Primary Central Nervous System LymphomaPhase 1NCT02203526
Phase 1 Study of Ibrutinib and Immuno-Chemotherapy Using Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib,Rituximab (TEDDI-R) in Primary CNS Lymphoma
A Phase 1 study testing Isavuconazole, TEDDI and Rituximab in people with Primary Central Nervous System Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
BACKGROUND: Primary CNS lymphoma (PCNSL) is a rare subtype of diffuse large B-cell lymphoma. The outcome for patients with this diagnosis is significantly worse than for that of systemic DLBCL. Most treatment approaches in the past have included high dose methotrexate and radiation treatment. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Primary Central Nervous System Lymphoma
- What is being tested?
- Isavuconazole, TEDDI and Rituximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Aug 2014to 15 Jun 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Prior exposure to a BTK inhibitor.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib or other agents used in study.
- Patients who are allergic to isavuconazole or any of its ingredients.
- Patients who received a strong cytochrome P450 (CYP) 3A inhibitor or inducer within 7 days prior to the first dose of protocol anti-fungal prophylaxis, or patients who require continuous treatment with a strong CYP3A inhibitor/inducer (i.e., with the exception of any medication to be specifically studied in this protocol).
- 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 patient 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 patient is considering a new over-the-counter medicine or herbal product.
- HIV positive patients will be excluded because of their increased susceptibility to fungal infections which outweighs the potential benefit of participation.
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- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or an infection requiring systemic antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Recent infections requiring systemic treatment need to have completed therapy >14 days before the first dose of study drug.
- Pregnant and nursing individuals are excluded from this study. Pregnant individuals are excluded in this study because ibrutinib is a tyrosine kinase inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of with a nursing participant ibrutinib, nursing should be discontinued if the mother is treated with ibrutinib.
- Uncontrolled Autoimmune Hemolytic Anemia or ITP resulting in (or as evidenced by) declining platelet or Hgb levels within the 4 weeks prior to first dose of study drug.
- Presence of transfusion-dependent thrombocytopenia.
- History of prior malignancy, with the exception of the following:
- Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to Screening and felt to be at low risk for recurrence by treating physician
- Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
- Adequately treated carcinoma in situ without current evidence of disease.
- Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification, or history of myocardial infarction unstable angina, or acute coronary syndrome within 6 months prior to enrollment in the study.
- Unable to swallow capsules, or disease significantly affecting gastrointestinal function or resection of the stomach or small bowel, or symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
- Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. Those who are PCR positive will be excluded. Those with a negative PCR for hepatitis B will be treated with antivirals designed to prevent hepatitis B reactivation (e.g., entecavir) and have monitoring for hepatitis B reactivation with PCR.
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- Any life-threatening illness, medical condition, or organ system dysfunction that, in the Investigator's opinion, could compromise the patient's safety, or put the study at undue risk. Patients with suspicious radiologic evidence of aspergillosis infection (i.e., Chest CT and/or Brain MRI) will not be eligible unless confirmatory laboratory testing of Beta-D glucan and aspergillus antigen are negative.
- Concomitant use of warfarin or other vitamin K antagonists within the last 7 days.
- Concurrent systemic immunosuppressant therapy other than corticosteroids (e.g., cyclosporine A, tacrolimus, etc.) within 28 days of the first dose of study drug.
- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
- Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to grade <=1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia.
- Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.
- Major surgery within 7 days of first dose of study drug.
- Unwilling or unable to participate in all required study evaluations and procedures.
- Currently active, clinically significant hepatic impairment (>= moderate hepatic impairment according to the NCI/Child Pugh classification)
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Phase 1 Study of Ibrutinib and Immuno-Chemotherapy Using Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib, Rituximab (TEDDI-R) in Primary CNS Lymphoma
BACKGROUND:
- Primary CNS lymphoma (PCNSL) is a rare subtype of diffuse large B-cell lymphoma.
- The outcome for patients with this diagnosis is significantly worse than for that of systemic DLBCL. Most treatment approaches in the past have included high dose methotrexate and radiation treatment.
- Most PCNSLs appear to be of activated B-cell (ABC) origin.
- Ibrutinib is an inhibitor of Bruton s tyrosine kinase (BTK) and effective for systemic DLBCL of ABC origin.
- We propose doing a study in which ibrutinib is combined with a novel chemotherapy platform called dose adjusted temozolomide, etoposide, doxil, dexamethasone, ibrutinib, rituximab (TEDDI-R).
Read more
OBJECTIVE:
- Identify the maximum tolerated dose (MTD) of ibrutinib or the dose that achieves adequate CSF concentrations, whichever comes first, when ibrutinib is given with TEDDI-R.
ELIGIBILITY:
- Relapsed/refractory PCNSL.
- Age greater than or equal to 18 years.
- No pregnant or breast-feeding women.
- Adequate organ function (defined in protocol).
STUDY DESIGN:
- This is a phase 1 study of 40 patients.
- The study will have two components.
- Phase 1: MTD of ibrutinib will be identified or the dose at which ibrutinib achieves a concentration of less than or equal to 100 nM in the CSF, when given in combination with TEDDI-R immuno-chemotherapy, whichever comes first.
- Expansion cohort: Safety and tolerability of the regimen in relapsed/refractory or previously untreated PCNSL (DLBCL type) will be assessed at the final ibrutinib dose with TEDDI-R in 10 patients. Secondary objectives will be PFS and OS.
Read the detailed description
Background:
- Primary CNS lymphoma (PCNSL) is a rare subtype of diffuse large B-cell lymphoma
- The outcome for patients with this diagnosis is significantly worse than for that of systemic DLBCL. Most treatment approaches in the past have included high dose methotrexate and radiation treatment.
- Most PCNSLs appear to be of activated B-cell (ABC) origin
- Ibrutinib is an inhibitor of Bruton's tyrosine kinase (BTK) and effective for systemic DLBCL of ABC origin.
- We propose doing a study in which ibrutinib is combined with a novel chemotherapy platform called temozolomide, etoposide, doxil, dexamethasone, ibrutinib, rituximab (TEDDI-R).
Objective:
- To identify the dose of ibrutinib with anti-fungal prophylaxis that can be safely administered to achieve an ibrutinib median CSF CMAX of 1.98 nM (Range 0.69 to 11.1)
- To assess the safety, feasibility, and complete response (CR) rate of the TEDDI-R in untreated PCNSL (DLBCL type) patients.
Eligibility:
- Relapsed/refractory or untreated PCNSL
- Age >= 18 years.
- No pregnant or nursing individuals.
- Adequate organ function (defined in protocol).
Study Design:
- This is a phase 1 study of 93 patients.
- The study will have three components.
- Phase 1: MTD of ibrutinib will be identified or the dose at which ibrutinib achieves a concentration of >= 100 nM in the CSF, when given in combination with TEDDI-R immuno-chemotherapy, whichever comes first.
- Expansion cohort: Safety and tolerability of the regimen in relapsed/refractory PCNSL (DLBCL type) will be assessed at the final ibrutinib dose with TEDDI-R in 10 patients. Secondary objectives will be PFS and OS.
- Revised Study Design: new ibrutinib dose levels are being added together with anti-fungal prophylaxis to determine the dose of ibrutinib that may be safely given with the chemotherapy platform.
- A second expansion cohort of untreated PCNSL (DLBCL type) will be added: Safety, feasibility, and complete response rate of the regimen in untreated PCNSL (DLBCL type) will be assessed at the final ibrutinib dose with TEDDI-R in 15 patients. Secondary objectives will be PFS and OS.
- A new dosing schedule will be tested in up to 10 relapsed or refractory patients and 15 patients with untreated PCNSL. Secondary objectives will be PFS and OS.
- Conditions
- Primary Central Nervous System Lymphoma
- Being tested
- Isavuconazole, TEDDI, Rituximab, Cytarabine, TEDD
- Keywords
- Tyrosine Kinase Inhibitor, ABC DLCBL, Lymphoma in Brain and CNS, Diffuse Large B-Cell Lymphomas in CNS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsavuconazoleDrug
Isavuconazole to begin at least 3 days prior to ibrutinib and continue throughout chemotherapy (cycles 1-6)
TEDDIDrug
Temozolomide, etoposide, doxil, dexamthasone, ibrutinib (TEDDI) given every 21 days for cycles 2-6 (Arm 1-A); given every 21 days for cycles 1-6 (Arms 1-B, 2, 3 and 4)
RituximabBiological
Rituximab (R) given with TEDD and TEDDI every 3 weeks for cycles 1-6 (all arms)
CytarabineDrug
Cytarabine given via Ommaya reservoir (IT therapy) on days 1 and day 5 of cycles 2-6 (all arms)
TEDDDrug
Temozolomide, etoposide, doxil, dexamthasone, (TEDD) given on first cycle (Arm 1-A)
Ibrutinib (Arms 2, 3 and 4)Drug
Ibrutinib given on day -3 to day -1 on cycle 1 (Arms 2, 3 and 4)
MethotrexateDrug
Methotrexate on days 1 and day 5 of cycles 2-6 (Arm 4)
Ibrutinib (Arm 1 - Closed with Amendment G)Drug
Ibrutinib given on day -14 to day -1 on cycle 1 (Arm 1)
Ibrutinib (Arm 4)Drug
Ibrutinib given on days 1-10 for cycles 1-6 (Arm 4)
| Study group | Role | What they receive |
|---|---|---|
| Arm 1-A (original study design - prior to Amendment G) | Experimental | TEDD-R (cycle 1) with ibrutinib; TEDDI-R with cytarabine (cycles 2-6) Receives: Drug: TEDDI; Biological: Rituximab; Drug: Cytarabine; Drug: TEDD; Drug: Ibrutinib (Arms 2, 3 and 4); Drug: Ibrutinib (Arm 1 - Closed with Amendment G); Drug: Ibrutinib (Arm 4) |
| Arm 1-B (original study design-prior to Amendment G) | Experimental | TEDDI-R with cytarabine Receives: Drug: TEDDI; Biological: Rituximab; Drug: Cytarabine |
| Arm 2 (Dose Escalation; prior to Amendment 06/04/2021) | Experimental | TEDDI-R with cytarabine, and isavuconazole Receives: Drug: Isavuconazole; Drug: TEDDI; Biological: Rituximab; Drug: Cytarabine |
| Arm 3 (Dose Expansion; prior to Amendment 06/04/2021) | Experimental | TEDDI-R with cytarabine and isavuconazole Receives: Drug: Isavuconazole; Drug: TEDDI; Biological: Rituximab; Drug: Cytarabine |
| Arm 4 (Dose Expansion; Amendment 06/04/21) | Experimental | TEDDI-R, cytarabine or methotrexate, isavuconazole, ibrutinib for 10 days Receives: Drug: Isavuconazole; Drug: TEDDI; Biological: Rituximab; Drug: Cytarabine; Drug: Methotrexate; Drug: Ibrutinib (Arm 4) |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety and feasibility in untreated PCNSL patients
Incidence of adverse events (i.e., grade and frequency)
Measured: Initiation of ibrutinib until 30 days after treatment
MTD of ibrutinib with anti-fungal prophylaxis when given with TEDD-R
AEs will be tabulated and reported
Measured: after one cycle
MTD of ibrutinib when given with TEDD-R
AEs will be tabulated and reported
Measured: after one cycle
Complete Response rate in untreated PCNSL patients
The response rate will be determined and reported along with a 95% confidence interval
Measured: every 3 months for 1 year, every 4 months year 2, every 6 months year 3 then yearly
Secondary outcomes (3)
Safety and Tolerability
Incidence of adverse events (i.e., grade and frequency)
Measured: Initiation of ibrutinib until 30 days after treatment
Progression-free survival
The response rate will be determined and reported along with a 95% confidence interval
Measured: every 3 months for 1 year, every 4 months year 2, every 6 months year 3 then yearly
Overall survival
The response rate will be determined and reported along with a 95% confidence interval
Measured: every 3 months for 1 year, every 4 months year 2, every 6 months year 3 then yearly
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2014 (estimated)
- Study start14 Aug 2014
- Primary completion30 Jul 2026
- Study completion15 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Central Nervous System LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Rahul Lakhotia, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02203526
- Sponsor's protocol ID
- 140157
- Other IDs
- 14-C-0157
- Status last verified
- 28 Sep 2026
- First submitted
- 29 Jul 2014
- Last updated
- 30 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@@@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP. @@@@@@@@@@@@All collected IPD will be shared with collaborators under the terms of collaborative agreements.
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Ibrutinib and Immuno-Chemotherapy Using Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib, Rituximab (TEDDI-R) in Primary CNS Lymphoma
- ClinicalTrials.gov ID
- NCT02203526
- Acronym / sponsor ID
- 140157
- Conditions
- Primary Central Nervous System Lymphoma
- Keywords
- Tyrosine Kinase Inhibitor, ABC DLCBL, Lymphoma in Brain and CNS, Diffuse Large B-Cell Lymphomas in CNS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 68 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 14 Aug 2014 (actual)
- Primary completion
- 30 Jul 2026 (actual)
- Study completion
- 15 Jun 2028 (estimated)
- First posted
- 30 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
BACKGROUND:
- Primary CNS lymphoma (PCNSL) is a rare subtype of diffuse large B-cell lymphoma.
- The outcome for patients with this diagnosis is significantly worse than for that of systemic DLBCL. Most treatment approaches in the past have included high dose methotrexate and radiation treatment.
- Most PCNSLs appear to be of activated B-cell (ABC) origin.
- Ibrutinib is an inhibitor of Bruton s tyrosine kinase (BTK) and effective for systemic DLBCL of ABC origin.
- We propose doing a study in which ibrutinib is combined with a novel chemotherapy platform called dose adjusted temozolomide, etoposide, doxil, dexamethasone, ibrutinib, rituximab (TEDDI-R).
OBJECTIVE:
- Identify the maximum tolerated dose (MTD) of ibrutinib or the dose that achieves adequate CSF concentrations, whichever comes first, when ibrutinib is given with TEDDI-R.
ELIGIBILITY:
- Relapsed/refractory PCNSL.
- Age greater than or equal to 18 years.
- No pregnant or breast-feeding women.
- Adequate organ function (defined in protocol).
STUDY DESIGN:
- This is a phase 1 study of 40 patients.
- The study will have two components.
- Phase 1: MTD of ibrutinib will be identified or the dose at which ibrutinib achieves a concentration of less than or equal to 100 nM in the CSF, when given in combination with TEDDI-R immuno-chemotherapy, whichever comes first.
- Expansion cohort: Safety and tolerability of the regimen in relapsed/refractory or previously untreated PCNSL (DLBCL type) will be assessed at the final ibrutinib dose with TEDDI-R in 10 patients. Secondary objectives will be PFS and OS.
Detailed description
Background:
- Primary CNS lymphoma (PCNSL) is a rare subtype of diffuse large B-cell lymphoma
- The outcome for patients with this diagnosis is significantly worse than for that of systemic DLBCL. Most treatment approaches in the past have included high dose methotrexate and radiation treatment.
- Most PCNSLs appear to be of activated B-cell (ABC) origin
- Ibrutinib is an inhibitor of Bruton's tyrosine kinase (BTK) and effective for systemic DLBCL of ABC origin.
- We propose doing a study in which ibrutinib is combined with a novel chemotherapy platform called temozolomide, etoposide, doxil, dexamethasone, ibrutinib, rituximab (TEDDI-R).
Objective:
- To identify the dose of ibrutinib with anti-fungal prophylaxis that can be safely administered to achieve an ibrutinib median CSF CMAX of 1.98 nM (Range 0.69 to 11.1)
- To assess the safety, feasibility, and complete response (CR) rate of the TEDDI-R in untreated PCNSL (DLBCL type) patients.
Eligibility:
- Relapsed/refractory or untreated PCNSL
- Age >= 18 years.
- No pregnant or nursing individuals.
- Adequate organ function (defined in protocol).
Study Design:
- This is a phase 1 study of 93 patients.
- The study will have three components.
- Phase 1: MTD of ibrutinib will be identified or the dose at which ibrutinib achieves a concentration of >= 100 nM in the CSF, when given in combination with TEDDI-R immuno-chemotherapy, whichever comes first.
- Expansion cohort: Safety and tolerability of the regimen in relapsed/refractory PCNSL (DLBCL type) will be assessed at the final ibrutinib dose with TEDDI-R in 10 patients. Secondary objectives will be PFS and OS.
- Revised Study Design: new ibrutinib dose levels are being added together with anti-fungal prophylaxis to determine the dose of ibrutinib that may be safely given with the chemotherapy platform.
- A second expansion cohort of untreated PCNSL (DLBCL type) will be added: Safety, feasibility, and complete response rate of the regimen in untreated PCNSL (DLBCL type) will be assessed at the final ibrutinib dose with TEDDI-R in 15 patients. Secondary objectives will be PFS and OS.
- A new dosing schedule will be tested in up to 10 relapsed or refractory patients and 15 patients with untreated PCNSL. Secondary objectives will be PFS and OS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Arm 1-A (original study design - prior to Amendment G) | Experimental | Drug: TEDDI, Biological: Rituximab, Drug: Cytarabine, Drug: TEDD, Drug: Ibrutinib (Arms 2, 3 and 4), Drug: Ibrutinib (Arm 1 - Closed with Amendment G), Drug: Ibrutinib (Arm 4)TEDD-R (cycle 1) with ibrutinib; TEDDI-R with cytarabine (cycles 2-6) |
| Arm 1-B (original study design-prior to Amendment G) | Experimental | Drug: TEDDI, Biological: Rituximab, Drug: CytarabineTEDDI-R with cytarabine |
| Arm 2 (Dose Escalation; prior to Amendment 06/04/2021) | Experimental | Drug: Isavuconazole, Drug: TEDDI, Biological: Rituximab, Drug: CytarabineTEDDI-R with cytarabine, and isavuconazole |
| Arm 3 (Dose Expansion; prior to Amendment 06/04/2021) | Experimental | Drug: Isavuconazole, Drug: TEDDI, Biological: Rituximab, Drug: CytarabineTEDDI-R with cytarabine and isavuconazole |
| Arm 4 (Dose Expansion; Amendment 06/04/21) | Experimental | Drug: Isavuconazole, Drug: TEDDI, Biological: Rituximab, Drug: Cytarabine, Drug: Methotrexate, Drug: Ibrutinib (Arm 4)TEDDI-R, cytarabine or methotrexate, isavuconazole, ibrutinib for 10 days |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (27 listed)
- Prior exposure to a BTK inhibitor.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib or other agents used in study.
- Patients who are allergic to isavuconazole or any of its ingredients.
- Patients who received a strong cytochrome P450 (CYP) 3A inhibitor or inducer within 7 days prior to the first dose of protocol anti-fungal prophylaxis, or patients who require continuous treatment with a strong CYP3A inhibitor/inducer (i.e., with the exception of any medication to be specifically studied in this protocol).
- 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 patient 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 patient is considering a new over-the-counter medicine or herbal product.
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 |
|---|---|---|
| IsavuconazoleIsavuconazole to begin at least 3 days prior to ibrutinib and continue throughout chemotherapy (cycles 1-6) | Drug | Arm 2 (Dose Escalation; prior to Amendment 06/04/2021), Arm 3 (Dose Expansion; prior to Amendment 06/04/2021), Arm 4 (Dose Expansion; Amendment 06/04/21) |
| TEDDITemozolomide, etoposide, doxil, dexamthasone, ibrutinib (TEDDI) given every 21 days for cycles 2-6 (Arm 1-A); given every 21 days for cycles 1-6 (Arms 1-B, 2, 3 and 4) | Drug | Arm 1-A (original study design - prior to Amendment G), Arm 1-B (original study design-prior to Amendment G), Arm 2 (Dose Escalation; prior to Amendment 06/04/2021), Arm 3 (Dose Expansion; prior to Amendment 06/04/2021), Arm 4 (Dose Expansion; Amendment 06/04/21) |
| RituximabRituximab (R) given with TEDD and TEDDI every 3 weeks for cycles 1-6 (all arms) | Biological | Arm 1-A (original study design - prior to Amendment G), Arm 1-B (original study design-prior to Amendment G), Arm 2 (Dose Escalation; prior to Amendment 06/04/2021), Arm 3 (Dose Expansion; prior to Amendment 06/04/2021), Arm 4 (Dose Expansion; Amendment 06/04/21) |
| CytarabineCytarabine given via Ommaya reservoir (IT therapy) on days 1 and day 5 of cycles 2-6 (all arms) | Drug | Arm 1-A (original study design - prior to Amendment G), Arm 1-B (original study design-prior to Amendment G), Arm 2 (Dose Escalation; prior to Amendment 06/04/2021), Arm 3 (Dose Expansion; prior to Amendment 06/04/2021), Arm 4 (Dose Expansion; Amendment 06/04/21) |
| TEDDTemozolomide, etoposide, doxil, dexamthasone, (TEDD) given on first cycle (Arm 1-A) | Drug | Arm 1-A (original study design - prior to Amendment G) |
| Ibrutinib (Arms 2, 3 and 4)Ibrutinib given on day -3 to day -1 on cycle 1 (Arms 2, 3 and 4) | Drug | Arm 1-A (original study design - prior to Amendment G) |
| MethotrexateMethotrexate on days 1 and day 5 of cycles 2-6 (Arm 4) | Drug | Arm 4 (Dose Expansion; Amendment 06/04/21) |
| Ibrutinib (Arm 1 - Closed with Amendment G)Ibrutinib given on day -14 to day -1 on cycle 1 (Arm 1) | Drug | Arm 1-A (original study design - prior to Amendment G) |
| Ibrutinib (Arm 4)Ibrutinib given on days 1-10 for cycles 1-6 (Arm 4) | Drug | Arm 1-A (original study design - prior to Amendment G), Arm 4 (Dose Expansion; Amendment 06/04/21) |
Primary outcome
safety and feasibility in untreated PCNSL patients
Time frame: Initiation of ibrutinib until 30 days after treatment
Incidence of adverse events (i.e., grade and frequency)
MTD of ibrutinib with anti-fungal prophylaxis when given with TEDD-R
Time frame: after one cycle
AEs will be tabulated and reported
MTD of ibrutinib when given with TEDD-R
Time frame: after one cycle
AEs will be tabulated and reported
Complete Response rate in untreated PCNSL patients
Time frame: every 3 months for 1 year, every 4 months year 2, every 6 months year 3 then yearly
The response rate will be determined and reported along with a 95% confidence interval
3 secondary outcomes
Safety and Tolerability
Time frame: Initiation of ibrutinib until 30 days after treatment
Progression-free survival
Time frame: every 3 months for 1 year, every 4 months year 2, every 6 months year 3 then yearly
Overall survival
Time frame: every 3 months for 1 year, every 4 months year 2, every 6 months year 3 then yearly
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@@@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP. @@@@@@@@@@@@All collected IPD will be shared with collaborators under the terms of collaborative agreements.
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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.
Rahul Lakhotia, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Isavuconazole, TEDDI and Rituximab in people with Primary Central Nervous System Lymphoma, run by National Cancer Institute (NCI) at 1 site 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 0 inclusion and 27 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: under way, not looking for participants, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
safety and feasibility in untreated PCNSL patients (time frame: Initiation of ibrutinib until 30 days after treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Sep 2026.