Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Acute Graft Versus Host Disease

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Venetoclax

Azacitidine

Immunoglobulins

Antimetabolites

Enzyme Inhibitors

Cusatuzumab 20 mg/kg administered intravenously on days 3 and 17 in combination with venetoclax administered orally up to 400 mg once daily and azacitidine 75 mg/m\^2 administered subcutaneously or intravenously once daily for 7 days of a 28 day cycle

Venetoclax administered orally up to 400 mg once daily and azacitidine 75 mg/m\^2 administered subcutaneously or intravenously once daily for 7 days of a 28 day cycle

Cusatuzumab

The goal of this clinical trial is to learn if participants treated with the experimental drug cusatuzumab added to venetoclax and azacitidine works to treat acute myeloid leukemia (AML) compared to venetoclax and azacitidine. Venetoclax and azacitidine are drugs commonly used to treat AML in patients that are unable to receive chemotherapy to treat AML. The main question the clinical trial aims to answer is does cusatuzumab added to venetoclax and azacitidine prolong the length of time participants live compared to venetoclax and azacitidine?

This is a randomized, open-label, multicenter, Phase 2 trial to evaluate the efficacy, safety, and pharmacodynamics of cusatuzumab in combination with venetoclax and azacitidine compared to venetoclax and azacitidine in persons with newly diagnosed AML who are deemed ineligible for intensive chemotherapy.

Potential participants will be considered ineligible for intensive chemotherapy and, therefore, eligible for the study, if they meet the trial eligibility criteria. Potential participants will undergo a diagnostic bone marrow biopsy and aspirate collected for pathology review, cytogenetics, fluorescence in situ hybridization (FISH), and polymerase chain reaction (PCR) analysis and other studies for confirmation of a diagnosis of AML and to define whether participants have adverse, intermediate, or favorable AML risk features.

The enrolled trial population will be enriched for participants with adverse risk features by enrolling adverse, intermediate, and favorable risk participants at a ratio of 3:1:1, respectively (i.e., 72 adverse risk, 24 intermediate risk, and 24 favorable risk participants will be enrolled). Enrolled participants will then be randomized 2:1 to either the experimental arm or the active comparator arm.

A Study Comparing Venetoclax and Azacitidine Plus Cusatuzumab to Venetoclax and Azacitidine in Newly Diagnosed AML Ineligible for Intensive Therapy

Multicenter, Open-label, Randomized, Phase 2 Study of Venetoclax and Azacitidine Plus Cusatuzumab Versus Venetoclax and Azacitidine Alone in Newly Diagnosed AML Patients Who Are Not Candidates for Intensive Therapy

Proportion of participants achieving CR per the European LeukemiaNet (ELN) 2022 criteria

Sum of CR+CRh+CRi rate. CRh is defined as CR with partial hematologic recovery. CRi is defined as CR with incomplete hematologic recovery. Defined per ELN 2022 criteria.

Defined per ELN 2022 criteria and guidelines for testing

In subgroups of participants according to specified AML risk stratification models. CR defined per ELN 2022 criteria.

OncoVerity, Inc.

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Participants will receive azacitidine 75 milligram per meter square (mg/m\^2) subcutaneously (SC) or intravenously (IV) on Day 1 through Day 7 and cusatuzumab 10 milligram per kilogram (mg/kg) IV on Day 3 and Day 17 of each 28-day cycle in Part 1. Part 1 findings will be reviewed by a data review committee.

Participants will receive azacitidine 75 mg/m\^2 SC or IV on Day 1 through Day 7 and cusatuzumab 20 mg/kg IV on Day 3 and Day 17 of each 28-day cycle in Part 1. Part 1 findings will be reviewed by a data review committee.

Azacitidine SC or IV will be administered at a standard dose of 75 mg/m\^2 on days 1-7 of each cycle.

Cusatuzumab IV will be administered as 10 mg/kg or 20 mg/kg on days 3 and 17 of each cycle.

Clayton Smith, MD

The purpose of this study is to determine the efficacy of cusatuzumab in combination with azacitidine in participants with previously untreated acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy.

