Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Erlotinib Hydrochloride

Gefitinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

This protocol is a phase 1, single arm, open label study of combination daily low dose erlotinib plus twice weekly high dose erlotinib in patients with EGFR-Mutant lung cancer who have not yet received erlotinib or gefitinib. Six dose levels are planned for escalation, with the pulse dose erlotinib increasing.

Expansion cohort A: Treat an additional 19 pts at the MTD with CNS involvement at diagnosis

Cycle 1, week 1 (D1-D7) will consist of pulse dose erlotinib on D1 \& D2 without daily low dose erlotinib on D3-7. For all subsequent weeks, patients will take high dose erlotinib on D1 \& D2, \& will receive erlotinib 50 mg oral daily x 5 days on days 3-7. On days 1 \& 2, patients will take one of the following doses of erlotinib, depending on the dose cohort they are enrolled in: Dose level 1 600 mg oral daily on D1, D2 Dose level 2 750 mg oral daily on D1, D2 Dose level 3 900 mg oral daily on D1, D2 Dose level 4 1050 mg oral daily on D1, D2. An additional Dose -1 (pulse dose erlotinib on D1, D2 with 25 mg oral daily x 5 days in D3-D7) will be reserved, in the unlikely situation that Dose 1 is proved too toxic. If Dose -1 is tolerated well (600mg oral daily D1, D2 \& 25mg oral daily D3-D7), pulse dose escalation can continue as described above, with erlotinib at the daily low dose of 25 mg oral on D3-D7.

erlotinib

Helena Yu, MD

The purpose of this study is to test the safety of different ways of taking erlotinib. The investigators want to find out what effects, good and/or bad, combination daily low dose and twice weekly high dose erlotinib has on the patient and lung cancer. The investigators are also seeing whether different schedules of erlotinib are better at treating lung cancer that has spread to the central nervous system.

CNS expansion phase:

The pulse continuous regimen will be then assess in patients with EGFR mutant lung cancers and CNS involvement. An additional expansion cohort (A) will enroll 19 patients with newly diagnosed EGFR mutant lung cancer with CNS involvement at diagnosis. The patients in the expansion cohorts will undergo the same treatment plan as the patients in the dose expansion cohort. A patient in the expansion cohorts will not be replaced if he/she does not finish the first 28 day (cycle 1) treatment period.

Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer

A Phase 1 Trial of Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer

The study will use a standard 3+3 dose escalation design. Three to six patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.

Toxicity will be graded according to NCI CTCAE, version 4.0. The analysis of safety/tolerability data will be descriptive; toxicity events will be individually tabulated.

Progression free survival (PFS) is defined as the duration of time from first treatment to time of progression or death, whichever occurs first.

sum of complete responses and partial responses according to RECIST 1.1

Overall survival (OS) is defined as the duration of time from first treatment to time of death.

Astellas Pharma US, Inc.

Memorial Sloan Kettering Cancer Center

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lymphoma

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Primary Central Nervous System Lymphoma

Antirheumatic Agents

Cyclophosphamide

Rituximab

Busulfan

Thiotepa

Autologous stem cell transplant following high-dose chemotherapy

Autologous stem cell transplant

High-dose chemotherapy with rituximab, thiotepa, busulfan, and cyclosphosphamide

High-dose chemotherapy

Yi-Bin A Chen, MD

Current standard treatments for lymphoma involving the central nervous system include chemotherapy or whole brain radiation therapy (WBRT). However, many patients do not respond to this treatment, and some of the patients who do respond relapse after treatment.

Previous research has shown that a stem cell transplant of a patient's own cells (autologous stem cell transplant) may be more effective for some patients with lymphoma involving the CNS. In previous research using autologous stem cell transplants for lymphoma involving the CNS, a conditioning regimen consisting of the drugs thiotepa, busulfan and cyclophosphamide (TCE) was used. These drugs have been shown to enter the nervous system.

In this research study, the investigators are adding the drug rituximab (Rituxan) to the drug cytarabine for the stem cell mobilization process. Cytarabine is a standard drug for mobilization. In addition, rituximab will be added to the conditioning regimen of thiotepa, busulfan and cyclophosphamide. Rituximab is approved by the FDA for the treatment of some types of lymphomas, but is not approved for use in lymphomas that involve the CNS. Rituximab is known to be able to enter the CNS. Previous research has suggested that it may help treat lymphoma that involves the CNS.

The goal of this research study is to see if adding rituximab to the stem cell mobilization and conditioning regimens helps treat lymphoma that involves the central nervous system.

If the screening procedures confirm that you are eligible to participate in the research study you will have the following procedures.

