Clinical trial NCT03915379: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-04-16
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: 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)
measure: Part 1: Number of Participants with Dose-Limiting Toxicity (DLTs)
timeFrame: Up to 28 days
measure: Part 1: Severity of DLT as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
timeFrame: Up to 28 days
measure: Part 2: Overall Response Rate (ORR)
timeFrame: Approximately 2.3 years
Secondary outcomes:
measure: Part 1 and Part 2: Serum Concentrations of JNJ-67571244
timeFrame: Approximately 2.3 years
measure: Part 1 and 2: Systemic Cytokine Concentrations
timeFrame: Approximately 2.3 years
measure: Number of Participants with Depletion of CD33-Expressing Cells
timeFrame: Approximately 2.3 years
measure: Part 1 and 2: Concentration of Markers of T-Cell Activation
timeFrame: Up to 24 days
measure: Part 1 and 2: Number of Participants with JNJ-67571244 Antibodies
timeFrame: Week 1 (Day 1) up to post treatment Week 8
measure: Part 1 and Part 2: Duration of response (DOR)
timeFrame: Approximately 2.3 years
measure: Part 1 and Part 2: Time to response (TTR)
timeFrame: Approximately 2.3 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: NYU Hematology Associates
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute, Carolinas HealthCare System
state: North Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: München
country: Germany
facility: Klinikum der Universitaet Muenchen
city: Münster
country: Germany
facility: Universitätsklinikum Münster; Med. Klinik A - Germany
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: