A Phase 1 interventional study of Autologous Hematopoietic Stem Cell Transplantation and Avelumab in Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Mantle Cell Lymphoma and Refractory Diffuse Large B-Cell Lymphoma, sponsored by City of Hope Medical Center. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-12.
Sponsored by City of Hope Medical Center · Phase 1, Interventional, and Treatment
This phase I trial studies the side effects and best dose of avelumab, utomilumab, rituximab, ibrutinib, and combination chemotherapy in treating patients with diffuse large B-cell lymphoma or mantle cell lymphoma that has come back or does not respond to treatment. Monoclonal antibodies, such as avelumab, utomilumab, and rituximab, may interfere with the ability of tumor cells to grow and spread. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as etoposide phosphate, carboplatin, and ifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving avelumab, utomilumab, rituximab, ibrutinib, and combination chemotherapy may work better in treating patients with diffuse large B-cell lymphoma or mantle cell lymphoma.
PRIMARY OBJECTIVES:
I. Evaluate the safety and tolerability of the combination of avelumab (Ave) plus utomilumab (Uto) plus rituximab, ifosfamide, carboplatin, and etoposide phosphate (RICE) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) as first (1st) line salvage therapy.
II. Evaluate the safety and tolerability of Ave plus Uto plus rituximab (R)/ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL).
III. Determine the maximum tolerated dose (MTD) of the combination of Ave plus Uto with RICE for DLBCL.
IV. Determine the MTD of the combination of Ave plus Uto with R/ibrutinib for MCL.
SECONDARY OBJECTIVES:
I. Estimate overall response rate (ORR), complete response (CR) rate, duration of response (DOR), and progression-free survival (PFS) of the combination therapy.
II. Evaluate the stem cell mobilization rate after Ave+Uto+RICE therapy in DLBCL patients.
EXPLORATORY OBJECTIVES I. Explore immunologic and genomic biomarkers of response to Ave+Uto-based combination therapy.
II. Explore the use of CCND1 messenger (m)ribonucleic acid (RNA) for minimal residual disease (MRD) monitoring for MCL.
OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients receive rituximab intravenously (IV) on day 1, etoposide phosphate IV on days 1-3, avelumab IV over 60 minutes on day 2, ifosfamide IV over 24 hours on day 2, and carboplatin IV on day 2 or rituximab IV on day 1, etoposide phosphate IV on days 1-3, avelumab IV over 60 minutes on days 2, utomilumab IV over 60 minutes on day 2, ifosfamide IV over 24 hours on day 2, and carboplatin IV on day 2. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients may then undergo autologous hematopoietic stem cell transplantation.
COHORT II: Patients receive rituximab IV on day 1, avelumab IV over 60 minutes on days 2 and 16, and ibrutinib orally (PO) once daily (QD) or rituximab IV on day 1, avelumab IV over 60 minutes on days 2 and 16, utomilumab IV on day 2, and ibrutinib PO QD. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. (Closed as of 12/12/2019)
After completion of study treatment, patients in cohort I are followed up for up to 3 months or 2 years and patients in cohort II are followed up at 30 and 90 days and then every 6 months for up to 2 years.
Absolute neutrophil count (ANC) >= 1,000/mm\^3 (performed within 14 days prior to day 1 of protocol therapy)
Platelets >= 50,000/mm\^3 for MCL cohort and platelets >= 75,000/mm\^3 for DLBCL cohort (performed within 14 days prior to day 1 of protocol therapy)
If not receiving anticoagulants: international normalized ratio (INR) OR prothrombin (PT) =\< 1.5 x ULN (performed within 14 days prior to day 1 of protocol therapy)
If not receiving anticoagulants: activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (performed within 14 days prior to day 1 of protocol therapy)
Female of childbearing potential: negative urine or serum pregnancy test, performed within 14 days prior to day 1 of protocol therapy
Exclusion Criteria:
Patients receive rituximab IV on day 1, etoposide phosphate IV on days 1-3, avelumab IV over 60 minutes on day 2, ifosfamide IV over 24 hours on day 2, and carboplatin IV on day 2 or rituximab IV on day 1, etoposide phosphate IV on days 1-3, avelumab IV over 60 minutes on days 2, utomilumab IV over 60 minutes on day 2, ifosfamide IV over 24 hours on day 2, and carboplatin IV on day 2. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients may then undergo autologous hematopoietic stem cell transplantation.
Procedure: Autologous Hematopoietic Stem Cell Transplantation · Drug: Avelumab · Drug: Carboplatin · Drug: Etoposide Phosphate · Drug: Ifosfamide · Other: Laboratory Biomarker Analysis · Biological: Rituximab · Biological: Utomilumab
Patients receive rituximab IV on day 1, avelumab IV over 60 minutes on days 2 and 16, and ibrutinib PO QD or rituximab IV on day 1, avelumab IV over 60 minutes on days 2 and 16, utomilumab IV on day 2, and ibrutinib PO QD. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. (Closed as of 12/12/2019)
Drug: Avelumab · Drug: Ibrutinib · Other: Laboratory Biomarker Analysis · Biological: Rituximab · Biological: Utomilumab
Undergo autologous hematopoietic stem cell transplantation
Also known as: AHSCT, Autologous Hematopoietic Cell Transplantation, autologous stem cell transplantation, Stem Cell Transplantation, Autologous
Given IV
Also known as: Bavencio, MSB-0010718C, MSB0010718C
Given IV
Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo
Given IV
Also known as: Etopophos
Given PO
Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765
Given IV
Also known as: Asta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942
Correlative studies
Given IV
Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima
Given IV
Also known as: PF 05082566, PF 5082566, PF-05082566, PF-2566
Maximum tolerated dose determined by dose-limiting toxicities
Time frame: Up to 21 days (cohort I) or 28 days (cohort II)
Incidence of adverse events
Will be evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Observed toxicities will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.03 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution.
Time frame: Up to 2 years
Overall response rate
Will be defined as the proportion of response-evaluable participants that have a documented complete response (CR) or partial response (PR) at any time. Will be estimated by the proportion of evaluable patients achieving either CR or PR, along with the 95% exact binomial confidence interval.
Time frame: Up to 2 years
CR rate
Will be defined as the proportion of response-evaluable participants that have a documented CR at any time. Will be estimated by the proportion of evaluable patients achieving CR, along with the 95% exact binomial confidence interval.
Time frame: Up to 2 years
Duration of response
Will be defined as the duration from the time a patient first achieves CR or PR until the time that relapse or progressive disease is objectively documented. Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation.
Time frame: Up to 2 years
Progression-free survival
Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation.
Time frame: From start of treatment to time of disease progression or death due to any cause, whichever occurs first, assessed up to 2 years
Immunologic and genomic biomarkers
Standard descriptive methods will be used to summarize these biomarkers and their changes over time when available.
Time frame: Up to 2 years
This study is completed, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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Lymphoma, Large B-Cell, Diffuse→
City of Hope Medical Center