Ibrutinib in Combination With Lenalidomide and Rituximab in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Status and phase
Completed
Phase 2
Phase 1
Conditions
Relapsed Diffuse Large B-Cell Lymphoma
Refractory Diffuse Large B-Cell Lymphoma
Treatments
Drug: Ibrutinib
Drug: Rituximab
Drug: Lenalidomide
Study type
Interventional
Funder types
Industry
Identifiers
Details and patient eligibility
About
This Phase 1b/2 study is designed to assess the safety and efficacy of ibrutinib in combination with lenalidomide and rituximab in subjects with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not eligible for transplant.
Full description
Phase 1b: In the dose escalation portion of the study, various cohorts with escalating doses of lenalidomide may be explored, using the 3+3+3 principle for dose determination.
Phase 2: This will be conducted as an international, multicenter, open-label study. Eligible subjects will receive ibrutinib, lenalidomide and rituximab.
Enrollment
138 patients
Sex
All
Ages
18+ years old
Volunteers
No Healthy Volunteers
Inclusion criteria
- Pathologically confirmed relapsed/ refractory DLBCL
- Must have previously received first line treatment regimen
- Must be ineligible for high dose therapy/ stem cell transplantation
- Measurable disease sites on computed tomography (CT) scan (>1.5 cm in longest dimension)
- prothrombin time/international normalized ratio (PT/INR) < 1.5 x upper limit of normal (ULN) and partial thromboplastin time (PTT; activated partial thromboplastin time [aPTT]) <1.5 x ULN
- Men and women ≥18 years of age
- Eastern Cooperative Oncology Group (ECOG) < 2
- Adequate hepatic and renal function
- Adequate hematologic function
Exclusion criteria
- Medically apparent central nervous system lymphoma or leptomeningeal disease
- History of allogeneic stem-cell (or other organ) transplantation
- Any chemotherapy, external beam radiation therapy, or anticancer antibodies within 2 weeks
- Radio- or toxin-immunoconjugates within 10 weeks
- Concurrent enrollment in another therapeutic investigational study or have previously taken ibrutinib and/or lenalidomide.
Trial design
Primary purpose
Treatment
Allocation
Non-Randomized
Interventional model
Sequential Assignment
Masking
None (Open label)
138 participants in 7 patient groups
Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1)
Experimental group
Description:
Ibrutinib 560 mg administered orally (PO) once daily (QD) beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 15 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered intravenously (IV) on Day 1 of each 28-day cycle for 6 cycles.
Treatment:
Drug: Rituximab
Drug: Lenalidomide
Drug: Ibrutinib
Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1)
Experimental group
Description:
De-escalation cohort: Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 10 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles.
Treatment:
Drug: Rituximab
Drug: Lenalidomide
Drug: Ibrutinib
Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+)
Experimental group
Description:
Re-escalation cohort: Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 15 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles.
Treatment:
Drug: Rituximab
Drug: Lenalidomide
Drug: Ibrutinib
Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2)
Experimental group
Description:
Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 20 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles.
Treatment:
Drug: Rituximab
Drug: Lenalidomide
Drug: Ibrutinib
Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3)
Experimental group
Description:
Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 25 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles.
Treatment:
Drug: Rituximab
Drug: Lenalidomide
Drug: Ibrutinib
Phase 2: Enrolled at Lenalidomide Dose 20 mg
Experimental group
Description:
Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 20 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles.
Treatment:
Drug: Rituximab
Drug: Lenalidomide
Drug: Ibrutinib
Phase 2: Enrolled at Lenalidomide Dose 25 mg
Experimental group
Description:
Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 25 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles.
Treatment:
Drug: Rituximab
Drug: Lenalidomide
Drug: Ibrutinib
Trial contacts and locations
40
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Data sourced from clinicaltrials.gov
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