Idarubicin Based Combined Modality Therapy in Primary CNS Lymphoma

Sponsor

Trans Tasman Radiation Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00193973

Collaborator

Australasian Leukaemia and Lymphoma Group (Other)

Enrollment

Locations

Arm

145

Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Idarubicin combined with high dose methotrexate and moderate dose radiotherapy will achieve similar survival outcomes but with reduced neurotoxicity compared to regimens using methotrexate with high dose radiotherapy.

Condition or Disease	Intervention/Treatment	Phase
Primary Central Nervous System Lymphoma	Drug: Idarubicin, Methotrexate, Filgrastim, intrathecal Ara-C Radiation: Radiation Therapy	Phase 2

Detailed Description

Combined modality therapy in PCNSL has improved survival outcomes but at the cost of unacceptable rates of neurotoxicity when high dose radiotherapy is used. Idarubicin has activity in systemic lymphomas and crosses the blood brain barrier and may add to the efficacy of methotrexate. By combining these 2 drugs with moderate dose radiotherapy survival outcomes should be optimal but with lower rates of neurotoxicity.

Comparison: TROG has previously performed a phase 2 study using methotrexate with high dose radiotherapy and this will allow comparison of survival and neurotoxicity rates.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Study of Idarubicin Based Combined Modality Therapy in Primary Central Nervous System Lymphoma

Study Start Date :

Jul 1, 2001

Actual Primary Completion Date :

Jul 1, 2008

Actual Study Completion Date :

Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1	Drug: Idarubicin, Methotrexate, Filgrastim, intrathecal Ara-C Idarubicin 15mg/m2 days 1, 22. Filgrastim 5mcg/kg until neutrophil recovery days 2, 23. Methotrexate 1g/m2 days 15, 36 and 50. Radiation: Radiation Therapy Whole brain Irradiation, 30Gy in 20 fractions over 4 weeks Other Names: Radiation, Radiotherapy

Arm

Intervention/Treatment

Active Comparator: 1

Drug: Idarubicin, Methotrexate, Filgrastim, intrathecal Ara-C

Idarubicin 15mg/m2 days 1, 22. Filgrastim 5mcg/kg until neutrophil recovery days 2, 23. Methotrexate 1g/m2 days 15, 36 and 50.

Radiation: Radiation Therapy

Whole brain Irradiation, 30Gy in 20 fractions over 4 weeks

Other Names:

Radiation, Radiotherapy

Outcome Measures

Primary Outcome Measures

To estimate the median and 2 year overall survival. [Estimate of survival at 2 years and at 5 years.]

Secondary Outcome Measures

Assess acute toxicity. [Interim actute toxicity analyses will be performed at accrual points: 5, 10, 15, 20 and 25 patients.]
Assess functional indices of living in patients with PCNSL. [Analysis will be at 5 years.]
To estimate the risk of late neurotoxicity relative to results achieved in TROG 92.01. [Analysis at 3 years.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically proven primary CNS lymphoma.
Absence of disease outside the CNS.
ECOG performance status 0-3
Negative HIV status.
Peripheral blood counts with granulocytes >1.5 x 109L and platelets > 100 x 109L. Serum creatinine <150mmol/L. Serum bilirubin <1.5 times and AST <2 times upper limit of normal.
Age >18 and <=70 years.
Patients must give written informed consent.
Corticosteroids prior to histological diagnosis are allowed.

Exclusion Criteria:

Previous history of malignancy (other than non-melanomatous skin carcinoma, or carcinoma in situ of cervix completely excised).
Patients who are pregnant or lactating.
NYHA (New York State Heart Association classification) cardiac failure grade 3
Macroscopic spinal thecal or spinal cord disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Canberra Hospital	Garran	Australian Capital Territory	Australia	2605
2	Calvary Mater Newcastle	Newcastle	New South Wales	Australia	2298
3	Prince of Wales Hospital	Randwick	New South Wales	Australia	2031
4	Westmead Hospital	Wentworthville	New South Wales	Australia	2145
5	Illawarra Cancer Care Centre	Wollongong	New South Wales	Australia
6	Royal Brisbane Hospital	Herston	Queensland	Australia	4029
7	Mater QRI	South Brisbane	Queensland	Australia	4101
8	Premion - Tugun	Tugun	Queensland	Australia	4224
9	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
10	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
11	Andrew Love Cancer Centre, Geelong Hospital	Geelong	Victoria	Australia	3220
12	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	8006
13	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
14	Auckland Hospital	Auckland		New Zealand	1001
15	Christchurch Hospital	Christchurch		New Zealand	4710