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

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ClinicalTrials.gov Identifier: NCT01182415
Recruitment Status : Completed
First Posted : August 16, 2010
Results First Posted : December 29, 2017
Last Update Posted : December 29, 2017
Sponsor:
Collaborators:
Genentech, Inc.
Otsuka America Pharmaceutical
Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Yi-Bin A. Chen, MD, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE April 30, 2010
First Posted Date  ICMJE August 16, 2010
Results First Submitted Date  ICMJE November 27, 2017
Results First Posted Date  ICMJE December 29, 2017
Last Update Posted Date December 29, 2017
Study Start Date  ICMJE June 2010
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 27, 2017)
Proportion of Patients With CNS Involvement by B-cell NHL, Relapsed PCNSL, or Relapsed PIOL Who Are Alive and Progression-free at One Year [ Time Frame: 3 years ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: August 13, 2010)
Proportion of Patients With CNS Involvement by B-cell NHL, Relapsed PCNSL, or Relapsed PIOL Who Are Alive and Progression-free at One Year [ Time Frame: 3 years ]
Change History Complete list of historical versions of study NCT01182415 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 27, 2017)
  • 2-year Progression Free Survival (PFS) [ Time Frame: 2 years ]
    The percentage of participants alive and without disease progression at 2 years.
  • 2-year Overall Survival (OS) [ Time Frame: 2 years ]
    The percentage of participants alive after two years
  • Response Rate [ Time Frame: 3 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2010)
  • 1-year progression free survival (PFS) [ Time Frame: 3 years ]
  • 1-year Event free Survival (EFS) [ Time Frame: 3 years ]
  • 1-year overall survival (OS) [ Time Frame: 3 years ]
  • Overall response rate [ Time Frame: 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE High Dose Chemotherapy and Stem Cell Transplant for Non-Hodgkin's Lymphoma or Central Nervous System (CNS) Lymphoma
Official Title  ICMJE 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
Brief Summary

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.

Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-Hodgkin's Lymphoma
  • CNS Lymphoma
Intervention  ICMJE
  • Procedure: Autologous stem cell transplant
    Autologous stem cell transplant following high-dose chemotherapy
  • Drug: High-dose chemotherapy
    High-dose chemotherapy with rituximab, thiotepa, busulfan, and cyclosphosphamide
Study Arms  ICMJE Experimental: High-dose chemotherapy with autologous stem cell transplant
Interventions:
  • Procedure: Autologous stem cell transplant
  • Drug: High-dose chemotherapy
Publications * Chen YB, Batchelor T, Li S, Hochberg E, Brezina M, Jones S, Del Rio C, Curtis M, Ballen KK, Barnes J, Chi AS, Dietrich J, Driscoll J, Gertsner ER, Hochberg F, LaCasce AS, McAfee SL, Spitzer TR, Nayak L, Armand P. Phase 2 trial of high-dose rituximab with high-dose cytarabine mobilization therapy and high-dose thiotepa, busulfan, and cyclophosphamide autologous stem cell transplantation in patients with central nervous system involvement by non-Hodgkin lymphoma. Cancer. 2015 Jan 15;121(2):226-33. doi: 10.1002/cncr.29023. Epub 2014 Sep 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 13, 2010)
30
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2016
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • One of the following clinical criteria:secondary CNS NHL; synchronous CNS NHL; relapsed PCNSL; relapsed IOL; PCNSL or IOL which has only achieved a PR after adequate initial therapy
  • Must have CNS or intraocular involvement by NHL
  • Subjects with secondary CNS NHL, relapsed PCNSL, or relapsed IOL will have received Salvage therapy for their CNS disease
  • Subjects with synchronous CNS NHL will have received primary therapy including CNS-directed therapy
  • Must demonstrate a partial or complete response of the CNS and systemic disease to pre-enrollment therapy, and must be in PR or CR at the time of enrollment
  • Age >/= 18 and </= 75 years
  • Life expectancy >/= 3 months
  • ECOG performance status </= 2
  • Must have adequate organ function as defined by the protocol

Exclusion Criteria:

  • Stable or progressive CNS or systemic disease (SD orPD) at the time of enrollment
  • Systemic or intrathecal chemotherapy or radiotherapy within 2 weeks prior to starting therapy on study
  • Actively receiving any other study agents aimed to treat their disease
  • A prior HDT-ASCT or allogeneic stem cell transplant (myeloablative or nonmyeloablative)
  • Burkitt's lymphoma or acute lymphoblastic lymphoma
  • A history of severe allergic reactions attributed to compounds of similar chemical or biologic composition to cytarabine, thiotepa, busulfan, cyclophosphamide, or rituximab
  • Serious uncontrolled concurrent illness
  • Any evidence of prior exposure to Hepatitis B virus
  • HIV-positive
  • Pregnant or lactating
  • A history of malignancy other than NHL or PCNSL unless disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01182415
Other Study ID Numbers  ICMJE 09-444
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yi-Bin A. Chen, MD, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE
  • Genentech, Inc.
  • Otsuka America Pharmaceutical
  • Dana-Farber Cancer Institute
Investigators  ICMJE
Principal Investigator: Yi-Bin A Chen, MD Massachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP