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CD20 PositivePhase 1NCT02219737

Ibrutinib and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

A Phase 1 study testing Carboplatin, Etoposide and Ibrutinib in people with CD20 Positive and Recurrent Diffuse Large B-Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.

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

This phase I trial studies the side effects and best dose of ibrutinib when given together with rituximab, ifosfamide, carboplatin, and etoposide (combination chemotherapy) in treating patients with diffuse large B-cell lymphoma (DLBCL) that has returned after a period of improvement (relapsed) or has not responded to… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Carboplatin, Etoposide and Ibrutinib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
12 Sep 2014to 11 May 2017
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

  • Autologous transplant eligible patients must have histologically or cytologically confirmed cluster of differentiation (CD)20 positive relapsed or refractory DLBCL by biopsy within 45 days prior to subject enrollment and must have been previously treated with an anthracycline and rituximab-containing regimen
  • Baseline fludeoxyglucose F 18 (FDG)-positron emission tomography (PET) scans must demonstrate positive lesions compatible with computed tomography (CT) defined anatomical tumor sites
  • CT scan showing at least:
  • 2 or more clearly demarcated lesions/nodes with a long axis > 1.5 cm and short axis >= 1.0 cm OR
  • 1 clearly demarcated lesion/node with a long axis > 2.0 cm and short axis >= 1.0 cm
  • Patient must have been previously treated for B cell non-Hodgkin lymphoma with any of the allowable below:
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  • First-line treatment with rituximab and an anthracycline-based chemotherapy
  • Monotherapy rituximab, dosed prior to first-line rituximab combined with anthracycline containing chemotherapy, or as maintenance therapy
  • Radiotherapy as part of the first-line treatment plan including anthracycline and rituximab
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 6 weeks
  • Absolute neutrophil count >= 1,000/mcL (unless due to lymphoma involvement of the bone marrow)
  • Platelets >= 75,000/mcL (unless due to lymphoma involvement of the bone marrow)
  • Total bilirubin < 1.5 x within normal institutional limits (unless due to lymphoma involvement of liver or a known history of Gilbert's disease)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 × institutional upper limit of normal (unless due to lymphoma involvement of liver)
  • Creatinine within normal institutional limits OR creatinine clearance >= 40 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (unless due to lymphoma)
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 90 days after the last dose of study drug; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Ibrutinib must be discontinued 7 days before (when possible) until 7 days after major surgery, and 3 days before (when possible) until 3 days after minor surgery; thus, patients to be enrolled on an ibrutinib trial must have completed major surgery within 4 weeks before initiating treatment, and/or must have completed minor surgery > 3 days before initiating treatment
  • Ability to understand and the willingness to sign a written informed consent document
  • Must be able to swallow whole capsules

Who cannot join

  • Patients who have had chemotherapy or radiotherapy =< 21 days (=< 6 weeks for monoclonal antibodies) prior to first administration of study treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who are receiving any other investigational agents
  • Patients with known brain metastases should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib or R-ICE
  • Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor; strong inhibitors or inducers of CYP3A4/5 should be avoided and moderate inhibitors or inducers should be used with caution; it is important to regularly consult a frequently-updated list; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; recent infections requiring systemic treatment need to have completed therapy > 14 days before the first dose of study drug
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  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ibrutinib R-ICE
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are eligible, unless the patient's CD4 count is below the institutional lower limit of normal, or the patient is taking prohibited CYP3A4/5 strong inhibitors or inducers
  • Patients may not have received any anti-cancer therapy for their primary relapsed (rel)/refractory (ref) DLBCL with the exception of palliative radiation therapy (RT)
  • Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in (or as evidenced by) declining platelet or hemoglobin (Hgb) levels within the 4 weeks prior to first dose of study drug
  • Presence of transfusion-dependent thrombocytopenia
  • Prior exposure to bruton tyrosine kinase (BTK) inhibitor
  • History of prior malignancy, with the exception of the following:
  • Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician
  • Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
  • Adequately treated cervical carcinoma in situ without current evidence of disease
  • Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification, or history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to first dose with study drug
  • Unable to swallow capsules, or disease significantly affecting gastrointestinal function or resection of the stomach or small bowel, or symptomatic-inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
  • Serologic status reflecting active hepatitis B or C infection; patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody will need a negative polymerase chain reaction (PCR) prior to enrollment (PCR positive patients will be excluded); hepatitis C antibody positive patients are eligible if PCR is negative
  • History of stroke or intracranial hemorrhage within 6 months prior to enrollment
  • Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or put the study at risk
  • Received anticoagulation therapy with Coumadin or equivalent vitamin K antagonists within the last 28 days
  • Vaccinated with live, attenuated vaccines with 4 weeks of first does of study drug
  • Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4), grade =< 1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia
  • Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
  • Unwilling or unable to participate in all required study evaluations and procedures
  • Currently active, clinically significant hepatic impairment >= moderate hepatic impairment according to the National Cancer Institute (NCI)/Child Pugh classification

