Rituximab, Temozolomide, and Methylprednisolone in Treating Patients With Recurrent Primary CNS Non-Hodgkin's Lymphoma

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00248534
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 16
• Locations: 7
• Arm: 1
• Duration (Months): 84
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as temozolomide and methylprednisolone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Rituximab may help chemotherapy kill more cancer cells by making cancer cells more sensitive to the drugs. Giving rituximab together with temozolomide and methylprednisolone may be an effective treatment for primary CNS non-Hodgkin's lymphoma.

PURPOSE: This phase II trial is studying how well giving rituximab together with temozolomide and methylprednisolone works in treating patients with recurrent primary CNS non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab; Drug: methylprednisolone; Drug: temozolomide	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the response rate in patients with recurrent primary CNS non-Hodgkin's lymphoma treated with rituximab, temozolomide, and methylprednisolone.

Secondary

• Determine the overall and 6-month progression-free survival of patients treated with this regimen.

OUTLINE: Induction therapy: Patients receive rituximab IV over 30-60 minutes on days 1, 8, 15, and 22 and oral temozolomide daily on days 1-7 and 15-21. After day 28, patients with stable disease or better proceed to consolidation therapy.

Consolidation therapy: Patients receive oral temozolomide daily on days 1-5. Treatment repeats every 28 days for up to 6 courses. Patients achieving a complete remission proceed to maintenance therapy.

Maintenance therapy: Patients receive methylprednisolone IV over 2 hours on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within approximately 13.3 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Rituximab and Temozolomide in Recurrent Primary CNS Lymphoma
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IV Rituximab IV Rituximab 750mg/m2 single infusion every week for up to 4 weeks. Induction: Rituximab (750mg/m2) Day 1, 8, 15 and 22 and Temozolomide [TMZ] (150mg/m2) days 1-7 and 15-21, followed by six cycles of consolidation TMZ 150-200mg/m2 x5/28days, followed by maintenance with methylprednisolone (1g IV every 28days) until progression	Biological: rituximab; given IV days 1,8, 15 and 22; Drug: methylprednisolone; 2hr IV every 28 days post consolidation cycles of Temozolomide (TMZ) (6 cycles TMZ = Consolidation cycles); Drug: temozolomide; Induction Days 1-7 and 15-21 (150mg/m2 PO) Consolidation days 1-5 every 28 days X 6 cycles; Other Names: TMZ

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Objective Response [2 months]

   Objective response rate of the combination of Rituximab and TMZ

Secondary Outcome Measures

1. Number of Participants Alive at 3 Years [3 years]

   The intent was to measure Median Overall Survival at 3 years, however only one participant was analyzable at this time point. Therefore, the number of participants who survived is reported instead.

2. 1 Year Overall Survival Rate [1 year]

3. 6-month Progression-free Survival [6 months]

   Scan at 6 months Complete response: Complete disappearance of all tumor on MRI scan, off all glucocorticoids with stable or improving neurological exam minimum of 4 wks Partial response: Greater than or equal 50% reduction in tumor size on MRI, on sable or decreasing glucocorticoids with stable or improving neurological exam for a minimum of 4 wks. Progressive disease: Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion. Stable disease: Clinical status and MRI does not qualify for complete response, partial response or progression

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed primary CNS non-Hodgkin's lymphoma by brain biopsy, positive cerebrospinal fluid cytology, or vitrectomy

• Recurrent disease

• Measurable disease, define as bi-dimensionally measurable lesions with clearly defined margins by brain MRI or CT scan

• Radiographical evidence of tumor progression by MRI or CT scan

• Steroid therapy must be stable for 5 days prior to scan

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• More than 8 weeks

Hematopoietic

• WBC ≥ 3,000/mm^3

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 10 g/dL (transfusion allowed)

Hepatic

• SGOT < 2 times upper limit of normal (ULN)

• Bilirubin < 2 times ULN

• No active or latent hepatitis B infection

Renal

• Creatinine < 1.5 mg/dL OR

• Creatinine clearance ≥ 60 mL/min

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

• No uncontrolled significant medical illness that would preclude study treatment

• No active infection

• No active HIV infection

• No concurrent disease that would dangerously alter drug metabolism or obscure toxicity

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 7 days since prior interferon or thalidomide

• No concurrent prophylactic filgrastim (G-CSF)

• No concurrent immunotherapy

Chemotherapy

• No prior temozolomide

• At least 14 days since prior methotrexate

• At least 21 days since prior procarbazine

• At least 42 days since prior nitrosoureas

• No other concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics

• At least 7 days since prior tamoxifen

• No concurrent hormonal therapy

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• Recovered from all prior therapy

