Pilot Study of MGd + High-dose MTX-Based Chemoimmunotherapy + RT for Newly Dx PCNSL

NCT00734773 | Withdrawn Early Phase 1 DMC

• 2 other identifiers: NU 05H7STU00002443
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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. Radiation therapy uses high-energy x-rays to kill cancer cells. Motexafin gadolinium may make cancer cells more sensitive to radiation therapy and combination chemotherapy. Giving motexafin gadolinium together with chemotherapy, rituximab, and radiation therapy may kill more cancer cells. PURPOSE: This phase II trial is studying the side effects of giving motexafin gadolinium together with combination chemotherapy, rituximab, and whole-brain radiation therapy and to see how well it works in treating patients with newly diagnosed primary central nervous system lymphoma.

Conditions

Brain and Central Nervous System Tumors; Lymphoma; Neurotoxicity

Keywords

neurotoxicity; primary central nervous system non-Hodgkin lymphoma; primary central nervous system Hodgkin lymphoma

Outcome Measures

Primary Outcomes (3)

• Toxicity of motexafin gadolinium (MGd) and rituximab added to high-dose methotrexate, procarbazine hydrochloride, and vincristine (MPV) chemotherapy

  To evaluate toxicity of motexafin gadolinium (MGd) and rituximab to high-dose methotrexate, procarbazine hydrochloride, and vincristine (MPV) chemotherapy at Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.

  Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.

• Toxicity of MGd added to whole-brain radiotherapy (WBRT)

  To evaluate the toxicity of MGd added to whole-brain radiotherapy (WBRT).

  Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.

• Tumor-selective uptake of MGd

  To evaluate Tumor-selective uptake of MGd

  Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.

Secondary Outcomes (6)

• Overall response rate (complete remission [CR] and partial remission [CR]) to pre-radiation chemo-immunotherapy (R-MPV with MGd)

  Every 3 months for the first year after completed treatment, every 4 months for the second year, every 6 months until the 5th year and then annually.

• Complete response rate to pre-radiation chemo-immunotherapy (R-MPV with MGd)

  Every 3 months after completion of treatment, exams every 3 months for the first year then every 4 - 6 months thereafter.

• Overall survival at 1 year

  Every 3 months for the first year after completed treatment, every 4 months for the second year, every 6 months until the 5th year and then annually.

• Event-free survival at 1 year

  Every 3 months for the first year after completed treatment, every 4 months for the second year, every 6 months until the 5th year and then annually.

• Progression-free survival at 1 year

  Every 3 months for the first year after completed treatment, every 4 months for the second year, every 6 months until the 5th year and then annually.

Interventions

Rituximab BIOLOGICAL

Infusion will be given at week 2, week 4, week 6 and week 8. Infusions can be administered at an initial rate of 100 mg/hr, and increased by 100 mg/hr increments at 30-minute intervals, to a maximum of 400 mg/hr as tolerated.

Also known as: Rituxan

Cytarabine DRUG

Administered by IV over 3 hours at a dose of 3 g/m2/day for 2 days given at week 17 and week 21.

Also known as: Cytosar-U, Ara-c

Methotrexate DRUG

Administered by IV at dose of 3.5 grams/m2 on day 1 of week 1, week 3, week 5, week 7 and week 9; if CSF was positive it will also be given intrathecally on day 8 of week 1, week 3, week 5, week 7 and week 9.

Also known as: MTX, Rheumatrex, Trexall

Motexafin gadolinium DRUG

* Administered to the first five patients enrolled on trial, MGd will be given at 5 mg/kg q day x2 doses (completed on 2 consecutive days 1 to 2 weeks prior to day of cycle 1) to be followed by a non-infused MRI (without contrast) 1-5 hours after 2nd MGd dose (to evaluate for MGd tumor selective uptake). * For induction chemotherapy, MGd 10 mg/kg will be given intravenously on day 8 of each cycle. MGd will be given immediately after Rituxan. * During radiation therapy, MGd will be administered at 5 mg/kg 2-5 hours prior to WBRT, daily for the first 10 days (fractions) and then every other day of radiation thereafter.

Also known as: MGd

Procarbazine hydrochloride DRUG

Taken orally, 100 mg/m2 days 1-7 of the 1st, 3rd, and 5th cycles of induction therapy.

Also known as: Matulane

Vincristine sulfate DRUG

Administered by IV at a dose of 1.4mg per meter squared on weeks 1, 3, 5, 7 and 9.

Also known as: Vincasar PFS

Radiation therapy RADIATION

Given at weeks 11 through 16.

Also known as: Whole Brain Radiation Therapy (WBRT)

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed primary CNS lymphoma (PCNSL) diagnosed by brain biopsy, CSF cytology, or vitreal biopsy * Newly diagnosed disease * Patients who have an inconclusive biopsy or who are not candidates for biopsy may be eligible provided they have a typical cranial MRI or CT scan (defined as the presence of hypo-, iso- or hyperdense parenchymal contrast-enhancing, usually homogeneously) mass lesion(s) and meet at least one of the following criteria: * Positive cerebrospinal fluid cytology for lymphoma or a monoclonal lymphocyte population as defined by cell surface markers * Biopsy of the vitreous or uvea demonstrating non-Hodgkin lymphoma * Measurable (defined as reproducibly measurable disease in two perpendicular dimensions on radiologic study) or evaluable disease PATIENT CHARACTERISTICS: * ECOG performance status 0-3 * Life expectancy ≥ 8 weeks * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Bilirubin ≤ 2.0 mg * SGOT ≤ 2 times upper limit of normal * Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance \> 50 cc/min * Not pregnant or nursing * Fertile patients must use effective contraception during and for 6 months after completion of study therapy * HIV negative * No other active primary malignancy with the exception of basal cell carcinoma of the skin or cervical carcinoma in situ PRIOR CONCURRENT THERAPY: * No prior cranial irradiation * No prior chemotherapy for CNS lymphoma

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

Sponsors & Collaborators

• Northwestern University: lead
• Pharmacyclics LLC.: collaborator

MeSH Terms

Conditions

Central Nervous System Neoplasms; Lymphoma; Neurotoxicity Syndromes

Interventions

Rituximab; Cytarabine; Methotrexate; motexafin gadolinium; Procarbazine; Vincristine; Radiotherapy

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Poisoning; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Therapeutics

Study Officials

• Andrew M. Evens, DO, MS

  Robert H. Lurie Cancer Center

  PRINCIPAL INVESTIGATOR

• Jeffrey J. Raizer, MD

  Robert H. Lurie Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 13, 2008
• First Posted: August 14, 2008
• Study Start: November 1, 2008
• Last Updated: May 18, 2012

Record last verified: 2012-05