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase I Study Combining Ibrutinib With Rituximab, Ifosfamide, Carboplatin, and Etoposide (R-ICE) in Patients With Relapsed or Primary Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

This phase I trial studies the side effects and best dose of ibrutinib when given together with rituximab, ifosfamide, carboplatin, and etoposide (combination chemotherapy) in treating patients with diffuse large B-cell lymphoma (DLBCL) that has returned after a period of improvement (relapsed) or has not responded to treatment (refractory). Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as, rituximab, ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ibrutinib together with combination chemotherapy may be a better treatment for patients with relapsed or refractory DLBCL.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Safety of ibrutinib in combination with rituximab-ifosfamide, carboplatin, and etoposide (R-ICE).

II. Establishment of maximum tolerated dose of ibrutinib with R-ICE.

SECONDARY OBJECTIVES:

  1. Pharmacokinetic (PK) studies of ibrutinib in combination with R-ICE. II. Clinical response rate of ibrutinib+R-ICE.

OUTLINE: This is a dose-escalation study of ibrutinib.

Patients receive ibrutinib orally (PO) once daily (QD) on days 1-21, rituximab intravenously (IV) on day 1, ifosfamide IV on day 3, carboplatin intravenously piggy back (IVPB) on day 3, and etoposide IVPB on days 2-4. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 52 weeks.

Being tested
Carboplatin, Etoposide, Ibrutinib, Ifosfamide, Laboratory Biomarker Analysis
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

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

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IVPB

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given IVPB

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

    Given PO

  • IfosfamideDrug

    Also called Asta Z 4942, Asta Z-4942, Cyfos, Holoxan

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

Study groups in NCT02219737
Study groupRoleWhat they receive
Treatment (ibrutinib, R-ICE)ExperimentalPatients receive ibrutinib PO QD on days 1-21, rituximab IV on day 1, ifosfamide IV on day 3, carboplatin IVPB on day 3, and etoposide IVPB on days 2-4. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Carboplatin; Drug: Etoposide; Drug: Ibrutinib; Drug: Ifosfamide; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Rituximab

What is being measured

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

  1. Maximum tolerated dose of the combination of ibrutinib with standard dosing R-ICE, graded using the Common Terminology Criteria for Adverse Events 4.0

    Measured: Day 21

  2. Toxicity of the combination of ibrutinib with standard dosing R-ICE, graded using the CTCAE 4.0

    Measured: Up to week 52

Secondary outcomes (2)

  1. Overall response rate, defined as the sum of partial and complete responses as determined by revised International Working Group Criteria for Malignant Lymphoma

    The proportion of patients who achieve a clinical response (partial response or better) will be estimated in this patient population. This will be calculated among patients who receive any study drug, and additionally among patients who complete three cycles of therapy.

    Measured: Up to week 52

  2. PK parameters of ibrutinib in the presence of R-ICE as a measure of potential drug-drug interaction

    Measured: Predose, 30 minutes, 1, 2, 3, 4, 6, 8, 10 (optional), and 24 hours on day 15 (course 1) and day 1 (course 2)

Timeline

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

  1. First posted19 Aug 2014 (estimated)
  2. Study start12 Sep 2014
  3. Primary completion11 May 2017
  4. Study completion11 May 2017

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
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02219737
Sponsor's protocol ID
NCI-2014-00571
Other IDs
NCI-2014-00571, 14-145, 9588, 9588, P30CA008748
Status last verified
Jan 2018
First submitted
16 Jul 2014
Last updated
26 Jan 2018
Results posted
No
Data monitoring committee
No

Publications

  • Sauter CS, Matasar MJ, Schoder H, Devlin SM, Drullinsky P, Gerecitano J, Kumar A, Noy A, Palomba ML, Portlock CS, Straus DJ, Zelenetz AD, McCall SJ, Miller ST, Courtien AI, Younes A, Moskowitz CH. A phase 1 study of ibrutinib in combination with R-ICE in patients with relapsed or primary refractory DLBCL. Blood. 2018 Apr 19;131(16):1805-1808. doi: 10.1182/blood-2017-08-802561. Epub 2018 Jan 31.

    PubMed 29386196

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Carboplatin, Etoposide and Ibrutinib in people with CD20 Positive and Recurrent Diffuse Large B-Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.

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 20 inclusion and 27 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 26 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

Maximum tolerated dose of the combination of ibrutinib with standard dosing R-ICE, graded using the Common Terminology Criteria for Adverse Events 4.0 (time frame: Day 21). The study lists 2 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 NCT02219737, 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 26 Jan 2018.

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