Clinical Trials /

A Study of JNJ-67571244 in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

NCT03915379

Description:

The main purpose of this study are to determine the recommended Phase 2 dose(s) (RP2D) route of administration, schedule and the maximum tolerated dose (MTD) in Part 1 and to determine the safety and tolerability of JNJ-67571244 at the RP2D regimen(s) and to evaluate the preliminary clinical activity of JNJ-67571244 in Part 2.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of JNJ-67571244 in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)
  • Official Title: A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of JNJ-67371244 (Bispecific Antibody Targeting CD33 and CD3), in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

Clinical Trial IDs

  • ORG STUDY ID: CR108582
  • SECONDARY ID: 2018-004452-37
  • SECONDARY ID: 67571244AML1001
  • NCT ID: NCT03915379

Conditions

  • Leukemia, Myeloid, Acute
  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
JNJ-67571244Part 1: Dose Escalation

Purpose

The main purpose of this study are to determine the recommended Phase 2 dose(s) (RP2D) route of administration, schedule and the maximum tolerated dose (MTD) in Part 1 and to determine the safety and tolerability of JNJ-67571244 at the RP2D regimen(s) and to evaluate the preliminary clinical activity of JNJ-67571244 in Part 2.

Detailed Description

      This is first-in-human (FIH) Phase 1, open-label, multicenter, dose escalation study with
      dose expansion to evaluate the safety, tolerability, and preliminary antitumor activity of
      JNJ-67571244 in adult participants with relapsed or refractory acute myeloid leukemia (AML)
      or high-risk or very high-risk myelodysplastic syndromes (MDS) who are ineligible for or have
      exhausted standard therapeutic options. The study is divided into 3 periods: a Screening
      Phase (within 28 days before the first dose of study drug), a Treatment Phase (first dose of
      study drug until the last dose of study drug) and a Post-treatment Follow-up Phase (up to the
      end of study participation or end of study). Duration of study is 2.3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1: Dose EscalationExperimentalParticipants will receive JNJ-67571244. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified.
  • JNJ-67571244
Part 2: Dose ExpansionExperimentalParticipants in 2 expansion cohorts of acute myeloid leukemia (AML) or either high-risk myelodysplastic syndromes (MDS) or very high-risk MDS will receive JNJ-67571244 at the RP2D determined in Part 1.
  • JNJ-67571244

Eligibility Criteria

        Inclusion Criteria:

          -  A diagnosis of:

             a) Acute Myeloid Leukemia (AML) according to the World Health Organization 2008
             criteria with relapsed or refractory disease and ineligible for or have exhausted
             standard therapeutic options b) high-risk or very high-risk Myelodysplastic Syndrome
             (MDS) according to International Prognostic Scoring System (IPSS-R) and relapsed or
             refractory after at least 1 course of hypomethylating therapy and ineligible for or
             have exhausted standard therapeutic options per investigator discretion should be
             included

          -  Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1

          -  Women of childbearing potential must have a negative pregnancy test at screening and
             prior to the first dose of study drug using a highly sensitive pregnancy test (either
             serum or urine beta human chorionic gonadotropin [beta-hCG])

          -  Chemistry laboratory parameters within the following range during screening:

             a) aspartate transaminase (AST) and alanine aminotransferase (ALT) less than or equal
             to (<=) 3* upper limit of normal (ULN), b) Total bilirubin <=1.5*ULN; participants
             with congenital bilirubinemia, such as Gilbert's syndrome, may enroll if conjugated
             bilirubin is within normal range, c) Creatinine clearance calculated or measured
             creatinine clearance greater than or equal to (>=) 30 milliliters per minute (mL/min)

          -  Before the first dose of study drug:

               1. Women of childbearing potential and fertile men who are sexually active must
                  agree to use a highly effective method of contraception (less than [<] 1 percent
                  {%} year failure rate from the time of signing the informed consent form [ICF])
                  during the study and for 90 days after the last dose of study drug. Contraception
                  must be consistent with local regulations regarding the use of birth control
                  methods for participants participating in clinical trials. 1) Participant must
                  agree to practice a highly effective method of contraception (failure rate of <1%
                  per year when used consistently and correctly). Examples of highly effective
                  contraceptives include: a) user-independent methods: implantable progestogen-only
                  hormone contraception associated with inhibition of ovulation; intrauterine
                  device; intrauterine hormone-releasing system; vasectomized partner; b)
                  user-dependent methods: combined (estrogen- and progestogen-containing) hormonal
                  contraception associated with inhibition of ovulation: oral, intravaginal, and
                  transdermal; progestogen-only hormone contraception associated with inhibition of
                  ovulation: oral and injectable, c) In addition to the highly effective method of
                  contraception, a man: 1) Who is sexually active with a woman of childbearing
                  potential must agree to use a barrier method of contraception (for example,
                  condom with spermicidal foam/gel/film/cream/suppository), 2) Who is sexually
                  active with a woman who is pregnant must use a condom, c) Women and men must
                  agree not to donate eggs (ova, oocytes) or sperm, respectively, during the study
                  and for 90 days after the last dose of study drug

