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Leukemia, Lymphocytic, Chronic, B-CellPhase 1NCT02743546

Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Duvortuxizumab (JNJ-64052781) Plus Ibrutinib in Lymphoma

A Phase 1 study testing Duvortuxizumab and Ibrutinib in people with Leukemia, Lymphocytic, Chronic, B-Cell and Lymphoma, Large B-Cell, Diffuse, run by Janssen Research & Development, LLC.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this study is to determine whether duvortuxizumab and ibrutinib can be combined safely and to establish the maximum tolerated dose (MTD) in Part 1 and the recommended Phase 2 dose (RP2D) and to further explore the safety of duvortuxizumab in combination with ibrutinib at the RP2D in participants with… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Duvortuxizumab and Ibrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
20 Jul 2016to 31 Mar 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The participant has a B-cell malignancy (diffuse large B-cell lymphoma [DLBCL], follicular lymphoma [FL], mantle cell lymphoma [MCL], or chronic lymphocytic leukemia [CLL]) with tumor progression following at least one (MCL and CLL) or two (DLBCL and FL) prior standard therapies
  • The participant has a radiographically measurable tumor that requires treatment according to the treating physician
  • The participant is able to carry out daily life activities with significant difficulty
  • The participant has adequate organ and blood cell counts
  • Sexually active participants must use medically acceptable methods of contraception during the course of the study

Who cannot join

  • The participant has a brain tumor or significant side effects, including severe neurological side effects, from a previous anti-cancer treatment
  • Current severe, uncontrolled systemic disease including an ongoing, active infection or history of clinically significant heart problems
  • History of autoimmune disease, allogeneic hematopoietic stem cell transplant, or organ transplant
  • The participant has received any of the following: ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitor at any time; an agent targeting CD19-positive cells or CD3-expressing T cells at any time; or warfarin, a vitamin K antagonist, or a blood transfusion (red blood cells and/or platelets) within 1 week of starting the study
  • The participant is pregnant, breastfeeding, or planning to become pregnant or father a child

About this study

Official title: A Phase 1b Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of the Combination of Duvortuxizumab With Ibrutinib in Subjects With B-Cell Malignancies

The purpose of this study is to determine whether duvortuxizumab and ibrutinib can be combined safely and to establish the maximum tolerated dose (MTD) in Part 1 and the recommended Phase 2 dose (RP2D) and to further explore the safety of duvortuxizumab in combination with ibrutinib at the RP2D in participants with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL) in Part 2.

Read the detailed description

This is an open-label (identity of study drug will be known to participant and study staff), multicenter (when more than one hospital or medical school team work on a medical research study), Phase 1b study. The purpose of this study is to see if duvortuxizumab in combination with ibrutinib is safe and useful for treating participants with B-cell malignancies. This study will be conducted in 2 parts: Part 1: Dose Optimization and Part 2: Dose Expansion. Part 1 will determine what dose of duvortuxizumab can be given safely with the standard dose of ibrutinib to participants with previously treated B-cell malignancies. Part 2 will look at how previously treated DLBCL, FL, MCL, and CLL participants respond to a safe dose of duvortuxizumab in combination with ibrutinib. Part 2 will also test whether the dose from Part 1 is an effective cancer therapy. The study consists of a Screening Phase, an ibrutinib Run-In Phase (Part 2 only), a combination (duvortuxizumab plus ibrutinib) Treatment Phase (Day 1, Cycle 1 and continues until the completion of the End-of-Treatment Visit), End-of-Treatment Visit (30 days (+7 days) after the last dose of study drug), and Post-treatment Follow-up Phase. The end of the study will be defined as 12 months after the last participant has received the first dose of study treatment. Participants' safety will be monitored throughout the study.

