Split-Dose R-CHOP for Older Adults With DLBCL

NCT ID: NCT03943901

Last Updated: 2025-03-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-17
• Study Completion Date: 2027-02-28

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).

Detailed Description

This study will test the efficacy of split-dose R-CHOP for the treatment of elderly patients with de novo diagnosis of DLBCL or transformed DLBCL. Split-dose R-CHOP involves giving Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) chemotherapy at 14 days' interval with Rituximab given once/month. The safety for every 14-day CHOP administration was studied in a large prospective randomized control trial of patients up to the age of 80 years. In this study, R-CHOP given every 14 days for up to 6 cycles was felt to be the best method of delivery of chemotherapy. Receiving greater than 6 cycles of R-CHOP chemotherapy was not found to be beneficial compared to participants receiving 6 cycles of R-CHOP. Additionally, an interim response adapted approach by combining imaging and MRD testing will be used to identify participants who will receive an abbreviated chemotherapy course if they are both Positron Emission Tomography/Computed Tomography (PET/CT) and Minimum Residual Dose (MRD) negative.

In the proposed study, participants will receive a 50% dose reduction of CHOP chemotherapy on Day 1 and Day 15 of each cycle with full dose Rituximab on Day 1 for up to a total of 6 months of chemotherapy. Participants who are MRD and PET/CT negative after 2 months will be placed on an abbreviated regimen with R-CHOP x 4 additional doses with full dose Rituximab and a 50% dose reduction in CHOP chemotherapy. The hypothesis is that this method of administration of R-CHOP will be a safe and effective form of chemotherapy for older patients with DLBCL and will allow older patients to receive curative intent treatment.

Conditions

Diffuse Large B Cell Lymphoma; DLBCL; Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Split Dose R-CHOP

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.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

Rituximab is a monoclonal antibody

Cyclophosphamide

Intervention Type: DRUG

Chemotherapy drug, alkylating agent

Doxorubicin

Intervention Type: DRUG

Chemotherapy drug, anthracycline antibiotic

Vincristine

Intervention Type: DRUG

Chemotherapy drug, plant alkaloid

Prednisone

Intervention Type: DRUG

Steroid, anti-inflammatory

Pegfilgrastim

Intervention Type: BIOLOGICAL

Granulocyte stimulating factor, biologic response modifier

Interventions

Rituximab

Rituximab is a monoclonal antibody

Intervention Type: DRUG

Cyclophosphamide

Chemotherapy drug, alkylating agent

Intervention Type: DRUG

Doxorubicin

Chemotherapy drug, anthracycline antibiotic

Intervention Type: DRUG

Vincristine

Chemotherapy drug, plant alkaloid

Intervention Type: DRUG

Prednisone

Steroid, anti-inflammatory

Intervention Type: DRUG

Pegfilgrastim

Granulocyte stimulating factor, biologic response modifier

Intervention Type: BIOLOGICAL

Other Intervention Names

Rituxan; Cytoxan; Adriamycin; filgrastim

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical College of Wisconsin

OTHER

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher Fletcher, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Nirav Shah, MD, MS

Role: STUDY_CHAIR

Medical College of Wisconsin Clinical Cancer Center

Locations

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Countries

United States

Related Links

https://cancer.wisc.edu

University of Wisconsin Carbone Cancer Center

Other Identifiers

2019-0138

Identifier Type: OTHER

Identifier Source: secondary_id

SMPH\MEDICINE\HEM-ONC

Identifier Type: OTHER

Identifier Source: secondary_id

A534260

Identifier Type: OTHER

Identifier Source: secondary_id

Protocol Version 7/21/2023

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2020-01530

Identifier Type: REGISTRY

Identifier Source: secondary_id

UW18131

Identifier Type: -

Identifier Source: org_study_id