Split-Dose R-CHOP for Older Adults With DLBCL

NCT03943901 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 5 other identifiers: 2019-0138SMPH\MEDICINE\HEM-ONCA534260Protocol Version 7/21/2023NCI-2020-01530
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This study is investigating a new administration schedule of Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP) chemotherapy for participants with Diffuse Large B-Cell Lymphoma (DLBCL), focusing on an underserved elderly population (aged 75 and up; certain participants 70-74 may be eligible) that is often excluded from clinical trials. Participants can expect to be on study for 2.5 years (treatment for 6 months and 2 years of post treatment follow-up).

Conditions

Diffuse Large B Cell Lymphoma; DLBCL; Cancer

Keywords

chemotherapy; cancer; elderly; lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CR)

  Simon 2-stage design with complete response (CR) rate at the end of treatment as our primary outcome. 40% is an unacceptable boundary for complete response rate and 60% as an acceptable complete response rate. CR at the end of treatment, will be estimated as the observed proportion and presented with a 95% Wilson confidence interval.

  up to 6 months

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  up to 2 years 6 months

• Overall Survival (OS)

  up to 2 years 6 months

• Incidence of Treatment Emergent Serious Adverse Events

  up 6 months

• Summary of Treatment Emergent Serious Adverse Events by Grade and Organ System

  up 6 months

• Cancer-Specific Geriatric Assessment

  up to 2 years 6 months

Study Arms (1)

Split Dose R-CHOP

EXPERIMENTAL

Each cycle is 28 days and consists of one "A" treatment on Day 1 and one "B" treatment on Day 15 for 6 cycles Day 1 ("A" part of cycle) * Rituximab 375 mg/m2 IV (or biosimilars Ruxience or Truxima) * Cyclophosphamide 375 mg/m2 IV * Doxorubicin 25 mg/m2 IV * Vincristine 1 mg IV * Prednisone 50 mg (Days 1-5) PO * Pegfilgrastim (supportive care) 6 mg on Day 2 (24 hours after completion of chemotherapy) or filgrastim daily as institutionally indicated (starting 24 hours post completion of chemotherapy), or institutional standard granulocyte stimulating factor. Day 15 ("B" part of cycle) * Cyclophosphamide 375 mg/m2 IV * Doxorubicin 25 mg/m2 IV * Vincristine 1 mg IV * Prednisone 50 mg (Days 15-19) PO * Pegfilgrastim (supportive care) 6 mg on Day 16 (24 hours after completion of chemotherapy) or filgrastim daily as institutionally indicated (starting 24 hours post completion of chemotherapy), or institutional standard granulocyte stimulating factor.

Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Biological: Pegfilgrastim

Interventions

Vincristine DRUG

Chemotherapy drug, plant alkaloid

Split Dose R-CHOP

Rituximab DRUG

Rituximab is a monoclonal antibody

Also known as: Rituxan

Split Dose R-CHOP

Cyclophosphamide DRUG

Chemotherapy drug, alkylating agent

Also known as: Cytoxan

Split Dose R-CHOP

Doxorubicin DRUG

Chemotherapy drug, anthracycline antibiotic

Also known as: Adriamycin

Split Dose R-CHOP

Prednisone DRUG

Steroid, anti-inflammatory

Split Dose R-CHOP

Pegfilgrastim BIOLOGICAL

Granulocyte stimulating factor, biologic response modifier

Also known as: filgrastim

Split Dose R-CHOP

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Signed and dated informed consent document indicating that the participant (or legally acceptable representative) has been informed of all pertinent aspects of the trial
• All patients age ≥75 years and participants aged 70-74 years who are determined to be unfit or frail by Cumulative Illness Rating Score-Geriatrics (CIRS-G) scale
• For participants aged 70-74 years: CIRS-G score with 5-8 comorbid conditions scored 2 or ≥1 comorbidity scored 3-4. CIRS-G score is to be reviewed by the study PI prior to enrollment.
• Newly diagnosed, untreated, biopsy proven CD20 positive DLBCL (including high grade B-cell lymphoma \& T-cell/histiocytic rich large B-cell lymphoma). Participants with discordant bone marrow (i.e. involved by low-grade/indolent NHL) are eligible. Participants with transformed DLBCL from underlying low-grade disease are eligible. Participants with composite DLBCL and concurrent low-grade lymphoma are eligible.
• Copy of pathology report must be sent to coordinating site to confirm diagnosis for eligibility
• Participants with prior treatment for low grade NHL with non-anthracycline based regimens are eligible
• Measurable disease by PET/CT or Bone Marrow (BM) biopsy prior to enrollment
• Left ventricular ejection fraction ≥50% by resting echocardiography or resting Multi-gated acquisition (MUGA) scan
• Karnofsky Performance Score ≥50
• Ann Arbor Stage II bulky, III, or IV disease
• Minimum life expectancy greater than 3 months
• Negative HIV test
• For participants with hepatitis B virus antigen (HbsAg) or core antibody (HbcAb) seropositivity, participants must have a negative Hep B viral load and an appropriate prophylaxis plan must be in place during chemotherapy therapy treatment. For all participants that have Hep B core antibody positive, they should take entecavir prophylaxis (0.5 mg PO daily) until 1 year from completion of chemotherapy. Hep B viral load should be checked on these participants prior to starting chemotherapy and every 3 months thereafter if initial Hep B viral load is negative (+/- 1 week if chemotherapy cycle is delayed). If Hep B viral load is positive, Hepatology or Identification (ID) referral is recommended, and hepatitis B virus (HBV) viral load should be checked monthly
• For participants with hepatitis C Ab (HbcAb) positivity, a viral load must be checked and be negative for enrollment
• Intrathecal chemotherapy for central nervous system prophylaxis only can be given at the discretion of the primary oncologist

You may not qualify if:

• History of previous anthracycline exposure
• Central Nervous System (CNS) or meningeal involvement at diagnosis
• Creatinine Clearance \<25 mL/min by body surface area (BSA)-adjusted Cockroft-Gault
• Poor hepatic function, defined as total bilirubin concentration greater than 3.0 mg/dL or transaminases over 4 times the maximum normal concentration, unless these abnormalities are felt to be related to the lymphoma.
• Pulmonary dysfunction defined as \>2 L of oxygen required by nasal cannula to maintain peripheral capillary oxygen saturation (SpO2) ≥90% unless felt to be related to underlying lymphoma.
• Myocardial Infarction within 6 months of enrollment
• Active, uncontrolled infectious disease
• Known concurrent bone marrow malignancies (e.g. myelodysplastic syndrome) or poor bone-marrow reserve, defined as neutrophil count less than 1.5×10⁹/L or platelet count less than 100×10⁹/L, unless caused by bone-marrow infiltration with lymphoma
• History of a second concurrent active malignancy or prior malignancy which required chemotherapy treatment within the preceding 2 years
• Treatment with any investigational drug within 30 days before the planned first cycle of chemotherapy
• Unable or unwilling to sign consent

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Medical College of Wisconsin: collaborator

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53705, United States

Location

Related Links

• University of Wisconsin Carbone Cancer Center

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Neoplasms; Lymphoma

Interventions

Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; pegfilgrastim; Filgrastim

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Christopher Fletcher, MD
• Organization: UW School of Medicine and Public Health

cdfletcher@medicine.wisc.edu

(608) 263-3135

Study Officials

• Christopher Fletcher, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

• Nirav Shah, MD, MS

  Medical College of Wisconsin Clinical Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2019
• First Posted: May 9, 2019
• Study Start: February 17, 2021
• Primary Completion: January 13, 2025
• Study Completion (Estimated): February 1, 2027
• Last Updated: January 29, 2026
• Results First Posted: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)