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), 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), 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 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 by intravenous (IV) infusion. 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) and high-risk myelodysplastic syndromes (MDS) will receive JNJ-67571244 IV at the recommended Phase 2 dose (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 or induction therapy

          -  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) 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:

          -  Prior treatment with 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)

          -  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:Approximately 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 (CR and CRi [AML] or CR and PR [MDS]) to the date of first documented evidence of relapse, defined in disease-specific response criteria, or death.
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

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