Neoplasms

Blood and Lymph Conditions

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All Conditions

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Rare Diseases

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Aggression

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Amino Acids

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Acalabrutinib

Rituximab

Vincristine

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

6x R-miniCHOP + 2x Rituximab + Acalabrutinib.

* Rituximab i.v.: 375 mg/m2 (D0)
* Cyclophosphamide i.v.: 400 mg/m² (D1)
* Doxorubicin i.v.: 25 mg/m² (D1)
* Vincristine i.v.: 1 mg (D1)
* Prednisolone p.o.: 40 mg/m² (D1 to D5)
* Acalabrutinib 100 mg p.o. twice daily starting from D1 of first R-miniCHOP cycle continuously to D21 of cycle 8.

Cycles repeated every 3 weeks

R-miniCHOP + Acalabrutinib

* Rituximab i.v.: 375 mg/m2 (D0)
* Cyclophosphamide i.v.: 400 mg/m² (D1)
* Doxorubicin i.v.: 25 mg/m² (D1)
* Vincristine i.v.: 1 mg (D1)
* Prednisolone p.o.: 40 mg/m² (D1 to D5).

Cycles repeated every 3 weeks

R-miniCHOP

Konstantinos Christofyllakis, MD MSc

Manfred Welslau, MD

Börge Arndt, MD

Kristina LErch, MD

Thomas Illmer, MD

Mathias Rummel, Prof MD

Christian Andreas Schmidt, Prof. MD

Franziska Brunner, MD

Martin Bentz, Prof. MD

Kai Wille, MD

Ulf Reinhart, MD

Tobias Gaska, MD

Julian Topaly, MD, PD

Rolf Mahlberg, MD

Heinz Kirchen, MD

Hanno Witte, MD

Andreas Viardot, Prof. MD

Moritz Bewarder, MD, PD

The goal of this clinical trial is to study the addition of Acalabrutinib to standard R-miniCHOP in older adults with DLBCL. The main question it aims to answer is whether progression free survival kann be prolonged with the addition of Acalabrutinib.

Participants will be randomised to receive either R-miniCHOP alone or R-miniCHOP with Acalabrutinib.

Acalabrutinib in Combination With R-miniCHOP in Older Adults With Untreated Diffuse Large B-Cell Lymphoma

A Randomized, Open-label, Phase 3 Study of Acalabrutinib in Combination With Rituximab and Reduced Dose CHOP (R-miniCHOP) in OldEr Adults With Untreated Diffuse Large B-Cell Lymphoma

PFS, defined by the time between the day of randomization until one of the following events occurs, whichever comes first: Disease progression (PD), relapse after complete remission (CR) or death due to any cause, as per Lugano Classification of 2014. Patients who have not experienced an event at the time of analysis will be censored at the most recent date of disease assessment.

OS, defined by the time between the day of randomization until death due to any cause. Patients who have not experienced an event at the time of analysis will be censored at the date when the patient was last known to be alive.

EFS, defined by the time between the day of randomization until one of the following events occurs, whichever comes first: Progressive disease (PD), relapse after complete remission (CR), initiation of subsequent systemic anti-lymphoma treatment and/or irradiation or death due to any cause, as per Lugano Classification of 2014.

University of Leipzig

University Hospital Regensburg

Wuerzburg University Hospital

University Hospital of Gießen and Marburg

Saarland University Medical Center

AstraZeneca

Universität des Saarlandes

Anti-Infective Agents

Obinutuzumab

Prednisone

Ibrutinib

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Patients will receive a maximum of 6 courses of G-CHOP-21 followed by 2 doses of Obinutuzumab in combination with Ibrutinib.

Patients will receive a maximum of 6 courses of CHOP-21 in combination with Obinutuzumab (G) followed by 2 doses of Obinutuzumab in combination with Ibrutinib.

CHOP

Maurizio Martelli, MD

This is a prospective, multicenter, single arm, phase II trial in young patients (18-60 years) with poor-prognosis (aaIPI 2 or 3) newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL).

