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Drug Interventions

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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/21/2021.

Split-Dose R-CHOP for Older Adults With DLBCL

Clinicaltrials.gov identifier NCT03943901

Recruitment Status Not yet recruiting

First Posted May 9, 2019

Last update posted September 3, 2020

Study Description

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:Diffuse Large B Cell Lymphoma
    DLBCL
    Cancer
  • Intervention/Treatment: Drug: Rituximab
    Drug: Cyclophosphamide
    Drug: Doxorubicin
    Drug: Vincristine
    Drug: Prednisone
    Biological: Pegfilgrastim
  • Phase: 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.

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 46 participants
  • 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
  • Estimated Study Start Date: October 2020
  • Estimated Primary Completion Date: September 2021
  • Estimated Study Completion Date: September 2022
Arms and interventions
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 Cyclophosphamide 375 mg/m2 IV Doxorubicin 25 mg/m2 IV Vincristine 1 mg IV Prednisone 50 mg (Days 1-5) PO Pegfilgrastim 6 mg on Day 2 (24 hours after completion of chemotherapy) or filgrastim daily for a minimum of 7 days (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 6 mg on Day 16 (24 hours after completion of chemotherapy) or Filgrastim daily for a minimum of 7 days (starting 24 hours post completion of chemotherapy), or institutional standard granulocyte stimulating factor.
Drug: Rituximab
Rituximab is a monoclonal antibody

Drug: Cyclophosphamide
Chemotherapy drug, alkylating agent

Drug: Doxorubicin
Chemotherapy drug, anthracycline antibiotic

Drug: Vincristine
Chemotherapy drug, plant alkaloid

Drug: Prednisone
Steroid, anti-inflammatory

Biological: Pegfilgrastim
Granulocyte stimulating factor, biologic response modifier
Outcome Measures
  • 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.
Eligibility Criteria
  • Ages Eligible for Study: 70 Years and older (Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
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

- 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 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

- 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

Contacts and Locations
Contacts

Contact: Cancer Connect 800-622-8922 clinicaltrials@cancer.wisc.edu

Locations

United States, Wisconsin
University of Wisconsin Carbone Cancer Center
Madison

Sponsors and Collaborators

University of Wisconsin, Madison

Medical College of Wisconsin

Investigators

Principal Investigator: Christopher Fletcher, MD University of Wisconsin, Madison

Study Chair: Nirav Shah, MD, MS Medical College of Wisconsin Clinical Cancer Center

More Information
  • Responsible Party: University of Wisconsin, Madison
  • ClinicalTrials.gov Identifier: NCT03943901 History of Changes
  • Other Study ID Numbers: UW18131, 2019-0138, SMPH\MEDICINE\HEM-ONC, A534260, Protocol Version 2/20/2020
  • First Posted: May 9, 2019 Key Record Dates
  • Last Update Posted: September 3, 2020
  • Last Verified: August 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: No
  • 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: chemotherapy
    cancer
    elderly
    lymphoma
  • Additional relevant MeSH terms: Lymphoma
    Lymphoma, B-Cell
    Lymphoma, Large B-Cell, Diffuse