Clinical Trials /

Split-Dose R-CHOP for Older Adults With DLBCL

NCT03943901

Description:

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).

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • High Grade B-Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
  • Transformed Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Split-Dose R-CHOP for Older Adults With DLBCL
  • Official Title: A Phase II Study of Split-Dose R-CHOP in Older Adults With Diffuse Large B-cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: UW18131
  • SECONDARY ID: 2019-0138
  • SECONDARY ID: SMPH\MEDICINE\HEM-ONC
  • SECONDARY ID: A534260
  • NCT ID: NCT03943901

Conditions

  • Diffuse Large B Cell Lymphoma
  • DLBCL
  • Cancer

Interventions

DrugSynonymsArms
RituximabRituxanSplit Dose R-CHOP
CyclophosphamideCytoxanSplit Dose R-CHOP
DoxorubicinAdriamycinSplit Dose R-CHOP
VincristineSplit Dose R-CHOP
PrednisoneSplit Dose R-CHOP
PegfilgrastimfilgrastimSplit Dose R-CHOP

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Split Dose R-CHOPExperimentalEach 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.
  • Rituximab
  • Cyclophosphamide
  • Doxorubicin
  • Vincristine
  • Prednisone
  • Pegfilgrastim

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

          -  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
             μmol/L 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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:70 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Response Rate (CR)
Time Frame:up to 6 months
Safety Issue:
Description: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

Measure:Progression Free Survival (PFS)
Time Frame:up to 2 years 6 months
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:up to 2 years 6 months
Safety Issue:
Description: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.
Measure:Incidence of Treatment Emergent Adverse Events
Time Frame:up to 2 years 6 months
Safety Issue:
Description: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.
Measure:Cancer-Specific Geriatric Assessment
Time Frame:up to 2 years 6 months
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Wisconsin, Madison

Trial Keywords

  • chemotherapy
  • cancer
  • elderly
  • lymphoma

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