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

NCT00248534 | Terminated Phase 2 Results DMC

• 5 other identifiers: NABTC05-01NABTC-05-01CDR0000445289NCI-2012-02673U01CA062399
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 7

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.

Conditions

Lymphoma

Keywords

primary central nervous system non-Hodgkin lymphoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Objective Response

  Objective response rate of the combination of Rituximab and TMZ

  2 months

Secondary Outcomes (3)

• Number of Participants Alive at 3 Years

  3 years

• 1 Year Overall Survival Rate

  1 year

• 6-month Progression-free Survival

  6 months

Study Arms (1)

IV Rituximab

EXPERIMENTAL

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; Drug: methylprednisolone; Drug: temozolomide

Interventions

rituximab BIOLOGICAL

given IV days 1,8, 15 and 22

IV Rituximab

methylprednisolone DRUG

2hr IV every 28 days post consolidation cycles of Temozolomide (TMZ) (6 cycles TMZ = Consolidation cycles)

IV Rituximab

temozolomide DRUG

Induction Days 1-7 and 15-21 (150mg/m2 PO) Consolidation days 1-5 every 28 days X 6 cycles

Also known as: TMZ

IV Rituximab

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

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

Study Sites (7)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Hillman Cancer Center at University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78284-6220, United States

Location

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

Related Publications (2)

• Nayak L, Abrey LE, Drappatz J, et al.: Multicenter phase II trial of temozolomide (TMZ) and rituximab (RIT) for recurrent primary CNS lymphoma (PCNSL): North American Brain Tumor Consortium (NABTC) study 05-01. [Abstract] J Clin Oncol 29 (Suppl 15): A-2039, 2011.

  RESULT

• Nayak L, Abrey LE, Drappatz J, Gilbert MR, Reardon DA, Wen PY, Prados M, Deangelis LM, Omuro A; North American Brain Tumor Consortium. Multicenter phase II study of rituximab and temozolomide in recurrent primary central nervous system lymphoma. Leuk Lymphoma. 2013 Jan;54(1):58-61. doi: 10.3109/10428194.2012.698736. Epub 2012 Jul 9.

  PMID: 22656234 DERIVED

MeSH Terms

Conditions

Lymphoma

Interventions

Rituximab; Methylprednisolone; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

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

Results Point of Contact

• Title: Lauren Abrey, MD
• Organization: North American Brain Tumor Consortium

jfisher@jhmi.edu

410-955-3657

Study Officials

• Lauren E. Abrey, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2005
• First Posted: November 4, 2005
• Study Start: September 1, 2005
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: September 4, 2018
• Results First Posted: September 4, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)