High Dose Chemotherapy and Stem Cell Transplant for Non-Hodgkin's Lymphoma or Central Nervous System (CNS) Lymphoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: High-dose chemotherapy with autologous stem cell transplant
|
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
|
Outcome Measures
Primary Outcome Measures
- Proportion of Patients With CNS Involvement by B-cell NHL, Relapsed PCNSL, or Relapsed PIOL Who Are Alive and Progression-free at One Year [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
Secondary Outcome Measures
- 2-year Progression Free Survival (PFS) [2 years]
The percentage of participants alive and without disease progression at 2 years.
- 2-year Overall Survival (OS) [2 years]
The percentage of participants alive after two years
- Response Rate [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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 2 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
Sponsors and Collaborators
- Massachusetts General Hospital
- Genentech, Inc.
- Otsuka America Pharmaceutical
- Dana-Farber Cancer Institute
Investigators
- Principal Investigator: Yi-Bin A Chen, MD, Massachusetts General Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 09-444
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | High-dose Chemotherapy With Autologous Stem Cell Transplant |
|---|---|
| Arm/Group Description | Autologous stem cell transplant: Autologous stem cell transplant following high-dose chemotherapy High-dose chemotherapy: High-dose chemotherapy with rituximab, thiotepa, busulfan, and cyclosphosphamide |
| Period Title: Overall Study | |
| STARTED | 30 |
| COMPLETED | 29 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | High-dose Chemotherapy With Autologous Stem Cell Transplant |
|---|---|
| Arm/Group Description | Autologous stem cell transplant: Autologous stem cell transplant following high-dose chemotherapy High-dose chemotherapy: High-dose chemotherapy with rituximab, thiotepa, busulfan, and cyclosphosphamide |
| Overall Participants | 30 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
59
|
| Sex: Female, Male (Count of Participants) | |
| Female |
13
43.3%
|
| Male |
17
56.7%
|
| Race and Ethnicity Not Collected (Count of Participants) | |
| Region of Enrollment (participants) [Number] | |
| United States |
30
100%
|
| Histology (Count of Participants) | |
| Diffuse Large B-cell Lymphoma |
27
90%
|
| CLL/ SLL |
2
6.7%
|
| Follicular Non-Hodgkin lymphoma |
1
3.3%
|
| Prior Treatment History (Count of Participants) | |
| High-Dose Intravenous Methotrexate |
29
96.7%
|
| High-Dose Cytarabine |
3
10%
|
| Rituximab (Intravenous) |
30
100%
|
| Whole brain radiation therapy (WBRT) |
2
6.7%
|
| Other Radiation Therapy |
8
26.7%
|
Outcome Measures
| Title | Proportion of Patients With CNS Involvement by B-cell NHL, Relapsed PCNSL, or Relapsed PIOL Who Are Alive and Progression-free at One Year |
|---|---|
| Description | 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 |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participant that was lost to follow-up was not available for analysis. |
| Arm/Group Title | High-dose Chemotherapy With Autologous Stem Cell Transplant |
|---|---|
| Arm/Group Description | Autologous stem cell transplant: Autologous stem cell transplant following high-dose chemotherapy High-dose chemotherapy: High-dose chemotherapy with rituximab, thiotepa, busulfan, and cyclosphosphamide |
| Measure Participants | 29 |
| Count of Participants [Participants] |
28
93.3%
|
| Title | 2-year Progression Free Survival (PFS) |
|---|---|
| Description | The percentage of participants alive and without disease progression at 2 years. |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participant that was lost to follow-up was not available for analysis. |
| Arm/Group Title | High-dose Chemotherapy With Autologous Stem Cell Transplant |
|---|---|
| Arm/Group Description | Autologous stem cell transplant: Autologous stem cell transplant following high-dose chemotherapy High-dose chemotherapy: High-dose chemotherapy with rituximab, thiotepa, busulfan, and cyclosphosphamide |
| Measure Participants | 29 |
| Number (95% Confidence Interval) [percentage of participants] |
81
270%
|
| Title | 2-year Overall Survival (OS) |
|---|---|
| Description | The percentage of participants alive after two years |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participant that was lost to follow-up was not available for analysis. |
| Arm/Group Title | High-dose Chemotherapy With Autologous Stem Cell Transplant |
|---|---|
| Arm/Group Description | Autologous stem cell transplant: Autologous stem cell transplant following high-dose chemotherapy High-dose chemotherapy: High-dose chemotherapy with rituximab, thiotepa, busulfan, and cyclosphosphamide |
| Measure Participants | 29 |
| Number (95% Confidence Interval) [percentage of participants] |
93
310%
|
| Title | Response Rate |
|---|---|
| Description | 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. |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participant that was lost to follow-up was not available for analysis. |
| Arm/Group Title | High-dose Chemotherapy With Autologous Stem Cell Transplant |
|---|---|
| Arm/Group Description | Autologous stem cell transplant: Autologous stem cell transplant following high-dose chemotherapy High-dose chemotherapy: High-dose chemotherapy with rituximab, thiotepa, busulfan, and cyclosphosphamide |
| Measure Participants | 29 |
| Count of Participants [Participants] |
29
96.7%
|
Adverse Events
| Time Frame | From the start of treatment until disease progression, death, or until taken off study; median duration of 24 months. | |
|---|---|---|
| Adverse Event Reporting Description | 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. | |
| Arm/Group Title | High-dose Chemotherapy With Autologous Stem Cell Transplant | |
| Arm/Group Description | Autologous stem cell transplant: Autologous stem cell transplant following high-dose chemotherapy High-dose chemotherapy: High-dose chemotherapy with rituximab, thiotepa, busulfan, and cyclosphosphamide | |
All Cause Mortality |
||
| High-dose Chemotherapy With Autologous Stem Cell Transplant | ||
| Affected / at Risk (%) | # Events | |
| Total | 3/30 (10%) | |
Serious Adverse Events |
||
| High-dose Chemotherapy With Autologous Stem Cell Transplant | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/30 (20%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 2/30 (6.7%) | 2 |
| Febrile neutropenia | 1/30 (3.3%) | 1 |
| Gastrointestinal disorders | ||
| Mucositis oral | 1/30 (3.3%) | 1 |
| General disorders | ||
| Gait disturbance | 1/30 (3.3%) | 1 |
| Infections and infestations | ||
| Lung infection | 1/30 (3.3%) | 1 |
| Investigations | ||
| Alanine aminotransferase increased | 1/30 (3.3%) | 1 |
| Aspartate aminotransferase increased | 1/30 (3.3%) | 1 |
| Lymphocyte count decreased | 1/30 (3.3%) | 2 |
| Platelet count decreased | 2/30 (6.7%) | 2 |
| Investigations - Other, specify | 1/30 (3.3%) | 1 |
| Nervous system disorders | ||
| Encephalopathy | 1/30 (3.3%) | 1 |
| Psychiatric disorders | ||
| Depression | 1/30 (3.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Pneumothorax | 1/30 (3.3%) | 1 |
| Respiratory failure | 1/30 (3.3%) | 1 |
| Vascular disorders | ||
| Hypertension | 1/30 (3.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| High-dose Chemotherapy With Autologous Stem Cell Transplant | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/30 (0%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Yi-Bin Chen |
|---|---|
| Organization | Massachusetts General Hospital |
| Phone | 617-726-0187 |
| YCHEN6@PARTNERS.ORG |
- 09-444