Being tested
Duvortuxizumab, Ibrutinib
Keywords
B-Cell, Malignancy, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Lymphoma, Follicular, Lymphocytic, Chronic, B-Cell, JNJ-64052781, Ibrutinib
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Neoplasms, Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DuvortuxizumabDrug

    Duvortuxizumab will be administered at starting dose of 15 nanogram per kilogram (ng/kg) as an intravenous (IV) infusion during Part 1 (Dose Optimization) and at RP2D level determined in Part 1 during Part 2 (Dose Expansion). Participants will receive duvortuxizumab either with or without a priming dose. Participants who receive a priming dose will have infusions on Days 1, 8, and 22 of an initial 35-day cycle and then on Days 1 and 15 of 28-day cycles thereafter. Participants who do not receive a priming dose will have infusions on Days 1 and 15 of 28-day cycles.

  • IbrutinibDrug

    Ibrutinib will be administered at 560 milligram per day (mg/day) orally once daily during Part 1 (Dose Optimization) and at a dose of 420 mg/day (for participants with CLL) or 560 mg/day (for participants with DLBCL, FL, or MCL) during Part 2 (Dose Expansion). In Part 1, ibrutinib will be initiated on Day 1 of the initial treatment cycle. In Part 2, ibrutinib will be initiated on Day -7 prior to the initial treatment cycle.

Study groups in NCT02743546
Study groupRoleWhat they receive
Dose Optimization:Participant with Certain B-Cell MalignanciesExperimentalParticipants with certain B-cell malignancies (diffuse large B-cell lymphoma [DLBCL], mantle cell lymphoma [MCL], or follicular lymphoma [FL]) will receive rising doses of intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met. Dose escalation will continue until the recommended phase 2 dose or maximum tolerated dose is reached.
Receives: Drug: Duvortuxizumab; Drug: Ibrutinib
Dose Expansion: Participants with DLBCLExperimentalParticipants with DLBCL will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.
Receives: Drug: Duvortuxizumab; Drug: Ibrutinib
Dose Expansion: Participants with FLExperimentalParticipants with FL will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.
Receives: Drug: Duvortuxizumab; Drug: Ibrutinib
Dose Expansion: Participants with MCLExperimentalParticipants with MCL will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.
Receives: Drug: Duvortuxizumab; Drug: Ibrutinib
Dose Expansion: Participants with CLLExperimentalParticipants with chronic lymphocytic leukemia (CLL) will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.
Receives: Drug: Duvortuxizumab; Drug: Ibrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Number of Participants With Dose Limiting Toxicity

    Dose limiting toxicity is based on adverse events and includes unacceptable hematologic toxicity, unacceptable non-hematologic toxicity, and laboratory abnormalities of Grade 4 or higher.

    Measured: Approximately 9 months

  2. Part 1 and Part 2: Number of Participants With Adverse Events

    An adverse event (AE) is any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship.

    Measured: Approximately 2 years

  3. Part 1 and Part 2: Number of Participants With Serious Adverse Events

    A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital abnormality.

    Measured: Approximately 2 years

  4. Part 1 and Part 2: Change in Clinical Laboratory Values From Baseline

    Standard clinical chemistry and hematology panels will be used to evaluate changes in laboratory parameters in blood samples collected pre- and post-treatment.

    Measured: Baseline and 2 years

Secondary outcomes (16)

  1. Part 1 and Part 2: Area Under the Serum Concentration-Time Curve From Time [0 to t] (AUC[0-t]) of Duvortuxizumab

    The AUC[0-t] is the area under the duvortuxizumab serum concentration-time curve from time [0 to t].

    Measured: Approximately 2 years

  2. Part 1 and Part 2: Area Under the Serum Concentration-Time Curve From Time [0 to t] (AUC[0-t]) of Ibrutinib

    The AUC[0-t] is the area under the ibrutinib serum concentration-time curve from time [0 to t].

    Measured: Approximately 2 years

  3. Part 1 and 2: Maximum Serum Concentration (Cmax) of Duvortuxizumab

    The Cmax is the maximum observed serum concentration of duvortuxizumab.

    Measured: Approximately 2 years

  4. Part 1 and 2: Maximum Serum Concentration (Cmax) of Ibrutinib

    The Cmax is the maximum observed serum concentration of ibrutinib.

    Measured: Approximately 2 years

  5. Part 1 and 2: Half-Life (t1/2) of Duvortuxizumab

    The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration.

    Measured: Approximately 2 years

  6. Part 1 and 2: Half-Life (t1/2) of Ibrutinib

    The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration.

    Measured: Approximately 2 years

  7. Part 1 and 2: Total Systemic Clearance (CL) of Duvortuxizumab

    The CL is a quantitative measure of the rate at which duvortuxizumab is removed from the body.

    Measured: Approximately 2 years

  8. Part 1 and 2: Total Systemic Clearance (CL) of Ibrutinib

    The CL is a quantitative measure of the rate at which ibrutinib is removed from the body.

    Measured: Approximately 2 years

  9. Part 1 and 2: Volume of Distribution at Steady-State (Vss) of Duvortuxizumab

    The Vss is defined as the theoretical volume in which the total amount of duvortuxizumab would be uniformly distributed to produce the desired serum concentration of duvortuxizumab at steady state.

    Measured: Approximately 2 years

  10. Part 1 and 2: Volume of Distribution at Steady-State (Vss) of Ibrutinib

    The Vss is defined as the theoretical volume in which the total amount of ibrutinib would be uniformly distributed to produce the desired serum concentration of Ibrutinib at steady state.

    Measured: Approximately 2 years

  11. Part 1 and Part 2: Number of Participants with Anti-Duvortuxizumab Antibodies

    Plasma levels of antibodies to duvortuxizumab will be assessed for evaluation of potential immunogenicity.

    Measured: Approximately 2 years

  12. Part 1 and Part 2: Objective Tumor Response

    Objective tumor response is represented by participants who achieve a complete response (CR) or partial response (PR) to study treatment per the criteria for response assessment of Non-Hodgkin's Lymphoma (participants with diffuse large B-cell lymphoma [DLBCL], follicular lymphoma [FL], and mantle cell lymphoma [MCL]) or the International Workshop on chronic lymphocytic leukemia Criteria (IWCLL) (participants with CLL)

    Measured: Approximately 2 years

  13. Part 1 and Part 2: Number of Participants With Complete Response (CR)

    The CR rate is frequency of participants who achieve a complete response to study treatment according to the Criteria for Response Assessment of Non-Hodgkin's Lymphoma (participants with DLBCL, FL, and MCL) or the IWCLL Criteria (for participants with CLL).

    Measured: Approximately 2 years

  14. Part 1 and Part 2: Duration of Response

    The Duration of Response is defined as the time from the first observed response (CR or partial response [PR]) to documented disease progression or death due to any cause.

    Measured: Approximately 2 years

  15. Part 1 and Part 2: 1-year Progression Free Survival (PFS)

    Progression free survival is defined as the time from first enrollment into the study to documented disease progression or death due to any cause.

    Measured: 1 year

  16. Part 1 and Part 2: 1-year Overall Survival

    One-year survival is defined as the percentage of participants surviving 1 year after entering into the study.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Apr 2016 (estimated)
  2. Study start20 Jul 2016 (estimated)
  3. Primary completion30 Sep 2018 (estimated)
  4. Study completion31 Mar 2020 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02743546
Sponsor's protocol ID
CR108158
Other IDs
64052781NHL1001, 2016-000721-39, 2016
Status last verified
Jan 2025
First submitted
15 Apr 2016
Last updated
3 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Duvortuxizumab and Ibrutinib in people with Leukemia, Lymphocytic, Chronic, B-Cell and Lymphoma, Large B-Cell, Diffuse, run by Janssen Research & Development, LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Number of Participants With Dose Limiting Toxicity (time frame: Approximately 9 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02743546.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2025.

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