Ibrutinib and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma
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)
4 other identifiers
interventional
26
1 country
1
Brief 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 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Sep 2014
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 16, 2014
CompletedFirst Posted
Study publicly available on registry
August 19, 2014
CompletedStudy Start
First participant enrolled
September 12, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 11, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
May 11, 2017
CompletedJanuary 26, 2018
January 1, 2018
2.7 years
July 16, 2014
January 25, 2018
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum tolerated dose of the combination of ibrutinib with standard dosing R-ICE, graded using the Common Terminology Criteria for Adverse Events 4.0
Day 21
Toxicity of the combination of ibrutinib with standard dosing R-ICE, graded using the CTCAE 4.0
Up to week 52
Secondary Outcomes (2)
Overall response rate, defined as the sum of partial and complete responses as determined by revised International Working Group Criteria for Malignant Lymphoma
Up to week 52
PK parameters of ibrutinib in the presence of R-ICE as a measure of potential drug-drug interaction
Predose, 30 minutes, 1, 2, 3, 4, 6, 8, 10 (optional), and 24 hours on day 15 (course 1) and day 1 (course 2)
Study Arms (1)
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.
Interventions
Given IVPB
Given IVPB
Given PO
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- 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:
- or more clearly demarcated lesions/nodes with a long axis \> 1.5 cm and short axis \>= 1.0 cm OR
- 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:
- 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 Ă— institutional upper limit of normal (unless due to lymphoma involvement of liver)
- +5 more criteria
You may not qualify if:
- 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
- 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
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
Related Publications (1)
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.
PMID: 29386196DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Craig Sauter
Memorial Sloan Kettering Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 16, 2014
First Posted
August 19, 2014
Study Start
September 12, 2014
Primary Completion
May 11, 2017
Study Completion
May 11, 2017
Last Updated
January 26, 2018
Record last verified: 2018-01