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Phase 2 N=91 Randomized Treatment

Rituximab, Methotrexate, Vincristine Sulfate, Procarbazine Hydrochloride, and Cytarabine With or Without Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma

Chemotherapeutic Agent Toxicity · Cognitive/Functional Effects · Lymphoma · Neurotoxicity · Radiation Toxicity

Enrolled (actual)
91
Serious AEs
50.0%
Results posted
May 2021
Primary outcome: Primary: Progression-free Survival — 2.1; NA years — p=0.015

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Rituximab (Biological); Cytarabine (Drug); Methotrexate (Drug); Procarbazine (Drug); Vincristine (Drug); low-dose whole-brain radiation therapy (Radiation)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Radiation Therapy Oncology Group
Primary completion
Mar 2020

Outcome Measures

OutcomeResultp-value
PRIMARY
Progression-free Survival
2.1; NA 0.015 sig
SECONDARY
Overall Survival
NA; NA 0.48
SECONDARY
Percentage of Participants Experiencing Partial Response or Complete Response
83.3; 80.6
SECONDARY
Global Heath Status (GHS) Score of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
62.78; 54.90; 67.67; 64.58; 74.54; 75.35 0.005 sig
SECONDARY
Percentage of Participants With Neurocognitive Failure
31.6; 17.9 0.18
SECONDARY
Distribution of Participants by Highest Grade Adverse Event Related to Protocol Treatment
2; 3; 3; 6; 4; 5

Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as methotrexate, vincristine sulfate, procarbazine hydrochloride, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x rays to kill cancer cells. It is not yet know whether rituximab and combination chemotherapy are more effective when given with or without radiation therapy in treating patients with primary central nervous system lymphoma. PURPOSE: This randomized phase II trial studies how well giving rituximab and combination chemotherapy with or without radiation therapy works in treating patients with primary central nervous system lymphoma.

Eligibility Criteria

Inclusion Criteria

  • B-cell non-Hodgkin's lymphoma(NHL) involving the brain, as demonstrated by contrast-enhanced Magnetic resonance imaging (MRI) and histologic confirmation by one of the following within 6 weeks prior to registration:
  • A positive cerebral spinal fluid (CSF) cytology for lymphoma or a monoclonal lymphocyte population as defined by cell surface markers
  • A biopsy of the vitreous or uvea demonstrating non-Hodgkin's lymphoma
  • Brain biopsy

Note: Patients in whom the type of lymphoma could not be determined or is unknown (eg, not enough tissue for further analysis) are assumed to have a B cell lymphoma and are eligible.

  • The patient must agree to submit tissue (i.e., the original H/E stained slides and immunohistochemistry studies) for central pathology review post-registration.
  • No evidence of systemic non-Hodgkin lymphoma as demonstrated by a computed tomography (CT) scan of the chest, abdomen and pelvis within 6 weeks prior to registration (Note: Bone marrow biopsy is not required for registration but must be obtained prior to start of treatment.)
  • Age ≥ 18
  • History and physical examination within 6 weeks of registration
  • Karnofsky performance status (KPS) equal to 50 or higher, with the following exception
  • Patients with KPS 30 to 50 are eligible if the reason for the poor performance status is neurologic deficit from primary central nervous system (CNS) lymphoma. (Patients with KPS 30 to 50 due to reasons other than primary CNS lymphoma are ineligible. Patients with KPS under 30 for any reason are ineligible)
  • Patient must have documentation of negative HIV-1 testing within 6 weeks prior to study registration (Separate counseling and consent as per institutional guidelines)
  • Complete blood count (CBC)/differential obtained within 2 weeks prior to study registration, with adequate bone marrow function defined as follows:
  • Absolute neutrophil count (ANC) ≥ 1, 500 cells/mm3;
  • Platelets ≥ 100,000 cells/mm3;
  • Hemoglobin (Hgb) ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.);
  • Adequate liver function within 2 weeks prior to study registration, defined as follows:
  • Bilirubin 50cc/min/1.73m2, using the Cockcroft-Gault equation, as follows:

Male: CrCl (ml/min) = (140-age) X (Actual weight in kg) / 72 x serum Creatinine (mg/dl).

Female: CrCl (ml/min) = (140-age) X (Actual weight in kg) X 0.85 / 72 x serum Creatinine (mg/dl).

Note: A measured CrCl from a 24 hour urine collection may also be used.

  • Women of childbearing potential and male participants must agree to practice adequate contraception during therapy
  • Patient must provide study-specific informed consent prior to study registration
  • Patient must be able to swallow pills.

Exclusion Criteria

  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
  • Prior treatment with chemotherapy or radiotherapy for lymphoma or chronic lymphocytic leukemia; note that prior chemotherapy for a different cancer is allowable; see section 1
  • Prior cranial irradiation
  • Severe, active co-morbidity, defined as follows:
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
  • Transmural myocardial infarction within the last 6 months;
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
  • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol.
  • Known pre-existing immunodeficiency as seen in organ transplant recipient.
  • Pre
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01399372). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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