Aim of the study is to assess the efficacy and the safety of G-CHOP in combination with ibrutinib.

This is a prospective, multicenter, single arm, phase II trial in young patients (18-60 years) with poor-prognosis (age-adjusted International Prognostic Index, aaIPI, 2 or 3) newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL).

Patient will receive 6 courses of G-CHOP21 (Obimutizumab- cyclophosphamide, hydroxydaunomycin, Oncovin, and prednisone) followed by 2 doses of Obinutuzumab supplemented with Ibrutinib. Duration of treatment will be 5 months plus 4-5 weeks for response evaluation.

During the study, disease status will be evaluated after the 4th cycle by computed tomography (CT) scan, and after end of treatment by imaging test (18FDG-PET \[positron emission tomography\] and CT scan).

Patients will be recruited over 2 years and followed for a minimum of 2 years after the end of the treatment phase.

Phase II Study About Combination CHOP-21, Obinutuzumab and Ibrutinib in Untreated Young High Risk DLBCL Patients.

Multicenter Phase II Single Arm Open-label Study on the Feasibility, Safety and Efficacy of Combination of CHOP-21 Supplemented With Obinutuzumab and Ibrutinib in Untreated Young High Risk Diffuse Large B-cell Lymphoma (DLBCL) Patients.

Fondazione Italiana Linfomi - ETS

Etoposide

Lenograstim

Etoposide phosphate

Patients receive the following treatment:Rituximab 375 mg/m2 IV infusion on Day 1 prior to CHOP chemotherapy.Cyclophosphamide 750 mg/m\^2 IV on Day 1.Doxorubicin 50 mg/m\^2 IV on Day 1.Vincristine 1.4 mg/m\^2 IV (2 mg cap) on Day 1.Prednisone 40 mg/m\^2/day PO on Days 1-5.filgrastim or pegfilgrastim as defined in the protocol Required ancillary medications is administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6.

Interventions:-Biological: rituximab-Drug: cyclophosphamide-Drug: doxorubicin-Drug: vincristine-Drug: prednisone-Drug: filgrastim-Drug: pegfilgrastim

Patients receive the following treatment: Cycle 1 Doses:Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to EPOCH chemotherapy. Doxorubicin 10 mg/m\^2/day CIVI on Days 1-4.Etoposide 50 mg/m\^2/day CIVI on Days 1-4. Vincristine 0.4 mg/m\^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours). Cyclophosphamide 750 mg/m\^2 IV on Day 5 (following completion of 96 hour infusions). Prednisone 60 mg/m\^2 PO BID on Days 1-5 Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC \> 5000 after the nadir (nadir usually between Days 10-12) Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle. Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6.

Interventions:

-Biological: rituximab-Drug: cyclophosphamide-Drug: doxorubicin-Drug: vincristine-Drug: prednisone-Drug: etoposide-Drug: filgrastim

rituximab, etoposide, cyclophosphamide, doxorubicin, vincristine,prednisone, filgrastim

Ahmed Eltantawy, Master

This randomized phase II trial is studying two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell lymphoma.

objectives:

1. To compare the response rates and toxicity of R-CHOP versus DA-EPOCH-R in untreated CD20+ diffuse large B-cell lymphomas.
2. To compare the event-free survival of R-CHOP versus DA-EPOCH-R chemotherapy in untreated CD20+ diffuse large B-cell lymphomas.
3. To develop predictors of outcome of R-CHOP and DA-EPOCH-R chemotherapy.

Risk Adapted Therapy in Diffuse Large B Cell Lymphoma

Phase II Randomized Study of R-CHOP V. Dose-Adjusted EPOCH-R in Untreated De Novo Diffuse Large B-Cell Lymphomas

Mansoura University

Patients receive the following treatment:

* Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to CHOP chemotherapy
* Cyclophosphamide 750 mg/m\^2 IV on Day 1
* Doxorubicin 50 mg/m\^2 IV on Day 1
* Vincristine 1.4 mg/m\^2 IV (2 mg cap) on Day 1
* Prednisone 40 mg/m\^2/day PO on Days 1-5
* filgrastim or pegfilgrastim as defined in the protocol

Required ancillary medications is administered during all cycles as defined in the protocol.

Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6.

Patients receive the following treatment:

Cycle 1 Doses:

* Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to EPOCH chemotherapy
* Doxorubicin 10 mg/m\^2/day CIVI on Days 1-4
* Etoposide 50 mg/m\^2/day CIVI on Days 1-4
* Vincristine 0.4 mg/m\^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours)
* Cyclophosphamide 750 mg/m\^2 IV on Day 5 (following completion of 96 hour infusions)
* Prednisone 60 mg/m\^2 PO BID on Days 1-5
* Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC \> 5000 after the nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not being monitored, during every cycle.

Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle.

Required ancillary medications are administered during all cycles as defined in the protocol.

Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6.

rituximab

cyclophosphamide

doxorubicin

vincristine

prednisone

etoposide

filgrastim

pegfilgrastim

Wyndham H. Wilson, MD, PhD

Andrew D. Zelenetz, MD, PhD

This randomized phase III trial studies rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell non-Hodgkin's lymphoma. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy 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 rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective when given with rituximab in treating diffuse large B-cell non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell lymphoma.

PRIMARY OBJECTIVES:

I. To compare the event-free survival of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone (R-CHOP) versus dose-adjusted (DA-) etoposide, prednisone, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, and rituximab (EPOCH-R) chemotherapy in untreated cluster of differentiation (CD)20 positive (+) diffuse large B-cell lymphomas.

II. To develop a molecular predictor of outcome of R-CHOP and DA-EPOCH-R chemotherapy using molecular profiling.

SECONDARY OBJECTIVES:

I. To compare the response rates, overall survival and toxicity of R-CHOP versus DA-EPOCH-R.

II. To define the pharmacogenomics of untreated diffuse large B-cell lymphoma (DLBCL) and correlate clinical parameters (toxicity, response, survival outcomes and laboratory results) with molecular profiling.

III. To assess the use of molecular profiling for pathological diagnosis. IV. To identify new therapeutic targets using molecular profiling. V. To perform a comprehensive analysis of somatic alterations to the tumor genome and to understand which genomic alterations are somatically acquired by the tumor and which are encoded in the germ line of the patient.

VI. To identify biomarkers of response to chemotherapy by fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging that are predictive of histopathologic remissions and survival in patients with stage I (mediastinal), II, III, or IV untreated DLBCL.

VII. To evaluate the use of semiquantitative measurements of FDG uptake in defining FDG-PET/CT based biomarkers of response to chemotherapy in patients with DLBCL.

VIII. To determine whether FDG-PET/CT measurements of tumor response after the second cycle of chemotherapy can predict clinical response.

IX. To establish a standardized protocol for FDG-PET/CT image acquisition. X. To determine additional FDG-PET/CT parameters (e.g., the ratio of tumor maximum standard uptake value \[SUVmax\] to liver SUVmean; SUVs corrected for body surface area and lean body mass; nuclear medicine physician's assessment) and evaluate their utility in refining FDG-PET/CT based biomarkers of response to therapy.

XI. To evaluate inter-institutional reproducibility of FDG-PET/CT measurements for this indication.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma

Phase III Randomized Study of R-CHOP V. Dose-Adjusted EPOCH-R With Molecular Profiling in Untreated De Novo Diffuse Large B-Cell Lymphomas

Progression-free survival (PFS) is defined as the time from randomization to progression, relapse, or death from any cause, whichever occurred first. Progression (PD) or Relapse\>

* ≥ 50% increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders.\>
* Appearance of any new lesion during or after completion of therapy.\>
* PET+ is not a criterion for progressive disease. Patients only with PET+ findings must have evidence of progression on CT or biopsy proven.\>

The PFS rate (percentage of participants who are alive and progression-free) at 2 and 5 years Kaplan Meier estimates and 95% Confidence Intervals are reported below.