        Exclusion Criteria:

          -  Willing and able to undergo allogenic stem cell transplant <=6 months before the first
             dose of study drug, has evidence of graft versus host disease, or requires
             immunosuppressant therapy (exception: daily doses less than 10 milligram (mg)
             prednisone or equivalent are allowed for adrenal replacement)

          -  For Part 1 only, prior treatment with CD33 targeting therapy targeting T-cell
             redirection (for example, CD-3 redirection technology or chimeric antigen receptor
             [CAR]-T-cell therapy)

          -  For Part 1 only, prior Grade 3 cytokine release syndrome (CRS) related to any T-cell
             redirection (for example, CD-3 redirection technology or CAR-T cell therapy)

          -  Prior treatment with a checkpoint inhibitor such that the first dose of JNJ-67571244
             would occur within less than 5 half-lives. Prior treatment with chemotherapy, targeted
             therapy, immunotherapy, radiotherapy, or treatment with an investigational anticancer
             agent, an investigational drug (including investigational vaccines), within 2 weeks
             prior to the first dose or at least 4 half-lives, whichever is less, or currently
             receiving investigational therapy in a clinical trial. Hydroxyurea may be used

          -  Toxicities (except for alopecia, peripheral neuropathy, thrombocytopenia) from
             previous anticancer therapies that have not resolved to baseline levels or to Grade 1
             or less
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
Time Frame:Up to 100 days after the last dose of study drug or until the start of a subsequent anticancer therapy, whichever comes first (that is up to 2.3 years)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Part 1 and Part 2: Serum Concentrations of JNJ-67571244
Time Frame:Approximately 2.3 years
Safety Issue:
Description:Serum samples will be analyzed to determine concentrations of JNJ-67571244 using a validated immunoassay method.
Measure:Part 1 and 2: Systemic Cytokine Concentrations
Time Frame:Approximately 2.3 years
Safety Issue:
Description:Serum cytokine (Interleukin [IL]-2, IL-6, IL-8, IL-10, and Interferon [IFN]-alpha, IFN-delta with same unit of measurement) concentrations will be measured for biomarker assessment.
Measure:Number of Participants with Depletion of CD33-Expressing Cells
Time Frame:Approximately 2.3 years
Safety Issue:
Description:Number of participants with depletion of CD33-expressing cells will be assessed.
Measure:Part 1 and 2: Concentration of Markers of T-Cell Activation
Time Frame:Up to 24 days
Safety Issue:
Description:Levels of T-cell activation marker CD25 will be reported as measured by flow cytometry and cytometry by time of flight (CyTOF). T-cell activation will also be assessed by measuring cytokine release.
Measure:Part 1 and 2: Number of Participants with JNJ-67571244 Antibodies
Time Frame:Week 1 (Day 1) up to post treatment Week 8
Safety Issue:
Description:Anti-JNJ-67571244 antibodies will be evaluated in serum samples collected from all participants and the titer of confirmed positive samples will be reported.
Measure:Part 1 and Part 2: Duration of response (DOR)
Time Frame:Approximately 2.3 years
Safety Issue:
Description:DOR is calculated from date of initial documentation of a response (complete response (CR) and incomplete blood count recovery (CRi) (AML) or CR and partial response (PR) [MDS]) to the date of first documented evidence of relapse, defined in disease-specific response criteria, or death, whichever occurs first.
Measure:Part 1 and Part 2: Time to response (TTR)
Time Frame:Approximately 2.3 years
Safety Issue:
Description:TTR defined for the responders as the time from the date of first dose of study drug to the date of initial documentation of a response (CR and CRi [AML] or CR and PR [MDS]), as defined in the disease-specific response criteria.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

April 23, 2021