Clinical Trials /

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

Description:

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).

Related Conditions:
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
  • Secondary Myelodysplastic Syndrome
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: CR108734
  • SECONDARY ID: 2019-003576-40
  • SECONDARY ID: 74494550MDS2001
  • NCT ID: NCT04264806

Conditions

  • Myelodysplastic Syndromes
  • Leukemia, Myelomonocytic, Chronic

Interventions

DrugSynonymsArms
AzacitidineAzacitidine and Cusatuzumab: Participants with MDS or CMML
CusatuzumabJNJ-74494550,, ARGX-110Azacitidine and Cusatuzumab: Participants with MDS or CMML

Purpose

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).

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Azacitidine: Participants with MDS or CMMLExperimentalParticipants 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.
  • Azacitidine
Azacitidine and Cusatuzumab: Participants with MDS or CMMLExperimentalParticipants 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.
  • Azacitidine
  • Cusatuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of de novo or secondary higher-risk Myelodysplastic Syndrome (MDS) or
             Chronic Myelomonocytic Leukemia (CMML) per World Health Organization (WHO) 2016
             criteria

          -  At study entry, higher-risk MDS (intermediate, high, and very high risk MDS per
             Revised International Prognostic Scoring System [IPSS R]) OR higher-risk CMML
             (intermediate-2 or high risk CMML per CMML-specific Prognostic Scoring System
             [CPSS-Mol]). Participants with previous lower-risk MDS or CMML that has evolved to
             higher-risk MDS or CMML are eligible

          -  At study entry, not a candidate for Hematopoietic Stem Cell Transplantation (HSCT)

          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

          -  Adequate liver and renal function defined as follows: Aspartate aminotransferase (AST)
             or alanine aminotransferase (ALT) less than (<) 3 * upper limit of normal (ULN); Total
             bilirubin less than or equal to (<=) 1.5 * ULN, unless bilirubin rise is due to
             Gilbert's syndrome or of non hepatic origin; and Creatinine clearance (CrCl) greater
             than (>) 30 milliliter per minute per 1.73 square meters (mL/min/1.73 m^2) (by
             Modification of Diet in Renal Disease formula)

        Exclusion Criteria:

          -  Received prior HSCT or any prior treatment, including hypomethylating agent (HMAs),
             for higher-risk MDS or CMML. Prior supportive therapies including transfusion and
             growth factors are acceptable

          -  Received prior treatment with cusatuzumab

          -  Presence of the breakpoint cluster region protein-Abelson murine leukemia (bcr-abl)
             rearrangement

          -  Received a live, attenuated vaccine within 4 weeks prior to initiation of study drug

          -  Any active systemic infection
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:Up to 4 years
Safety Issue:
Description:ORR is a composite of complete remission (CR), partial remission (PR) and marrow complete remission (mCR) as per modified International Working Group (IWG) criteria.

Secondary Outcome Measures

Measure:Percentage of Participants Achieving Complete Remission (CR) and Partial Remission (PR)
Time Frame:Up to 4 years
Safety Issue:
Description:Percentage of participants achieving CR and PR as per IWG criteria will be reported.
Measure:Percentage of Participants Achieving Complete Remission (CR)
Time Frame:Up to 4 years
Safety Issue:
Description:Percentage of participants achieving CR as per IWG criteria will be reported.
Measure:Time to response
Time Frame:Up to 4 years
Safety Issue:
Description: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.
Measure:Duration of response
Time Frame:Up to 4 years
Safety Issue:
Description:Time from achieving the first response of CR, PR, or mCR to relapse or death from any cause for those participants who responded.
Measure:Percentage of Participants who Achieve Transfusion Independence
Time Frame:Up to 4 years
Safety Issue:
Description: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.
Measure:Time to Transformation of Participants to Acute Myeloid Leukemia (AML)
Time Frame:Up to 4 years
Safety Issue:
Description:Time to transformation of participants to AML will be reported. Transformation to AML is defined as >= 20% bone marrow blasts.
Measure:Progression Free Survival (PFS)
Time Frame:Up to 4 years
Safety Issue:
Description:PFS is defined as the time from randomization to disease progression; relapse from CR, PR, or mCR; or death from any cause.
Measure:Overall Survival (OS)
Time Frame:Up to 4 years
Safety Issue:
Description:OS is defined as the time from randomization to death.
Measure:Hematologic Improvement Rate
Time Frame:Up to 4 years
Safety Issue:
Description: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.
Measure:Percentage of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
Time Frame:Up to 4 years
Safety Issue:
Description: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.
Measure:Percentage of Participants With Clinically Significant Abnormalities in Laboratory Parameters
Time Frame:Up to 4 years
Safety Issue:
Description:Percentage of participants with clinically significant abnormalities in laboratory parameters will be reported.
Measure:Percentage of Participants With Clinically Meaningful Improvement in Functional Assessment of Cancer Therapy - Anemia Trial Outcome Index (FACT-An TOI) Total Score
Time Frame:Up to 4 years
Safety Issue:
Description: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.
Measure:Area Under the Serum Concentration-Time Curve Within Timespan t1 to t2 (AUC[t1-t2]) of Cusatuzumab
Time Frame:Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
Safety Issue:
Description:The AUC(t1-t2) is the area under the serum concentration-time curve within timespan t1 to t2.
Measure:Maximum Serum Concentration (Cmax) of Cusatuzumab
Time Frame:Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
Safety Issue:
Description:Cmax is the maximum observed serum concentration.
Measure:Minimum Serum Concentration (Cmin) of Cusatuzumab
Time Frame:Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
Safety Issue:
Description:Cmin is the minimum observed serum concentration.
Measure:Elimination Half-Life (t1/2) of Cusatuzumab
Time Frame:Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
Safety Issue:
Description: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).
Measure:Systemic Clearance (CL) of Cusatuzumab
Time Frame:Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
Safety Issue:
Description:CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Measure:Volume of Distribution (Vz) of Cusatuzumab
Time Frame:Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
Safety Issue:
Description: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.
Measure:Number of Participants with Developed Antidrug Antibodies to Cusatuzumab
Time Frame:Cycle 1: Day 3 (Predose); Cycle 1: Day 17 (Predose); Cycle 2: Day 3 (Predose); Cycle 8 and 11: Day 3 (Predose) and EOT (up to 4 years)
Safety Issue:
Description:Venous blood samples are analyzed for presence of antidrug antibodies to cusatuzumab. Participants with titer of confirmed positive samples for cusatuzumab antibodies are reported.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

February 12, 2020