The overall response rate is defined as the percentage of participants with a response (Complete Response or Partial Response)

Overall survival is defined as the time from randomization to death due to any cause. The overall survival (OS) rate (percentage of participants who are still alive) at 2 and 5 years Kaplan Meier estimates and 95% confidence intervals are reported below.

National Cancer Institute (NCI)

Alliance for Clinical Trials in Oncology

All participants are followed for survival (i.e. included in the All-cause mortality table). Participants who received at least one dose of treatment are evaluable for adverse events (i.e. included in the Serious AE and Other (Not Including Serious) AE tables).

Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6.

Arm A - R-CHOP

Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6.

Arm B - DA-EPOCH-R

Patients receive the following treatment:\>

* Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to CHOP chemotherapy\>
* Cyclophosphamide 750 mg/m\^2 IV on Day 1\>
* Doxorubicin 50 mg/m\^2 IV on Day 1\>
* Vincristine 1.4 mg/m\^2 IV (2 mg cap) on Day 1\>
* Prednisone 40 mg/m\^2/day PO on Days 1-5\>
* filgrastim or pegfilgrastim as defined in the protocol\> Required ancillary medications is administered during all cycles as defined in the protocol.\> Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6.

Patients receive the following treatment:\> Cycle 1 Doses:\>

* Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to EPOCH chemotherapy\>
* Doxorubicin 10 mg/m\^2/day CIVI on Days 1-4\>
* Etoposide 50 mg/m\^2/day CIVI on Days 1-4\>
* Vincristine 0.4 mg/m\^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours)\>
* Cyclophosphamide 750 mg/m\^2 IV on Day 5 (following completion of 96 hour infusions)\>
* Prednisone 60 mg/m\^2 PO BID on Days 1-5\>
* Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC \> 5000 after the \> nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not \> being monitored, during every cycle.\> Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle.\> Required ancillary medications are administered during all cycles as defined in the protocol.\> Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6.

Total

Number analyzed in row differs from overall due to missing data.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Eastern Cooperative Oncology Group PS Scale: 0)Fully active, able to carry on all pre-disease performance without restriction; 1)Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2)Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3)Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4)Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair.

The number analyzed in row differs from overall due to missing data.

ECOG Performance Status

Participants who completed the study in the Participant Flow are included in this analysis.

Nancy Bartlett, M.D.

2-year PFS

5-year PFS

Progression-Free Survival Rate at 2 and 5 Years

Response Rate

2-year OS rate

5-year OS rate

Overall Survival Rate at 2 and 5 Years

Whether the Gene Expression Signatures That Were Previously Associated With Survival Following CHOP Therapy Are Associated With Survival in Either of the Treatment Arms of the Prospective Trial

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Acalabrutinib in Combination With R-miniCHOP in Older Adults With Untreated Diffuse Large B-Cell Lymphoma	NCT05820841	Large B-cell Ly... Diffuse Large B...	R-miniCHOP + Ac... R-miniCHOP	61 Years -	Universität des Saarlandes
Phase II Study About Combination CHOP-21, Obinutuzumab and Ibrutinib in Untreated Young High Risk DLBCL Patients.	NCT02670317	Lymphoma, B-Cel...	Obinutuzumab Ibrutinib CHOP	18 Years - 60 Years	Fondazione Italiana Linfomi - ETS
Risk Adapted Therapy in Diffuse Large B Cell Lymphoma	NCT03188198	Large B Cell Ly...	rituximab, etop...	16 Years -	Mansoura University
Acalabrutinib in Combination With R-miniCHOP in Older Adults With Untreated Diffuse Large B-Cell Lymphoma	NCT05820841	Large B-cell Ly... Diffuse Large B...	R-miniCHOP + Ac... R-miniCHOP	61 Years -	Universität des Saarlandes
Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma	NCT00118209	Large B Cell Ly...	rituximab cyclophosphamid... doxorubicin vincristine prednisone etoposide filgrastim pegfilgrastim	18 Years -	Alliance for Clinical Trials in Oncology

Spots Global Cancer Trial Database for large b cell lymphoma