• At least 28 days since prior investigational agents

• At least 28 days since other prior cytotoxic therapy

• At least 7 days since other prior non-cytotoxic agents (e.g., tretinoin) (radiosenitizers allowed)

• No other concurrent investigational drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
2	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
3	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
4	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
5	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
6	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-6220
7	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• National Cancer Institute (NCI)

Investigators

• Study Chair: Lauren E. Abrey, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00248534
• Other Study ID Numbers: NABTC05-01; NABTC-05-01; CDR0000445289; NCI-2012-02673; U01CA062399
• First Posted: Nov 4, 2005
• Last Update Posted: Sep 4, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: primary central nervous system non-Hodgkin lymphoma
• Additional relevant MeSH terms: Lymphoma; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Rituximab; Temozolomide; Prednisolone hemisuccinate; Prednisolone phosphate

Study Results

Participant Flow

Recruitment Details	patients enrolled from 2005 through 2008. Patients enrolled in an outpatient multi-institutional clinics

Arm/Group Title	IV Rituximab
Arm/Group Description	IV Rituximab 750mg/m2 single infusion every week for up to 4 weeks. Induction: Rituximab (750mg/m2) Day 1, 8, 15 and 22 and Temozolomide [TMZ] (150mg/m2) days 1-7 and 15-21, followed by six cycles of consolidation TMZ 150-200mg/m2 x5/28days, followed by maintenance with methylprednisolone (1g IV every 28days) until progression rituximab: given IV days 1,8, 15 and 22 methylprednisolone: 2hr IV every 28 days post consolidation cycles of Temozolomide (TMZ) (6 cycles TMZ = Consolidation cycles) temozolomide: Induction Days 1-7 and 15-21 (150mg/m2 PO) Consolidation days 1-5 every 28 days X 6 cycles
Period Title: Overall Study
STARTED	16
COMPLETED	16
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	IV Rituximab
Arm/Group Description	IV Rituximab 750mg/m2 single infusion every week for up to 4 weeks. Induction: Rituximab (750mg/m2) Day 1, 8, 15 and 22 and Temozolomide [TMZ] (150mg/m2) days 1-7 and 15-21, followed by six cycles of consolidation TMZ 150-200mg/m2 x5/28days, followed by maintenance with methylprednisolone (1g IV every 28days) until progression rituximab: given IV days 1,8, 15 and 22 methylprednisolone: 2hr IV every 28 days post consolidation cycles of Temozolomide (TMZ) (6 cycles TMZ = Consolidation cycles) temozolomide: Induction Days 1-7 and 15-21 (150mg/m2 PO) Consolidation days 1-5 every 28 days X 6 cycles
Overall Participants	16
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	63
Sex: Female, Male (Count of Participants)
Female	12 75%
Male	4 25%
Karnofsky Performance Status Scale (units on a scale) [Median (Full Range) ]
Median (Full Range) [units on a scale]	90

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Objective Response
Description	Objective response rate of the combination of Rituximab and TMZ
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

2 patients were not evaluable, one died prematurely and the other withdrew consent before the first scan (during induction cycle)

Arm/Group Title	IV Rituximab
Arm/Group Description	IV Rituximab 750mg/m2 single infusion every week for up to 4 weeks. Induction: Rituximab (750mg/m2) Day 1, 8, 15 and 22 and Temozolomide [TMZ] (150mg/m2) days 1-7 and 15-21, followed by six cycles of consolidation TMZ 150-200mg/m2 x5/28days, followed by maintenance with methylprednisolone (1g IV every 28days) until progression rituximab: given IV days 1,8, 15 and 22 methylprednisolone: 2hr IV every 28 days post consolidation cycles of Temozolomide (TMZ) (6 cycles TMZ = Consolidation cycles) temozolomide: Induction Days 1-7 and 15-21 (150mg/m2 PO) Consolidation days 1-5 every 28 days X 6 cycles
Measure Participants	14
Number (95% Confidence Interval) [percent of participants]	14 87.5%

2. Secondary Outcome

Title	Number of Participants Alive at 3 Years
Description	The intent was to measure Median Overall Survival at 3 years, however only one participant was analyzable at this time point. Therefore, the number of participants who survived is reported instead.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

One patient died prematurely, one patient withdrew consent before first scan (during induction), 13 patients came off study due to progression of disease.

Arm/Group Title	IV Rituximab
Arm/Group Description	IV Rituximab 750mg/m2 single infusion every week for up to 4 weeks. Induction: Rituximab (750mg/m2) Day 1, 8, 15 and 22 and Temozolomide [TMZ] (150mg/m2) days 1-7 and 15-21, followed by six cycles of consolidation TMZ 150-200mg/m2 x5/28days, followed by maintenance with methylprednisolone (1g IV every 28days) until progression rituximab: given IV days 1,8, 15 and 22 methylprednisolone: 2hr IV every 28 days post consolidation cycles of Temozolomide (TMZ) (6 cycles TMZ = Consolidation cycles) temozolomide: Induction Days 1-7 and 15-21 (150mg/m2 PO) Consolidation days 1-5 every 28 days X 6 cycles
Measure Participants	1
Count of Participants [Participants]	1 6.3%

3. Secondary Outcome

Title	1 Year Overall Survival Rate
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Rituximab
Arm/Group Description	IV Rituximab 750mg/m2 single infusion every week for up to 4 weeks. Induction: Rituximab (750mg/m2) Day 1, 8, 15 and 22 and Temozolomide [TMZ] (150mg/m2) days 1-7 and 15-21, followed by six cycles of consolidation TMZ 150-200mg/m2 x5/28days, followed by maintenance with methylprednisolone (1g IV every 28days) until progression rituximab: given IV days 1,8, 15 and 22 methylprednisolone: 2hr IV every 28 days post consolidation cycles of Temozolomide (TMZ) (6 cycles TMZ = Consolidation cycles) temozolomide: Induction Days 1-7 and 15-21 (150mg/m2 PO) Consolidation days 1-5 every 28 days X 6 cycles
Measure Participants	16
Number (95% Confidence Interval) [percentage of participants]	71 443.8%

4. Secondary Outcome

Title	6-month Progression-free Survival
Description	Scan at 6 months Complete response: Complete disappearance of all tumor on MRI scan, off all glucocorticoids with stable or improving neurological exam minimum of 4 wks Partial response: Greater than or equal 50% reduction in tumor size on MRI, on sable or decreasing glucocorticoids with stable or improving neurological exam for a minimum of 4 wks. Progressive disease: Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion. Stable disease: Clinical status and MRI does not qualify for complete response, partial response or progression
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Rituximab
Arm/Group Description	IV Rituximab 750mg/m2 single infusion every week for up to 4 weeks. Induction: Rituximab (750mg/m2) Day 1, 8, 15 and 22 and Temozolomide [TMZ] (150mg/m2) days 1-7 and 15-21, followed by six cycles of consolidation TMZ 150-200mg/m2 x5/28days, followed by maintenance with methylprednisolone (1g IV every 28days) until progression rituximab: given IV days 1,8, 15 and 22 methylprednisolone: 2hr IV every 28 days post consolidation cycles of Temozolomide (TMZ) (6 cycles TMZ = Consolidation cycles) temozolomide: Induction Days 1-7 and 15-21 (150mg/m2 PO) Consolidation days 1-5 every 28 days X 6 cycles
Measure Participants	16
Number (95% Confidence Interval) [percentage of participants]	13 81.3%

Adverse Events

Time Frame	3 years
Arm/Group Title	IV Rituximab
Arm/Group Description	IV Rituximab 750mg/m2 single infusion every week for up to 4 weeks. Induction: Rituximab (750mg/m2) Day 1, 8, 15 and 22 and Temozolomide [TMZ] (150mg/m2) days 1-7 and 15-21, followed by six cycles of consolidation TMZ 150-200mg/m2 x5/28days, followed by maintenance with methylprednisolone (1g IV every 28days) until progression rituximab: given IV days 1,8, 15 and 22 methylprednisolone: 2hr IV every 28 days post consolidation cycles of Temozolomide (TMZ) (6 cycles TMZ = Consolidation cycles) temozolomide: Induction Days 1-7 and 15-21 (150mg/m2 PO) Consolidation days 1-5 every 28 days X 6 cycles
All Cause Mortality
	IV Rituximab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	IV Rituximab
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Other (Not Including Serious) Adverse Events
	IV Rituximab
	Affected / at Risk (%)	# Events
Total	14/16 (87.5%)
Blood and lymphatic system disorders
hematotoxicity	8/16 (50%)	8
General disorders
fatigue	3/16 (18.8%)	3
Investigations
liver enzyme elevation	2/16 (12.5%)	2
Skin and subcutaneous tissue disorders
skin rash	1/16 (6.3%)	1

Limitations/Caveats

slow accrual, preliminary analysis suggesting futility and combining of consortia, trial closed early

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.