A Clinical Study of Cusatuzumab Plus Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia who are not Candidates for Intensive Chemotherapy
- Conditions
- Acute Myeloid LeukemiaMedDRA version: 21.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-000473-23-IT
- Lead Sponsor
- JANSSEN CILAG INTERNATIONAL NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 150
1. =18 years of age
MODIFIED
2.1. AML according to WHO 2016 criteria and fulfilling all of the following criteria that defines those who are not candidates for intensive chemotherapy:d procedures required for, the study and is willing to participate in the study
¿ =75 years of age or
¿ <75 years of age with of at least one of the following comorbidities:
o Eastern Cooperative Oncology Group (ECOG) Performance Status of 2
o Severe cardiac comorbidity defined as congestive heart failure or ejection fraction =50%
o Severe pulmonary comorbidity defined as documented pulmonary disease with lung diffusing capacity for carbon monoxide (DLCO) =65%
of expected, or forced expiratory volume in 1 second (FEV1) =65% of expected or dyspnea at rest requiring oxygen
o Moderate hepatic impairment defined according to National Cancer Institute (NCI) organ dysfunction classification criteria (total bilirubin = 1.5 up to 3 times upper limit of normal [ULN])
o Creatinine clearance <45 mL/ min/1.73 m² (by MDRD formula)
o Comorbidity that, in the Investigator's opinion, makes the patient unsuitable for intensive chemotherapy and must be documented and approved by the Sponsor before randomization
MODIFIED
3.1. De novo or secondary AML
MODIFIED
4.1. Previously untreated AML (except: emergency leukapheresis, hydroxyurea, and/or 1 dose of cytarabine [eg, 1-2g/m^2] during the screening phase to control hyperleukocytosis. These treatments must be discontinued =24 hours prior to start of study drug). Empiric all trans retinoic acid (ATRA) treatment for presumed acute promyelocytic leukemia (APL) is permitted but APL must be ruled out and ATRA must be discontinued =24 hours prior to the start of study drug;
MODIFIED
5.1. Not eligible for an allogeneic hematopoietic stem cell transplantation.
MODIFIED
6.1. ECOG Performance Status score of 0, 1 or 2.
MODIFIED
7.1. The following clinical laboratory values at screening:
¿ AST or ALT <3 times ULN; for participants with leukemic infiltration of the liver, AST and ALT <5 times ULN is permitted
¿ Total bilirubin = 3 times ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin or in case of liver infiltration by AML
(documented by biopsy or imaging) serum total bilirubin <5 times ULN
¿ Creatinine Clearance >30 mL/min (by MDRD formula)
MODIFIED
8.1. A woman must be either:
¿ Not of childbearing potential: postmenopausal (amenorrhea for at least 12 months);
¿ Of childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for participants in the clinical study while receiving study treatment and for at least 3 months after the last dose of study treatment A woman of childbearing potential must have a negative highly-sensitive serum ß-hCG or urine pregnancy test at screening.
A woman of childbearing potential must agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study treatment and for 3 months after the last dose of study treatment.
MODIFIED
9.1. 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 for at least 3 months after last study treatment.
¿ Must agree to not donate sperm during the
Any potential participant who meets any of the following criteria will be excluded from participating in the study:
1. Criterion modified per Amendment 1
1.1. Acute promyelocytic leukemia
2. Leukemic involvement or clinical symptoms of leukemic involvement of the central nervous system.
3. Criterion modified per Amendment 1
3.1. Use of immune suppressive agents for the past 4 weeks before the first administration of cusatuzumab on Cycle 1 Day 3. For regular use of
systemic corticosteroids, participants may only be included if free of systemic corticosteroids for a minimum of 5 days before the first administration of cusatuzumab. Treatment of adrenal insufficiency with physiologic replacement doses of corticosteroids are allowed.
4. Prior treatment with a hypomethylating agent for treatment of AML or MDS
5. Criterion modified per Amendment 1
5.1. Active malignancies (ie, progressing or requiring treatment in the last 24 months) other than the disease being treated under study. The only allowed exceptions are:
¿ Non-melanoma skin cancer treated within the last 24 months that is considered completely cured
¿ Adequately treated breast lobular carcinoma in situ and breast ductal carcinoma in situ
¿ Adequately treated cervical carcinoma in situ without evidence of disease
¿ History of localized breast cancer and receiving antihormonal agents, or history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy
¿ Malignancy that is considered cured with minimal risk of recurrence
6. Criterion modified per Amendment 1
6.1. Any active systemic infection
7. Criterion modified per Amendment 1
7.1. A history of human immunodeficiency virus (HIV) antibody positive or tests positive for HIV at screening
8. Criterion modified per Amendment 1
8.1. Active hepatitis B or C infection or other clinically active liver disease Seropositive for hepatitis B: defined by a positive test for hepatitis B
surface antigen [HBsAg]. Participants with resolved infection (ie, participants who are HBsAg negative with antibodies to total hepatitis B core antigen [anti-HBc] with or without the presence of hepatitis B surface antibody [anti-HBs]) must be screened using real-time polymerase chain reaction (RT-PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are RT-PCR positive will be excluded. Participants 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 RT-PCR.
Known Hepatitis C infection or positive serologic testing for Hepatitis C (anti-HCV antibody)
9. New York Heart Association Class IV heart failure or ongoing unstablE angina
10. Known allergies, hypersensitivity, or intolerance to cusatuzumab or azacitidine or its excipients (ie, mannitol, an excipient of azacitidine).
11. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or physical limitations that could prevent, limit, or confound the protocol-specified assessments.
12. Criterion modified per Amendment 1
12.1. Major surgery, (eg, requiring general anesthesia) within 4 weeks prior to initiation of the study.
13. Women who are breastfeeding.
14. Received a live, attenuated vaccine within 4 weeks prior to initiation of study treatment.
NOTE: Investigators should ensure that all study enrollment (inclusion/exclusion) criteria have
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method