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NCT00068250 · REGISTRY CONDITION SEARCH

Combination Chemotherapy, Monoclonal Antibody, and Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE1, PHASE2
Status at capture
COMPLETED
Registry last update
2018-02-07

RATIONALE: Drugs used in chemotherapy such as methotrexate and temozolomide use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining methotrexate, temozolomide, and rituximab with radiation therapy may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of temozolomide when given together with methotrexate and rituximab followed by radiation therapy and to see how well they work in treating patients with primary central nervous system lymphoma.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Phase I Participants Experiencing Toxicity

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outcome · POSTED

Phase II: Overall Survival Rate at 2 Years (Including Phase I Patients at Same Dose)

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outcome · POSTED

Phase II: Pre-irradiation Chemotherapy Tumor Response Rate (Including Phase I Patients at Same Dose)

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outcome · POSTED

Phase II: Progression-free Survival (Including Phase I Patients at Same Dose)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion criteria: 1. Primary central nervous system (CNS) lymphoma \[B-cell, Cluster of Differentiation 20 (CD20) antigen positive\] based on positive biopsy or cerebrospinal fluid (CSF) or vitreous cytology (in association with measurable intraparenchymal tumor). Cytology must demonstrate lymphoma or have an immunohistochemical diagnosis of malignant lymphocytes with a monoclonal lymphocytic population. 2. Life expectancy ≥ 8 weeks; 3. Zubrod performance status of 0-2; 4. Absolute granulocyte count ≥1500/mm3; platelet count ≥ 100,000/mm3; creatinine clearance ≥ 50, calculated with the Cockcroft-Gault Equation: Cr Clearance = (140-age) x wt (kg)/(Cr\[mg/dl\]x 72); Bilirubin, serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (AST) ≤ 2 x institutional upper limits of normal; 5. Patients must sign a study-specific informed consent prior to study entry. 6. Age ≥ 18 Exclusion criteria: 1. Evidence of systemic lymphoma; 2. Prior malignancy (excluding in situ carcinoma of the cervix or non-melanomatous skin cancer)unless disease free for at least five years; 3. Prior radiotherapy to the brain or head/neck; 4. Prior chemotherapy; 5. History of idiopathic sensitivity to any of the drugs to be used; 6. Active infectious process; 7. Seropositive for HIV, AIDS, or post-organ transplant; 8. Pregnant women are ineligible as treatment involves unforeseeable risks to the participant and to the embryo or fetus. 9. Active hepatitis B.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.
    intervention Names
    1. Drug: rituximab
    2. Drug: methotrexate
    3. Drug: temozolomide 100 mg/m^2
    4. Radiation: radiation therapy
    5. Drug: post-radiation therapy temozolomide
    label
    Phase I: Temozolomide 100 mg
    type
    EXPERIMENTAL
  2. description
    Rituximab, methotrexate, temozolomide 150 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.
    intervention Names
    1. Drug: rituximab
    2. Drug: methotrexate
    3. Drug: temozolomide 150 mg/m^2
    4. Radiation: radiation therapy
    5. Drug: post-radiation therapy temozolomide
    label
    Phase I: Temozolomide 150 mg
    type
    EXPERIMENTAL
  3. description
    Rituximab, methotrexate, temozolomide 200 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.
    intervention Names
    1. Drug: rituximab
    2. Drug: methotrexate
    3. Drug: temozolomide 200 mg/m^2
    4. Radiation: radiation therapy
    5. Drug: post-radiation therapy temozolomide
    label
    Phase I: Temozolomide 200 mg
    type
    EXPERIMENTAL
  4. description
    Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.
    intervention Names
    1. Drug: rituximab
    2. Drug: methotrexate
    3. Drug: temozolomide 100 mg/m^2
    4. Radiation: radiation therapy
    5. Drug: post-radiation therapy temozolomide
    label
    Phase II: Temozolomide 100 mg
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Phase I: Temozolomide 100 mg
    2. Phase I: Temozolomide 150 mg
    3. Phase I: Temozolomide 200 mg
    4. Phase II: Temozolomide 100 mg
    description
    375 mg/m2, intravenously three days prior to the first cycle of methotrexate
    name
    rituximab
    type
    DRUG
  2. arm Group Labels
    1. Phase I: Temozolomide 100 mg
    2. Phase I: Temozolomide 150 mg
    3. Phase I: Temozolomide 200 mg
    4. Phase II: Temozolomide 100 mg
    description
    Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle. Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion. Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.
    name
    methotrexate
    type
    DRUG
  3. arm Group Labels
    1. Phase I: Temozolomide 100 mg
    2. Phase II: Temozolomide 100 mg
    description
    Temozolomide 100 mg/m\^2 by mouth per day for five days on weeks 4 and 8.
    name
    temozolomide 100 mg/m^2
    type
    DRUG
  4. arm Group Labels
    1. Phase I: Temozolomide 150 mg
    description
    Temozolomide 150 mg/m\^2 by mouth per day for five days on weeks 4 and 8.
    name
    temozolomide 150 mg/m^2
    type
    DRUG
  5. arm Group Labels
    1. Phase I: Temozolomide 200 mg
    description
    Temozolomide 200 mg/m\^2 per day by mouth for five days on weeks 4 and 8.
    name
    temozolomide 200 mg/m^2
    type
    DRUG
  6. arm Group Labels
    1. Phase I: Temozolomide 100 mg
    2. Phase I: Temozolomide 150 mg
    3. Phase I: Temozolomide 200 mg
    4. Phase II: Temozolomide 100 mg
    description
    Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends). A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.
    name
    radiation therapy
    other Names
    1. radiotherapy
    type
    RADIATION
  7. arm Group Labels
    1. Phase I: Temozolomide 100 mg
    2. Phase I: Temozolomide 150 mg
    3. Phase I: Temozolomide 200 mg
    4. Phase II: Temozolomide 100 mg
    description
    Temozolomide (TMZ) 200 mg/m\^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.
    name
    post-radiation therapy temozolomide
    type
    DRUG
Study design
allocation
NON_RANDOMIZED
intervention Model
SEQUENTIAL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
60
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    A dose limiting toxicity (DLT) is defined as any grade 3 or 4 non-hematological toxicity (other than grade 3 nausea/vomiting) or any hematological toxicity resulting in the discontinuation of temozolomide. Toxicity evaluation for this dose escalation includes all toxicities occurring prior to the start of radiation therapy. If the patient did not receive radiation therapy, then toxicity evaluation included all toxicities occurring through week 15. Any grade 5 toxicity would result in immediate suspension of accrual.
    measure
    Number of Phase I Participants Experiencing Toxicity
    time Frame
    From start of treatment to 10 weeks if radiation therapy received, to 15 weeks if not.
  2. description
    Survival time is defined as time from registration to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. (Please note that this outcome measure is considered the primary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )
    measure
    Phase II: Overall Survival Rate at 2 Years (Including Phase I Patients at Same Dose)
    time Frame
    Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.
secondary Outcomes
  1. description
    Tumor response was centrally reviewed. Complete response: Disappearance of all enhancing tumor, the patient must be off steroid therapy and neurologically stable or improved; partial response: ≥ 50% decrease in enhancing tumor; progressive disease: ≥ 25% increase in a lesion, progressive or newly emergent meningeal or ocular disease. (Please note that this outcome measure is considered a secondary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )
    measure
    Phase II: Pre-irradiation Chemotherapy Tumor Response Rate (Including Phase I Patients at Same Dose)
    time Frame
    From start of treatment to 10 weeks if RT received, to 15 weeks if not.
  2. description
    Progression is defined as greater than 25% increase in enhancing tumor or the appearance of new lesions in the brain, eye, or the appearance of a new positive cerebrospinal fluid (CSF) cytology. The patient may be neurologically stable or worse and on stable or increasing doses of corticosteroid. Progression-free survival time is defined as time from registration to the date of progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. (Please note that this outcome measure is considered a secondary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )
    measure
    Phase II: Progression-free Survival (Including Phase I Patients at Same Dose)
    time Frame
    Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.
Full study description
brief Summary
RATIONALE: Drugs used in chemotherapy such as methotrexate and temozolomide use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining methotrexate, temozolomide, and rituximab with radiation therapy may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of temozolomide when given together with methotrexate and rituximab followed by radiation therapy and to see how well they work in treating patients with primary central nervous system lymphoma.
detailed Description
OBJECTIVES: * To assess the maximum tolerated dose (MTD) of temozolomide (TMZ) in combination with methotrexate (MTX) and rituximab (RTX) when administered prior to twice daily fractionated whole brain radiation therapy (WBRT) in patients with primary central nervous system lymphoma. * To compare the two-year survival rate in patients receiving pre-irradiation chemotherapy, twice daily fractionated whole brain radiation therapy and post-irradiation temozolomide to the reported two-year survival rate of Radiation Therapy Oncology Group (RTOG) trial 93-10. RTOG 9310 does not fall within ClinicalTrials.gov registration/reporting requirements.) * To compare the pre-irradiation chemotherapy tumor response rates to the reported rate from RTOG 93-10. * To report progression-free survival. * To assess acute and long-term neurologic toxicity, and to collect quality of life data for this patient group. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Source references
references
  1. citation
    Glass J, Won M, Schultz CJ, Brat D, Bartlett NL, Suh JH, Werner-Wasik M, Fisher BJ, Liepman MK, Augspurger M, Bokstein F, Bovi JA, Solhjem MC, Mehta MP. Phase I and II Study of Induction Chemotherapy With Methotrexate, Rituximab, and Temozolomide, Followed By Whole-Brain Radiotherapy and Postirradiation Temozolomide for Primary CNS Lymphoma: NRG Oncology RTOG 0227. J Clin Oncol. 2016 May 10;34(14):1620-5. doi: 10.1200/JCO.2015.64.8634. Epub 2016 Mar 28.
    pmid
    27022122
    type
    RESULT
Source notices and limitations
    Discovery and provenance
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        exact text
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      offset unit
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      query cond
      Primary Central Nervous System Lymphoma
      query disease state id
      ds-primary-central-nervous-system-lymphoma
      source file
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    Preserved source evidence · Not medical advice