AML is a heterogeneous disease characterized by uncontrolled clonal expansion of hematopoietic progenitor cells. As the most common form of acute leukemia, AML accounts for the largest number of annual deaths from leukemia. Over 95 percent (%) of AML blasts harvested from newly diagnosed AML participants expressed Cluster of Differentiation (CD) 70 on the cell surface. Cusatuzumab (JNJ-74494550) is a humanized monoclonal antibody of camelid origin, binding with tight affinity to human CD70. Cusatuzumab has been modified to induce enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) for therapeutic use in participants with cancer. Azacitidine is a pyrimidine nucleoside analogue of cytidine with antineoplastic activity and is indicated for the treatment of adult participants with AML or intermediate 2 and high-risk myelodysplastic syndrome (MDS) with greater than 20% marrow blasts who are not eligible for hematopoietic stem cell transplantation. This study will evaluate 2 doses of cusatuzumab in combination with standard dose azacitidine in participants with AML who are not candidates for intensive chemotherapy (Part 1). Part 1 data will be reviewed by a Data Review Committee to select a preferred dose of cusatuzumab. The study will include a Screening Phase (28 days prior to randomization), a Treatment Phase, and a Follow-up Phase. The study includes evaluations like vital signs, electrocardiogram, spirometry test, serum chemistry and hematology tests.

A Study of Cusatuzumab Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy

A Phase 2 Study of Cusatuzumab Plus Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy

Percentage of participants with complete response based on European Leukemia Network (ELN) 2017 response criteria assessment will be reported.

Percentage of participants with CRh will be reported based on ELN 2017 response criteria assessment.

Percentage of participants with CR plus CRh will be reported based on ELN 2017 response criteria assessment.

Percentage of participants with CRi will be reported based on ELN 2017 response criteria assessment.

ORR is defined as percentage of participants with CR, CRh and CRi based on ELN 2017 response criteria assessment.

Percentage of participants with CR without minimal residual disease (MRD) will be reported and is defined as less than 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level \<10\^-3; determined by central lab).

Percentage of participants with negative MRD who achieved CR, CRh, CRi, or MLFS will be reported and is defined as less than (\<) 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level \<10\^-3).

Time to response, defined as time from randomization in Part 1 to achieving the first response of CR, CRh, or CRi.

Duration of response is defined as time from achieving the first response of CR, CRh, or CRi to disease relapse or death from any cause.

Transfusion independence (RBC or platelets) is defined as a period of at least 56 consecutive days with no transfusion between first dose of study drug and the last dose of study drug +30 days.

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.

Cmin is the minimum observed serum concentration.

Cmax is the maximum observed serum concentration.

Number of participants exhibiting anti-drug antibodies for cusatuzumab alone and in combination with azacitidine will be reported.

argenx

Janssen Research & Development, LLC

Symptoms and General Pathology

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Precancerous Conditions

Participants with acute myeloid leukemia (AML) will receive cusatuzumab intravenously (IV) in combination with azacitidine subcutaneously (SC) or IV. The dose levels will be escalated based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified.

Participants with acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) will receive cusatuzumab intravenously (IV) at the recommended Phase 2 dose (RP2D) determined in Part 1 in combination with azacitidine subcutaneously (SC) or IV.

Cusatuzumab at a dose 20 milligram per kilogram (mg/kg) once every 2 weeks will be administered intravenously.

Azacitidine at a dose 75 milligram per square meters (mg/m\^2) will be administered subcutaneously or intravenously.

Janssen Pharmaceutical K.K., Japan Clinical Trial

The purpose of this study is to determine the recommended Phase 2 dose and evaluate safety profile of cusatuzumab in combination with azacitidine in Japanese participants with treatment naïve acute myeloid leukemia (AML) who are not candidates for intensive treatment.

A Study of Cusatuzumab Plus Azacitidine in Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome Who Are Not Candidates for Intensive Treatment

A Phase 1 Study of Cusatuzumab Plus Azacitidine in Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome Who Are Not Candidates for Intensive Treatment

Number of participants with AEs and SAEs will be reported.

Number of participants with DLTs will be reported.

Severity of DLT as assessed by NCI-CTCAE in participants will be reported.

Percentage of participants with complete response based on response criteria per investigator assessment in participants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) will be reported.

ORR is defined as percentage of participants with CR, CRh and CRi based on response criteria per investigator assessment in participants with AML.

ORR is defined as the percentage of participants with CR, partial response (PR) and marrow CR based on response criteria per investigator assessment in participants with MDS.

Percentage of participants with hematologic improvement will be reported according to response criteria per investigator assessment in participants with MDS.

Time to response is defined as time from first dose to achieving the first response of CR, CRh, or CRi in participants with AML and CR, PR or marrow CR in participants with MDS..

Duration of response is defined as time from achieving the first response of CR, CRh, or CRi in participants with AML and CR, PR or marrow CR in participants with MDS to hematologic relapse or death of any cause.

OS is defined as the time from initial study intervention administration to death from any cause.

Ctrough is the serum concentration immediately prior to the next drug administration.

Janssen Pharmaceutical K.K.

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Myeloproliferative Disorders

Myelodysplastic-Myeloproliferative Diseases

Chronic Disease

Disease Attributes

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Participants with higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) will receive azacitidine 75 milligram per meter square (mg/m\^2) body surface area (BSA) subcutaneously or Intravenously per local label on Days 1 through Day 7 of each 28-day cycle. Participants will be treated until disease progression; relapse from complete remission (CR), partial remission (PR), or marrow complete remission (mCR); transformation to acute myeloid leukemia (AML); death; or unacceptable toxicity.

Participants with higher-risk MDS or CMML will receive azacitidine 75 mg/m\^2 BSA subcutaneously or Intravenously per local label on Days 1 through 7 and cusatuzumab 20 mg/kg IV on Days 3 and 17 of each 28-day cycle. Participants will be treated until disease progression; relapse from CR, PR, mCR; transformation to AML; death; or unacceptable toxicity.

Participants will receive subcutaneous (SC) or intravenous (IV) injection of Azacitidine 75 mg/m\^2.

Participants will receive SC or IV injection of Cusatuzumab 20 mg/kg.

Janssen Research & Development, LLC Clinical trials

The purpose of the study is to compare overall response rate (ORR) between treatment groups in participants with higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) who are not eligible for Hematopoietic Stem Cell Transplantation (HSCT).

Cusatuzumab (also known as JNJ-74494550 and ARGX-110) is a humanized monoclonal antibody of camelid origin that binds with high affinity to human Cluster of Differentiation 70 (CD70). Azacitidine (an Hypomethylating agent \[HMA\]) is approved for the treatment of higher-risk MDS in the United States (US) and the European Union (EU). Both approvals are based on data showing decreased transfusion burden, delayed progression to acute myeloid leukemia (AML), improved quality of life, and extended survival. It is hypothesized that the addition of cusatuzumab to azacitidine will result in an improvement in overall response rate (ORR) compared with azacitidine alone in participants with higher-risk MDS or CMML.

A Study of Cusatuzumab in Combination With Azacitidine Compared With Azacitidine Alone in Patients With Higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) and Who Are Not Candidates for Hematopoietic Stem Cell Transplantation (HSCT)

A Phase 2, Randomized, Open-label Study of Cusatuzumab in Combination With Azacitidine Compared With Azacitidine Alone in Patients With Higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) and Who Are Not Candidates for Hematopoietic Stem Cell Transplantation (HSCT)

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

ORR is a composite of complete remission (CR), partial remission (PR) and marrow complete remission (mCR) as per modified International Working Group (IWG) criteria.

Percentage of participants achieving CR as per IWG criteria will be reported.

Percentage of participants who achieve transfusion independence will be reported. Transfusion independence is defined as a period of greater than or equal to (\>=) 56 consecutive days with no transfusion occurring between the first and last dose of study drug +30 days.

Time to transformation of participants to AML will be reported. Transformation to AML is defined as \>= 20% bone marrow blasts.

PFS is defined as the time from randomization to disease progression; relapse from CR, PR, or mCR; or death from any cause.

OS is defined as the time from randomization to death.