Stem cell mobilization - this will take place over at least 9 days to prepare you to donate your stem cells for your autologous transplant. The drugs cytarabine, rituximab and Neupogen (G-CSF) will be given. You will be in the hospital for 2 days to receive the cytarabine infusions (and the 1st rituximab infusion of day 1 of stem cell mobilization). Then you will be discharged. You will receive the Neupogen injections as an outpatient.

Stem cell collection (leukapheresis) - When your doctor determines that your stem cell count is high enough you will have your stem cells collected by a procedure called leukapheresis. Leukapheresis is performed by collecting blood from a vein and processing it through a machine that removes the stem cells that are needed to produce bone marrow. The rest of the blood is returned to you through another vein. The harvested stem cells will be frozen and stored. These cells will be returned to you after you complete the conditioning regimen with high dose chemotherapy.

Conditioning regimen (high dose chemotherapy) - You will enter the hospital for the conditioning regimen and stay for about 30 days after you receive your stem cell transplant. The conditioning regimen to help kill cancer cells before your stem cell transplant will take place over 9 days. All drugs will be given intravenous (through an IV).

Infusion of stem cells (stem cell transplant) - Your cells will be given to you through your vein, similar to an IV infusion. The infusion usually takes several hours.

After you are discharged, you will be asked to return at about 4 weeks, 8 weeks, 12 weeks and 14 weeks after the stem cell transplant. At each visit you will have a physical exam, questions to measure your mental functioning, blood tests. About 14 weeks after the stem cell transplant you will have an eye exam, echocardiogram, lung function tests, whole body PET-CT scan, brain MRI or CT scan, MRI or CT of spinal cord (for patients who may have lymphoma in the spinal cord), collection of cerebral spinal fluid, and bone marrow aspiration.

You will have follow-up visits for 6 month to up to 4 years after the stem cell transplant.

High Dose Chemotherapy and Stem Cell Transplant for Non-Hodgkin's Lymphoma or Central Nervous System (CNS) Lymphoma

Phase II Trial of Hihg-Dose Thiotepa, Busulfan, Cyclophosphamide, and Rituximab With Autologous Stem Cell Transplantation for Patients With CNS Involvement by Non-Hodgkin's Lymphoma or Primary CNS Lymphoma

The proportion of patients with central nervous system (CNS) involvement by B-cell Non-Hodgkin's Lymphoma (NHL), relapsed primary central nervous system lymphoma (PCNSL), or relapsed primary intraocular lymphoma (PIOL) who are alive and progression-free at one year. Relapse was defined as per standard PCNSL criteria from clinical and MRI criteria.

The percentage of participants alive and without disease progression at 2 years. Disease progression was judged through clinical impression and MRI imaging.

The percentage of participants alive after two years

The number of participants that achieved complete remission following high dose chemotherapy and autologous stem cell transplantation (ASCT). Complete remission is defined as the disappearance of all evidence of disease. Response was judged by MRI assessment.

Genentech, Inc.

Otsuka America Pharmaceutical

Dana-Farber Cancer Institute

Massachusetts General Hospital

Principal Investigator

All grade 3 or greater adverse events were considered to be serious adverse events regardless of whether or not the adverse event was believed to be treatment related.

Autologous stem cell transplant: Autologous stem cell transplant following high-dose chemotherapy

High-dose chemotherapy: High-dose chemotherapy with rituximab, thiotepa, busulfan, and cyclosphosphamide

High-dose Chemotherapy With Autologous Stem Cell Transplant

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United States

Region of Enrollment

Diffuse Large B-cell Lymphoma

CLL/ SLL

Follicular Non-Hodgkin lymphoma

CLL: Chronic lymphocytic leukemia SLL: Small lymphocytic lymphoma

Histology

High-Dose Intravenous Methotrexate

High-Dose Cytarabine

Rituximab (Intravenous)

Whole brain radiation therapy (WBRT)

Other Radiation Therapy

Prior Treatment History

Dr. Yi-Bin Chen

The participant that was lost to follow-up was not available for analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer	NCT01967095	EGFR-Mutant Lun...	erlotinib	18 Years -	Memorial Sloan Kettering Cancer Center
Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer	NCT01967095	EGFR-Mutant Lun...	erlotinib	18 Years -	Memorial Sloan Kettering Cancer Center
High Dose Chemotherapy and Stem Cell Transplant for Non-Hodgkin's Lymphoma or Central Nervous System (CNS) Lymphoma	NCT01182415	Non-Hodgkin's L... CNS Lymphoma	Autologous stem... High-dose chemo...	18 Years - 75 Years	Massachusetts General Hospital

Spots Global Cancer Trial Database for cns involvement