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CD20-positive B-cell Non-Hodgkin LymphomaPhase 1NCT01569750

A Study Combining Ibrutinib With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With CD20-Positive B-Cell Non Hodgkin Lymphoma

A Phase 1 study testing Part 1, Cohort 1, Part 1, Cohort 2 and Part 1, Cohort 3 in people with CD20-positive B-cell Non-Hodgkin Lymphoma, run by Janssen Research & Development, LLC at 7 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to identify if, and at what dose, ibrutinib may be administered with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and to document responses of this combination in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Part 1, Cohort 1, Part 1, Cohort 2 and Part 1, Cohort 3
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
7 sitesin 2 countries
Study dates
14 Jun 2012to 4 Sep 2014
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

  • Histopathologically-confirmed CD20-positive B-cell non Hodgkin lymphoma disease for whom R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) is an appropriate therapy (diffuse large B-cell lymphoma, mantle cell lymphoma, or follicular lymphoma); for the expansion cohort, at least 1 cohort will only include patients with newly diagnosed diffuse large B-cell lymphoma
  • Stage I AX (bulk defined as single lymph node mass >=10 cm in diameter) to Stage IV disease
  • At least 1 measurable site of disease based on the Revised Response Criteria for Malignant Lymphoma
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Adequate bone marrow, liver, and renal function

Who cannot join

  • History of protocol-defined disallowed therapies
  • Prior multidrug chemotherapy treatment for lymphoma
  • History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug
  • Major surgery within 3 weeks before enrollment
  • Known bleeding diatheses, platelet dysfunction disorders, or requires therapeutic anticoagulation
  • Known lymphoma of the central nervous system
Show all 11Show fewer
  • Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association Class III or IV heart failure, uncontrolled angina, pericardial disease, cardiac amyloidosis, clinically significant cardiac arrhythmia, or left ventricular ejection fraction outside of institutional limits
  • Active systemic infection requiring treatment including hepatitis B and hepatitis C infection
  • Documented or suspected human immunodeficiency virus infection
  • Diagnosed or treated for a malignancy other than non-Hodgkin lymphoma except; adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ of the breast, or other solid tumors curatively treated with no evidence of disease for >5 years
  • Has any condition that, in the opinion of the investigator, would make study participation not be in the best interest (eg, compromise the well-being) of the patient or that could prevent, limit, or confound the protocol-specified assessments

Trial locations and contacts

7 sites in 2 countries.

7 sites in 2 countries

United States4 sites

  • Study site

    Houston, Texas

  • Study site

    Nashville, Tennessee

  • Study site

    New York, New York

  • Study site

    Rochester, New York

Other trials in United States

France3 sites

  • Study site

    Lille

  • Study site

    Paris

  • Study site

    Vandœuvre-lès-Nancy

Other trials in France

About this study

Official title: A Phase 1b Study Combining Ibrutinib With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Subjects With CD20-Positive B-Cell Non Hodgkin Lymphoma (NHL)

The purpose of this study is to identify if, and at what dose, ibrutinib may be administered with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and to document responses of this combination in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).

Read the detailed description

This is an open-label (individuals will know the identity of study treatments), dose escalation study to establish the recommended dose of ibrutinib combined with standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in approximately 33 adults with CD20-positive B-cell non-Hodgkin lymphoma (NHL) for whom R-CHOP is an appropriate therapy. There will be 3 periods of the study: a pretreatment (screening) period of up to 28 days before enrollment; an open-label treatment period (up to 6 cycles of ibrutinib and R-CHOP; ending at the end-of-treatment visit); and a posttreatment follow-up period until the end of study (maximum of up to 1 year after the last patient has completed the end-of-treatment visit). There are 2 parts to the study (dose escalation [Part 1] and expansion [Part 2]). During the dose escalation period, the "3+3" design will be applied and approximately 18 patients with CD20 positive B cell NHL (diffuse large B-cell lymphoma [DLBCL], mantle cell lymphoma [MCL], and follicular lymphoma [FL]) may be enrolled. Patients will be assigned to cohorts of increasing oral daily doses of ibrutinib (280, 420, and 560 mg) administered in combination with R-CHOP. The maximum tolerated dose (MTD), assessed in Cycle 1 (dose-limiting toxicity [DLT] period), is defined as the highest dose of the combination regimen at which <=33% of patients experience DLT. Baseline and follow-up electrocardiograms will be performed throughout the study. A Study Evaluation Team will review all available data upon completion of the first cycle for all patients at each dose cohort to determine DLTs, if dose escalation is acceptable, and subsequently will determine the recommended Phase 2 dose. Once the recommended Phase 2 dose is determined, approximately 15 patients with newly diagnosed DLBCL will be entered into the expansion cohort at the dose level selected to further assess the safety, pharmacokinetics, pharmacodynamics, pharmacogenomics, and activity of the combination. Patients whose disease has not progressed at the end of Cycle 1 will continue to receive ibrutinib and R CHOP up to a maximum of 6 cycles. During the posttreatment follow-up period, long term safety, survival status, disease progression, and subsequent antilymphoma therapy will be collected. The study will end 1 year after the last patient has completed the end of treatment visit.

Being tested
Part 1, Cohort 1, Part 1, Cohort 2, Part 1, Cohort 3, Part 2, Cohort 1, Part 2, Cohort 2
Keywords
CD20-positive B-cell non-Hodgkin lymphoma, Diffuse large B-cell lymphoma, Mantle cell lymphoma, Follicular lymphoma, Ibrutinib, R-CHOP, Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Lymphoma, Follicular

What participants receive

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

  • Part 1, Cohort 1Drug

    Type=exact number, unit=mg, number=280, form=capsule, route=oral use. Escalating doses of ibrutinib (starting on Day 3 for Cycle 1 and on Day 1 for subsequent cycles) administered once daily in with standard-of-care doses of R-CHOP until maximum tolerated dose is achieved.

  • Part 1, Cohort 2Drug

    Type=exact number, unit=mg, number=420, form=capsule, route=oral use. Escalating doses of ibrutinib (starting on Day 3 for Cycle 1 and on Day 1 for subsequent cycles) administered once daily in with standard-of-care doses of R-CHOP until maximum tolerated dose is achieved.

  • Part 1, Cohort 3Drug

    Type=exact number, unit=mg, number=560, form=capsule, route=oral use. Escalating doses of ibrutinib (starting on Day 3 for Cycle 1 and on Day 1 for subsequent cycles) administered once daily in with standard-of-care doses of R-CHOP until maximum tolerated dose is achieved.

  • Part 2, Cohort 1Drug

    Ibrutinib at the recommended Part 1 dose administered once daily with standard-of-care doses of R-CHOP in patients with newly diagnosed diffuse large B-cell lymphoma.

  • Part 2, Cohort 2Drug

    Ibrutinib at the recommended Part 1 dose administered once daily with standard-of-care doses of R-CHOP in patients with newly diagnosed with B-cell non-Hodgkin lymphoma.

Study groups in NCT01569750
Study groupRoleWhat they receive
IbrutinibExperimentalPart 1 (Dose Escalation): Escalating doses of ibrutinib (starting on Day 3 for Cycle 1 and on Day 1 for subsequent cycles) administered once daily in with standard-of-care doses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) until maximum tolerated dose is achieved. Part 2: Ibrutinib at the recommended Part 1 dose administered once daily with standard-of-care doses of R-CHOP.
Receives: Drug: Part 1, Cohort 1; Drug: Part 1, Cohort 2; Drug: Part 1, Cohort 3; Drug: Part 2, Cohort 1; Drug: Part 2, Cohort 2

What is being measured

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

  1. Part 1 maximum tolerated dose of ibrutinib

    The Part 1 maximum tolerated dose (MTD) is the Part 2 recommended ibrutinib dose.

    Measured: Up to Cycle 1, Day 21 in Part 1

Secondary outcomes (15)

  1. The number of participants affected by a dose-limiting toxicity

    Measured: Up to Cycle 6, Day 21 in Part 1

  2. Number of participants with potential drug-drug interactions between ibrutinib and vincristine

    Measured: Up to Cycle 6, Day 21 in Part 2

  3. Overall response rate

    Measured: Up to Cycle 6, Day 21 in Part 2

  4. Duration of response

    Measured: Up to Cycle 6, Day 21 in Part 2

  5. Progression-free survival

    Measured: Up to Cycle 6, Day 21 in Part 2

  6. Mean plasma concentrations of ibrutinib

    Measured: Up to Cycle 6, Day 21 in Part 2

  7. Maximum observed plasma concentration of ibrutinib

    Measured: Up to Cycle 6, Day 21 in Part 2

  8. Time to reach the maximum plasma concentration of ibrutinib

    Measured: Up to Cycle 6, Day 21 in Part 2

  9. Area under the plasma concentration-time curve from time 0 to 24 hours of ibrutinib

    Measured: Up to Cycle 6, Day 21 in Part 2

  10. Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve of ibrutinib

    Measured: Up to Cycle 6, Day 21 in Part 2

  11. Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve of vincristine

    Measured: Up to Cycle 6, Day 21 in Part 2

  12. Partial area under the plasma concentration versus time curve of vincristine

    Measured: Up to Cycle 6, Day 21 in Part 2

  13. The number of participants with pharmacodynamic markers of ibrutinib in peripheral blood mononuclear cells

    Measured: Up to Cycle 6, Day 21 in Part 2

  14. The number of participants with biomarkers predictive of clinical response

    Measured: Up to Cycle 6, Day 21 in Part 2

  15. The number of participants affected by an adverse event

    Measured: Up to 30 days after the last dose of study medication

Timeline

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

  1. First posted3 Apr 2012 (estimated)
  2. Study start14 Jun 2012
  3. Primary completion4 Sep 2014
  4. Study completion4 Sep 2014

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01569750
Sponsor's protocol ID
CR100844
Other IDs
PCI-32765DBL1002, 2012-000546-35
Status last verified
Aug 2017
First submitted
30 Mar 2012
Last updated
22 Aug 2017
Results posted
No
Data monitoring committee
Yes
FDA-regulated device
No

Publications

  • Younes A, Thieblemont C, Morschhauser F, Flinn I, Friedberg JW, Amorim S, Hivert B, Westin J, Vermeulen J, Bandyopadhyay N, de Vries R, Balasubramanian S, Hellemans P, Smit JW, Fourneau N, Oki Y. Combination of ibrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for treatment-naive patients with CD20-positive B-cell non-Hodgkin lymphoma: a non-randomised, phase 1b study. Lancet Oncol. 2014 Aug;15(9):1019-26. doi: 10.1016/S1470-2045(14)70311-0. Epub 2014 Jul 17.

    PubMed 25042202

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Part 1, Cohort 1, Part 1, Cohort 2 and Part 1, Cohort 3 in people with CD20-positive B-cell Non-Hodgkin Lymphoma, run by Janssen Research & Development, LLC at 7 sites in 2 countries.

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 11 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: finished, as of the sponsor's last update on 22 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, France. Whether a site is taking part right now should be confirmed with that site. See every site.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 maximum tolerated dose of ibrutinib (time frame: Up to Cycle 1, Day 21 in Part 1). 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 NCT01569750, which also lists 1 linked publication.

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 22 Aug 2017.

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