Hematologic improvement rate is defined as erythroid response (pretreatment, less than (\<) 11 g/dL; hemoglobin \>= 1.5 g/dL; relevant reduction of units of RBC transfusions by an absolute number of \>= 4 Red blood cell (RBC) transfusions/8 weeks compared with the pretreatment transfusion number in the previous 8 weeks. Only RBC transfusions given for a hemoglobin of \<= 9.0 g/dL pretreatment will count in the RBC transfusion response evaluation; platelet response (pretreatment \<100\*10\^9/L); absolute increase of \>= 30\*109/L for participants starting with \>20\*10\^9/L platelets; increase to \>20\*109/L and by \>= 100% for participants starting with \<= 20\*109/L platelets; Neutrophil response (pretreatment \<1.0×10\^9/L); and at least 100% increase and an absolute increase of \>0.5\*10\^9/L.

An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

Percentage of participants with clinically significant abnormalities in laboratory parameters will be reported.

The AUC(t1-t2) is the area under the serum concentration-time curve within timespan t1 to t2.

T1/2 is the time measured for the serum concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).

CL is a quantitative measure of the rate at which a drug substance is removed from the body.

The Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.

Venous blood samples are analyzed for presence of antidrug antibodies to cusatuzumab. Participants with titer of confirmed positive samples for cusatuzumab antibodies are reported.

Percentage of participants achieving CR and PR as per IWG criteria will be reported.

Time to response for participants who achieved CR, PR and mCR responses, defined as time from randomization to achieving the first response of CR, PR, or mCR as per modified IWG criteria.

Time from achieving the first response of CR, PR, or mCR to relapse or death from any cause for those participants who responded.

FACT-An is a scale in Functional Assessment of Chronic Illness Therapy Measurement System. It consists of Functional Assessment of Cancer Therapy (general version; FACT-G) and 20 questions labeled "additional concerns" that measure anemia/fatigue. FACT-G is 27-item compilation of general questions divided into 4 primary quality of life domains: physical well-being, social/family well-being, emotional wellbeing, and functional well-being. Participants will be asked to rate scale items as it applies to past 7 days, on 5-point scale (0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much). Negatively stated items will be reversed by subtracting the response from 4. After reversing the proper items, items are summed to a total to generate a score on (sub)scale. A summary Trial Outcome Index total score (FACT An TOI) will be calculated by summing physical well being, functional well being, and anemia symptoms subscales and higher is the score better is the quality of life.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study Comparing Venetoclax and Azacitidine Plus Cusatuzumab to Venetoclax and Azacitidine in Newly Diagnosed AML Ineligible for Intensive Therapy	NCT06384261	Leukemia, Myelo...	Cusatuzumab Venetoclax Azacitidine	18 Years -	OncoVerity, Inc.
A Study Comparing Venetoclax and Azacitidine Plus Cusatuzumab to Venetoclax and Azacitidine in Newly Diagnosed AML Ineligible for Intensive Therapy	NCT06384261	Leukemia, Myelo...	Cusatuzumab Venetoclax Azacitidine	18 Years -	OncoVerity, Inc.
A Study of Cusatuzumab Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy	NCT04023526	Leukemia, Myelo...	Azacitidine Cusatuzumab	18 Years -	OncoVerity, Inc.
A Study of Cusatuzumab Plus Azacitidine in Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome Who Are Not Candidates for Intensive Treatment	NCT04241549	Leukemia, Myelo...	Cusatuzumab Azacitidine	20 Years -	OncoVerity, Inc.
A Study of Cusatuzumab Plus Azacitidine in Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome Who Are Not Candidates for Intensive Treatment	NCT04241549	Leukemia, Myelo...	Cusatuzumab Azacitidine	20 Years -	OncoVerity, Inc.
A Study of Cusatuzumab in Combination With Azacitidine Compared With Azacitidine Alone in Patients With Higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) and Who Are Not Candidates for Hematopoietic Stem Cell Transplantation (HSCT)	NCT04264806	Myelodysplastic... Leukemia, Myelo...	Azacitidine Cusatuzumab	18 Years -	Janssen Research & Development, LLC

Spots Global Cancer Trial Database for cusatuzumab

Every month we try and update this database with for cusatuzumab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cusatuzumab

Every month we try and update this database with for cusatuzumab cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cusatuzumab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.