Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib, and Rituximab (TEDDI-R) in Aggressive B-cell Lymphomas With Secondary Involvement of the Central Nervous System (CNS)
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|ClinicalTrials.gov Identifier: NCT03964090|
Recruitment Status : Recruiting
First Posted : May 27, 2019
Last Update Posted : August 15, 2019
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.
To find a better way to treat sCNSL.
People ages 18 and older with sCNSL
Participants will be screened with:
- Medical history
- Physical exam
- Blood, urine, and heart tests
- Eye exam
- Tissue or tumor biopsy
- Collection of cerebrospinal fluid
- CT, PET, and MRI scans: Participants will like in a machine that takes pictures of the body.
- Bone marrow aspirations or biopsies: A needle will be inserted into the participant s hipbone. The needle will remove a small amount of marrow.
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|
- Aggressive B-cell lymphomas with secondary involvement of the CNS (sCNSL) have a grave prognosis
- No standard of care exists for sCNSL; treatment approaches include combination chemotherapy regimens effective in primary CNS lymphoma (PCNSL)
- Ibrutinib is an inhibitor of Bruton s tyrosine kinase (BTK) and has demonstrated a high response rate in PCNSL and sCNSL but with short response duration
- We developed a novel regimen that combines ibrutinib with a chemoimmunotherapy platform maximized for CNS penetrance that includes temozolomide, etoposide, Doxil, dexamethasone, and rituximab (TEDDI-R) for aggressive B-cell lymphomas in the CNS
- A phase 1 study of TEDDI-R demonstrated durable remissions in refractory PCNSL
- We propose a small phase 2 to study the safety and efficacy of TEDDI-R in sCNSL
-To estimate the progression-free survival (PFS) after TEDDI-R or TEDD-R in secondary CNS lymphoma (sCNSL)
- Aggressive B-cell lymphomas with secondary involvement of the CNS (sCNSL)
- Relapsed/refractory from prior therapy or untreated with CNS parenchymal lesions
- Age greater than or equal to 18 years
- No pregnant or breast-feeding women.
- Adequate organ function (defined in protocol)
- Phase II study of 29 evaluable patients with untreated and relapsed/refractory sCNSL (accrual ceiling will be set at 32 to allow for a few possible inevaluable patients)
- Patients will first be treated with a 14-day "window" of ibrutinib monotherapy in combination with isavuconazole to establish efficacy of ibrutinib. Patients who are known refractory to BTK inhibitors will skip the 14-day and proceed on to chemotherapy.
- Following the 14-day ibrutinib window, patients with at least a 20% reduction in bidimensional masses on imaging scans or those without measurable disease will receive ibrutinib with TEDD-R (TEDDI-R) chemotherapy for 4 cycles. Patients who are previously known to be refractory to BTK inhibitors and those who have less than a 20% reduction during the ibrutinib window will receive TEDD-R (without ibrutinib) for 4 cycles.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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, 2021|
|Estimated Study Completion Date :||July 1, 2025|
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
Temozolomide, etoposide, doxil, dexamthasone, and rituximab (TEDD-R) given every 21 days for cycles 1-4
Temozolomide, etoposide, doxil, dexamthasone, ibrutinib and rituximab (TEDDI-R) given every 21 days for cycles 1-4
Ibrutinib given on days -14 to day -1 prior to cycle 1
Cytarabine on days 1 and day 5 of cycles 2-6 (all arms)
Isavuconazole to begin at least 3 days (and up to 7 days) prior to ibrutinib and continue throughout chemotherapy
- Progression-free survival (PFS) [ Time Frame: every 3-6 months ]time from study enrollment until disease progression or death from any cause
- Safety and tolerability of TEDDI-R and TEDD-R in sCNSL [ Time Frame: ongoing ]the proportion of patients with adverse events leading to discontinuation of therapy
- Best overall response after 14 days of ibrutinib monotherapy in sCNSL; after up to 4 cycles of TEDDI-R; and, after up to 4 cycles of TEDD-R (no ibrutinib) [ Time Frame: after 14 days and 4 cycles ]proportion of patients who achieve at least a partial response (PR) to therapy
- Duration of response (DOR) [ Time Frame: every 2 cycles during treatment; every 3-6 months in follow-up ]time from first documentation of tumor response to disease progression
- Assessment of pharmacokinetics (PK) and safety of TEDDI-R with concomitant anti-fungal prophylaxis [ Time Frame: at least each cycle, up to cycle 4 ]time from study enrollment until disease progression or death from any cause
- Overall survival (OS) to TEDDI-R and TEDD-R in sCNSL [ Time Frame: every 3-6 months ]time from study enrollment until death from any cause
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03964090
|Contact: Maureen E Edgerly, R.N.||(240) email@example.com|
|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)|