RTOG 0227 - "Phase I/II Study of Pre-Irradiation Chemotherapy With Methotrexate, Rituximab, and Temozolomide and Post-Irradiation Temozolomide for Primary Central Nervous System Lymphoma"

Treatment Plan    (Supplied Drug:  Temozolomide)

Pre-RT Chemo

Rituximab:  375mg/m², IV, 3 days prior to 1st cycle of MTX

Methotrexate (MTX):  3.5gm/m², IV over 4 hrs, with Leucovorin rescue, Wks 1, 3, 5, 7, 9 (total 5 cycles)

Temozolomide (TMZ):  PO, QD x 5 days, Wks 4 & 8 using following Phase I & II schedules:

Phase I (See protocol for details)

Arm 1:  100mg/m², daily

Arm 2:  150mg/m², daily

Arm 3:  200mg/m², daily

Phase II

Arm 4:  MTD from Phase I (100mg/m², daily)

RT

Whole Brain RT:  1.2Gy, BID fxs, 5 days/wk, Wks 11, 12, 13 (total 36Gy)

Post-RT Chemo

TMZ:  200mg/m², PO, QD x 5 days, Wks 14, 18, 22, 26, 30, 34, 38, 42, 46 & 50 (total 10 cycles)

Eligibility

• Prim CNS lymphoma (B-cell, CD20 positive) based on positive bx or CSF or vitreous cytology (in association w/meas intraparenchymal tumor).  Cytology must demonstrate lymphoma or have immunohistochemical dx of malignant lymphocytes w/monoclonal lymphocytic population.

• Life expectancy >8 wks.

• Zubrod 0-2.

• AGC >1500/mm³; platelets >100,000/mm³; CrCl >50 (using Cockcroft-Gault formula); bili, SGOT, & alk phos <2x IULN.

• No systemic lymphoma.

• No prior malignancy (except in situ cervical carcinoma or non-melanoma skin cancer) unless disease-free >5 yrs.

• No prior RT to brain or head/neck.

• No prior chemo.

• No hx of idiopathic sensitivity to any of drugs to be used.

• No active infectious process.

• No seropositive pts for HIV, AIDS, or post-organ transplant.

• No pregnant women.

• No active Hepatitis B.

• PRESTUDY REQUIREMENTS

  • H&P (including hx of present illness, review of systems, past medical hx, family hx, meds, complete physical & neuro exams, Zubrod, ht/wt, BSA)*

  • CBC, diff, platelets*

  • Lytes, LFTs, BUN/creat*

  • CrCl (Cockcroft-Gault or by 24-hr urine collection)*

  • β-hCG (women of childbearing potential; urine hCG is acceptable)*

  • PFTs (if known pulmonary or bronchospastic disease)**

  • MRI brain (or head CT) - pre-op MRI is sufficient if there has been no tumor debulking**

  • Slit-lamp exam**

  • CSF for cytology**

  • Hepatitis B screening**

  • MMSE*

  • Spitzer QOL Asmt*

  *      Within 1 wk prior to 1st tx cycle

  **    Within 4 wks prior to 1st tx cycle

• Signed informed consent.