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Split-Dose R-CHOP for Older Adults With DLBCL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03943901
Recruitment Status : Recruiting
First Posted : May 9, 2019
Last Update Posted : December 13, 2022
Medical College of Wisconsin
Information provided by (Responsible Party):
University of Wisconsin, Madison

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).

Condition or disease Intervention/treatment Phase
Diffuse Large B Cell Lymphoma DLBCL Cancer Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Biological: Pegfilgrastim Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Split-Dose R-CHOP in Older Adults With Diffuse Large B-cell Lymphoma
Actual Study Start Date : February 16, 2021
Estimated Primary Completion Date : April 2024
Estimated Study Completion Date : October 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: 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.
Drug: Rituximab
Rituximab is a monoclonal antibody
Other Name: Rituxan

Drug: Cyclophosphamide
Chemotherapy drug, alkylating agent
Other Name: Cytoxan

Drug: Doxorubicin
Chemotherapy drug, anthracycline antibiotic
Other Name: Adriamycin

Drug: Vincristine
Chemotherapy drug, plant alkaloid

Drug: Prednisone
Steroid, anti-inflammatory

Biological: Pegfilgrastim
Granulocyte stimulating factor, biologic response modifier
Other Name: filgrastim

Primary Outcome Measures :
  1. Complete Response Rate (CR) [ Time Frame: up to 6 months ]
    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.

Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: up to 2 years 6 months ]
    PFS measures survival without relapse/progression or death starting from study enrollment. Relapse or progression of disease and death will be considered as events; subjects who survive without recurrence or progression will be censored at last contact. PFS will be estimated using the Kaplan Meier estimate and presented with graphically with pointwise 95% confidence intervals.

  2. Overall Survival (OS) [ Time Frame: up to 2 years 6 months ]
    OS measures time to death starting from study enrollment. Death from any cause will be considered an event; surviving subjects will be censored at time of last follow-up. OS will be estimated using the Kaplan-Meier estimate and presented with graphically with pointwise 95% confidence intervals. Exploratory Cox proportional hazards regression will be used to evaluate the effect of baseline covariates on PFS and OS.

  3. Incidence of Treatment Emergent Adverse Events [ Time Frame: up to 2 years 6 months ]
    The incidence of serious adverse events will be reported for all subjects who received at least one dose of the study treatment. The proportion of subjects experiencing a Serious Adverse Event (SAE) will be reported with 95% confidence intervals overall, as well as classified by grade and organ system. Toxicity will be monitored using the formal boundary described in the protocol.

  4. Cancer-Specific Geriatric Assessment [ Time Frame: up to 2 years 6 months ]
    Cancer-specific geriatric assessment prior to, during, and after completion of chemotherapy treatments to evaluate for changes in physical function, mental health, cognition, and other relevant geriatric specific outcomes. The geriatric assessment measures will be summarized descriptively at each measurement time-point using appropriate descriptive statistics such as frequencies and percentages with standard errors for categorical variables, mean with standard error or median with quartiles for continuous variables.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   70 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03943901

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Contact: Cancer Connect 800-622-8922

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United States, Wisconsin
University of Wisconsin Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53705
Contact: Cancer Connect    800-622-8922   
Principal Investigator: Christopher D Fletcher, MD         
Sponsors and Collaborators
University of Wisconsin, Madison
Medical College of Wisconsin
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Principal Investigator: Christopher Fletcher, MD University of Wisconsin, Madison
Study Chair: Nirav Shah, MD, MS Medical College of Wisconsin Clinical Cancer Center
Additional Information:
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Responsible Party: University of Wisconsin, Madison Identifier: NCT03943901    
Other Study ID Numbers: UW18131
2019-0138 ( Other Identifier: Institutional Review Board )
SMPH\MEDICINE\HEM-ONC ( Other Identifier: UW Madison )
A534260 ( Other Identifier: UW Madison )
Protocol Version 6/14/2022 ( Other Identifier: UW Madison )
NCI-2020-01530 ( Registry Identifier: NCI Trial ID )
First Posted: May 9, 2019    Key Record Dates
Last Update Posted: December 13, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Wisconsin, Madison:
Additional relevant MeSH terms:
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Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents