Background:
Secondary central nervous system lymphoma (sCNSL) is cancer that has spread to the central nervous system. Most drugs used to treat it do not cross the blood-brain barrier. This makes it hard to treat. Researchers hope that a new combination of drugs may be able to help.
Objective:
To find a better way to treat sCNSL.
Eligibility:
People ages 18 and older with sCNSL
Design:
Participants will be screened with:
Participants will take the study drugs in 21-day cycles. They will take some drugs by mouth. They will take others through a catheter: A small tube will be inserted into a vein in the arm, neck, or chest. They may have drugs given through a catheter placed through the brain or injected into the spinal canal.
Participants will have regular visits during the study. These will include repeats of the screening test. They may also provide a saliva sample or have a cheek swab.
Participants will have up to 4 treatment cycles.
Participants will have a follow-up visit 30 days after their last treatment dose. Then they will have visits every 3-6 months for 3 years and then yearly....
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Central Nervous System Lymphoma Secondary Central Nervous System Lymphoma | Drug: TEDD-R Drug: TEDDI-R Drug: Ibrutinib Drug: Cytarabine Drug: Isavuconazole | Phase 2 |
Background:
Objective:
-To estimate the progression-free survival (PFS) after TEDDI-R or TEDD-R in secondary CNS lymphoma (sCNSL)
Eligibility:
Design:
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 65 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Study of Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib, and Rituximab (TEDDI-R) in Aggressive B-cell Lymphomas With Secondary Involvement of the Central Nervous System (CNS) |
Actual Study Start Date : | June 27, 2019 |
Estimated Primary Completion Date : | July 1, 2022 |
Estimated Study Completion Date : | July 1, 2025 |
Arm | Intervention/treatment |
---|---|
Experimental: 1
Temozolomide, etoposide, doxil, dexamethasone, andrituximab without ibrutinib (TEDD-R) or TEDD-R with ibrutinib (TEDDI-R), concurrent with cytarabine and isavuconazole, based upon response to 14-day ibrutinib window
|
Drug: TEDD-R
Temozolomide, etoposide, doxil, dexamthasone, and rituximab (TEDD-R) given every 21 days for cycles 1-4
Drug: TEDDI-R Temozolomide, etoposide, doxil, dexamthasone, ibrutinib and rituximab (TEDDI-R) given every 21 days for cycles 1-4
Drug: Ibrutinib For Arm 1:Ibrutinib given on days -14 to day -1 prior to cycle 1;then given every 21 days for cycles 1-4 For Arm 2: Ibrutinib given on days -14 to day -1 prior to cycle 1; then on days 1-10 for cycles 1-4
Drug: Cytarabine Cytarabine on days 1 and day 5 of cycles 2-5 (all arms)
Drug: Isavuconazole Isavuconazole to begin at least 3 days (and up to 7 days) prior to ibrutinib and continue throughout chemotherapy
|
Experimental: 2
Temozolomide, etoposide, doxil, dexamethasone, and rituximab without ibrutinib (TEDD-R) or TEDD-R with ibrutinib Days 1-10 (TEDDI-R), concurrent with cytarabine and isavuconazole, based upon response to 14-day ibrutinib window
|
Drug: TEDD-R
Temozolomide, etoposide, doxil, dexamthasone, and rituximab (TEDD-R) given every 21 days for cycles 1-4
Drug: TEDDI-R Temozolomide, etoposide, doxil, dexamthasone, ibrutinib and rituximab (TEDDI-R) given every 21 days for cycles 1-4
Drug: Ibrutinib For Arm 1:Ibrutinib given on days -14 to day -1 prior to cycle 1;then given every 21 days for cycles 1-4 For Arm 2: Ibrutinib given on days -14 to day -1 prior to cycle 1; then on days 1-10 for cycles 1-4
Drug: Cytarabine Cytarabine on days 1 and day 5 of cycles 2-5 (all arms)
Drug: Isavuconazole Isavuconazole to begin at least 3 days (and up to 7 days) prior to ibrutinib and continue throughout chemotherapy
|
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
NOTE: B-cell lymphomas that were previously indolent but now involve the CNS (i.e. transformed from previous follicular lymphoma or chronic lymphocytic leukemia and mantle cell lymphoma) are eligible.
Participants must have adequate organ function as defined below, independent of growth factor or platelet transfusion support:
The effects of ibrutinib and TEDDI-R on the developing human fetus are unknown. For this reason, male and female participants must agree to use highly effective methods of birth control. A "highly effective method of birth control" is defined as a method that has a low failure rate (i.e., less than 1% per year) when used consistently and correctly and includes implants, injectables, birth control pills with two hormones, some intrauterine devices (IUDs). Male participants cannot use highly effective methods and are required to use barrier. The specific guidelines are as follows:
EXCLUSION CRITERIA:
NOTE: In addition, because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list; medical reference texts such as the Physicians Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the participants will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participants is considering a new over-the-counter medicine or herbal product.
History of prior malignancy, with the exception of the following:
Contact: NCI Medical Oncology Referral Office | (240) 760-6050 | ncimo_referrals@nih.gov |
United States, Maryland | |
National Institutes of Health Clinical Center | Recruiting |
Bethesda, Maryland, United States, 20892 | |
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937 |
Principal Investigator: | Mark J Roschewski, M.D. | National Cancer Institute (NCI) |
Tracking Information | |||||
---|---|---|---|---|---|
First Submitted Date ICMJE | May 24, 2019 | ||||
First Posted Date ICMJE | May 28, 2019 | ||||
Last Update Posted Date | June 9, 2021 | ||||
Actual Study Start Date ICMJE | June 27, 2019 | ||||
Estimated Primary Completion Date | July 1, 2022 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Progression-free survival (PFS) [ Time Frame: every 3-6 months ] time from study enrollment until disease progression or death from any cause
|
||||
Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
|
||||
Original Secondary Outcome Measures ICMJE |
|
||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib, and Rituximab (TEDDI-R) in Aggressive B-cell Lymphomas With Secondary Involvement of the Central Nervous System (CNS) | ||||
Official Title ICMJE | A Study of Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib, and Rituximab (TEDDI-R) in Aggressive B-cell Lymphomas With Secondary Involvement of the Central Nervous System (CNS) | ||||
Brief Summary |
Background: Secondary central nervous system lymphoma (sCNSL) is cancer that has spread to the central nervous system. Most drugs used to treat it do not cross the blood-brain barrier. This makes it hard to treat. Researchers hope that a new combination of drugs may be able to help. Objective: To find a better way to treat sCNSL. Eligibility: People ages 18 and older with sCNSL Design: Participants will be screened with:
Participants will take the study drugs in 21-day cycles. They will take some drugs by mouth. They will take others through a catheter: A small tube will be inserted into a vein in the arm, neck, or chest. They may have drugs given through a catheter placed through the brain or injected into the spinal canal. Participants will have regular visits during the study. These will include repeats of the screening test. They may also provide a saliva sample or have a cheek swab. Participants will have up to 4 treatment cycles. Participants will have a follow-up visit 30 days after their last treatment dose. Then they will have visits every 3-6 months for 3 years and then yearly.... |
||||
Detailed Description |
Background:
Objective: -To estimate the progression-free survival (PFS) after TEDDI-R or TEDD-R in secondary CNS lymphoma (sCNSL) Eligibility:
Design:
|
||||
Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
||||
Condition ICMJE |
|
||||
Intervention ICMJE |
|
||||
Study Arms ICMJE |
|
||||
Publications * | Not Provided | ||||
* 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 | Recruiting | ||||
Estimated Enrollment ICMJE |
65 | ||||
Original Estimated Enrollment ICMJE |
32 | ||||
Estimated Study Completion Date ICMJE | July 1, 2025 | ||||
Estimated Primary Completion Date | July 1, 2022 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
NOTE: B-cell lymphomas that were previously indolent but now involve the CNS (i.e. transformed from previous follicular lymphoma or chronic lymphocytic leukemia and mantle cell lymphoma) are eligible.
EXCLUSION CRITERIA:
NOTE: In addition, because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list; medical reference texts such as the Physicians Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the participants will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participants is considering a new over-the-counter medicine or herbal product.
|
||||
Sex/Gender ICMJE |
|
||||
Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
|
||||
Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03964090 | ||||
Other Study ID Numbers ICMJE | 190103 19-C-0103 |
||||
Has Data Monitoring Committee | Not Provided | ||||
U.S. FDA-regulated Product |
|
||||
IPD Sharing Statement ICMJE | Not Provided | ||||
Responsible Party | National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ) | ||||
Study Sponsor ICMJE | National Cancer Institute (NCI) | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
|
||||
PRS Account | National Institutes of Health Clinical Center (CC) | ||||
Verification Date | February 19, 2021 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |