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

NCT01182415 | Completed Phase 2 Results DMC

• 1 other identifier: 09-444
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Non-Hodgkin's Lymphoma; CNS Lymphoma

Keywords

CNS involvement

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients With CNS Involvement by B-cell NHL, Relapsed PCNSL, or Relapsed PIOL Who Are Alive and Progression-free at One Year

  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.

  3 years

Secondary Outcomes (3)

• 2-year Progression Free Survival (PFS)

  2 years

• 2-year Overall Survival (OS)

  2 years

• Response Rate

  3 years

Study Arms (1)

High-dose chemotherapy with autologous stem cell transplant

EXPERIMENTAL

Procedure: Autologous stem cell transplant; Drug: High-dose chemotherapy

Interventions

Autologous stem cell transplant PROCEDURE

Autologous stem cell transplant following high-dose chemotherapy

High-dose chemotherapy with autologous stem cell transplant

High-dose chemotherapy DRUG

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

High-dose chemotherapy with autologous stem cell transplant

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Genentech, Inc.: collaborator
• Otsuka America Pharmaceutical: collaborator
• Dana-Farber Cancer Institute: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• 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.

  PMID: 25204639 RESULT

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

• Title: Dr. Yi-Bin Chen
• Organization: Massachusetts General Hospital

YCHEN6@PARTNERS.ORG

617-726-0187

Study Officials

• Yi-Bin A Chen, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 30, 2010
• First Posted: August 16, 2010
• Study Start: June 1, 2010
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2016
• Last Updated: April 6, 2023
• Results First Posted: December 29, 2017

Record last verified: 2023-03

Locations

US (2)