split-dose r-chop for older adults with dlbcl

Conditions: Diffuse Large B Cell Lymphoma; DLBCL; Cancer

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).

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.

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

Keywords: chemotherapy cancer elderly lymphoma