Non-Hodgkin's LymphomaPhase 2NCT01182415
High Dose Chemotherapy and Stem Cell Transplant for Non-Hodgkin's Lymphoma or Central Nervous System (CNS) Lymphoma
A Phase 2 study testing Autologous stem cell transplant and High-dose chemotherapy in people with Non-Hodgkin's Lymphoma and CNS Lymphoma, run by Massachusetts General Hospital at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-Hodgkin's Lymphoma, CNS Lymphoma
- What is being tested?
- Autologous stem cell transplant and High-dose chemotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2010to Dec 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Life expectancy >/= 3 months
- ECOG performance status </= 2
- Must have adequate organ function as defined by the protocol
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: 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
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.
Read more
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.
Read the 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.
- Conditions
- Non-Hodgkin's Lymphoma, CNS Lymphoma
- Being tested
- Autologous stem cell transplant, High-dose chemotherapy
- Keywords
- CNS involvement
- Medical subject headings
- Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous stem cell transplantProcedure or surgery
Autologous stem cell transplant following high-dose chemotherapy
High-dose chemotherapyDrug
High-dose chemotherapy with rituximab, thiotepa, busulfan, and cyclosphosphamide
| Study group | Role | What they receive |
|---|---|---|
| High-dose chemotherapy with autologous stem cell transplant | Experimental | Not described Receives: Procedure: Autologous stem cell transplant; Drug: High-dose chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Secondary outcomes (3)
2-year Progression Free Survival (PFS)
The percentage of participants alive and without disease progression at 2 years. Disease progression was judged through clinical impression and MRI imaging.
Measured: 2 years
2-year Overall Survival (OS)
The percentage of participants alive after two years
Measured: 2 years
Response Rate
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.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2010 (estimated)
- Study startJun 2010
- Primary completionDec 2015
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-Hodgkin's LymphomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., Otsuka America Pharmaceutical, Dana-Farber Cancer Institute
- Responsible party
- Principal investigator, Yi-Bin A. Chen, MD, Massachusetts General Hospital
- Investigators
- Yi-Bin A Chen, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01182415
- Sponsor's protocol ID
- 09-444
- Status last verified
- Mar 2023
- First submitted
- 30 Apr 2010
- Last updated
- 6 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 25204639
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01182415
- Acronym / sponsor ID
- 09-444
- Conditions
- Non-Hodgkin's Lymphoma, CNS Lymphoma
- Keywords
- CNS involvement
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Genentech, Inc., Otsuka America Pharmaceutical, Dana-Farber Cancer Institute
- Study start
- Jun 2010
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 16 Aug 2010 (estimated)
- Results
- Posted 29 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| High-dose chemotherapy with autologous stem cell transplant | Experimental | Procedure: Autologous stem cell transplant, Drug: High-dose chemotherapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous stem cell transplantAutologous stem cell transplant following high-dose chemotherapy | Procedure or surgery | High-dose chemotherapy with autologous stem cell transplant |
| High-dose chemotherapyHigh-dose chemotherapy with rituximab, thiotepa, busulfan, and cyclosphosphamide | Drug | High-dose chemotherapy with autologous stem cell transplant |
Primary outcome
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. Relapse was defined as per standard PCNSL criteria from clinical and MRI criteria.
3 secondary outcomes
2-year Progression Free Survival (PFS)
Time frame: 2 years
2-year Overall Survival (OS)
Time frame: 2 years
Response Rate
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25204639Chen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yi-Bin A Chen, MD principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Autologous stem cell transplant and High-dose chemotherapy in people with Non-Hodgkin's Lymphoma and CNS Lymphoma, run by Massachusetts General Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01182415, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2023.