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

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ClinicalTrials.gov Identifier: NCT03915379
Recruitment Status : Recruiting
First Posted : April 15, 2019
Last Update Posted : August 15, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Myelodysplastic Syndromes Drug: JNJ-67571244 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 28, 2019
Estimated Primary Completion Date : June 4, 2021
Estimated Study Completion Date : July 22, 2021


Arm Intervention/treatment
Experimental: Part 1: Dose Escalation
Participants 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.
Drug: JNJ-67571244
JNJ-67571244 will be administered intravenously.

Experimental: Part 2: Dose Expansion
Participants 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.
Drug: JNJ-67571244
JNJ-67571244 will be administered intravenously.




Primary Outcome Measures :
  1. 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 ]
    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.

  2. Part 1: Number of Participants with Dose-Limiting Toxicity (DLTs) [ Time Frame: Up to 28 days ]
    Number of participants with dose-limiting toxicity will be assessed. The DLTs are based on drug-related adverse events and defined as any of the following events: infusion-related reactions, non-hematologic toxicity of Grade 3 or higher, or hematologic toxicity.

  3. Part 1: Severity of DLT as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) [ Time Frame: Up to 28 days ]
    The DLT evaluation period is defined as the first 28 days after a participant's first infusion (Day 1). Severity criteria is based on Grade 1, 2, 3, 4 and 5, will be assessed by the investigator as per below grades. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening consequences; Grade 5: Death related to adverse event.

  4. Part 2: Overall Response Rate (ORR) [ Time Frame: Approximately 2.3 years ]
    ORR is defined as the percentage of participants who have complete response (CR) and incomplete blood count recovery (CRi) or CR and partial response (PR) as per modified International Working Group response (IWGR) criteria.


Secondary Outcome Measures :
  1. Part 1 and Part 2: Serum Concentrations of JNJ-67571244 [ Time Frame: Approximately 2.3 years ]
    Serum samples will be analyzed to determine concentrations of JNJ-67571244 using a validated immunoassay method.

  2. Part 1 and 2: Systemic Cytokine Concentrations [ Time Frame: Approximately 2.3 years ]
    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.

  3. Number of Participants with Depletion of CD33-Expressing Cells [ Time Frame: Approximately 2.3 years ]
    Number of participants with depletion of CD33-expressing cells will be assessed.

  4. Part 1 and 2: Concentration of Markers of T-Cell Activation [ Time Frame: Up to 24 days ]
    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.

  5. Part 1 and 2: Number of Participants with JNJ-67571244 Antibodies [ Time Frame: Week 1 (Day 1) up to post treatment Week 8 ]
    Anti-JNJ-67571244 antibodies will be evaluated in serum samples collected from all participants and the titer of confirmed positive samples will be reported.

  6. Part 1 and Part 2: Duration of response (DOR) [ Time Frame: Approximately 2.3 years ]
    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.

  7. Part 1 and Part 2: Time to response (TTR) [ Time Frame: Approximately 2.3 years ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03915379


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
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United States, Kansas
University of Kansas Cancer Center Not yet recruiting
Fairway, Kansas, United States, 66205
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
University of Massachusetts Not yet recruiting
Worcester, Massachusetts, United States, 01655
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
United States, North Carolina
Levine Cancer Institute, Carolinas HealthCare System Not yet recruiting
Charlotte, North Carolina, United States, 28204
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Spain
Hosp. Clinic I Provincial de Barcelona Recruiting
Barcelona, Spain, 08036
Hosp. Univ. Fund. Jimenez Diaz Recruiting
Madrid, Spain, 28040
Hosp. Virgen Del Rocio Recruiting
Sevilla, Spain, 41013
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Additional Information:
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03915379     History of Changes
Other Study ID Numbers: CR108582
2018-004452-37 ( EudraCT Number )
67571244AML1001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: April 15, 2019    Key Record Dates
Last Update Posted: August 15, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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

URL: https://www.janssen.com/clinical-trials/transparency

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Neoplasms by Histologic Type
Neoplasms
Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions