067571     History of Changes
Other Study ID Numbers: 2016-0889
NCI-2018-01222 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-0889 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: March 1, 2017    Key Record Dates
Last Update Posted: July 3, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Daratumumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs