Phase 1 Study of Ibrutinib and Immuno-Chemotherapy Using Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib,Rituximab (TEDDI-R) in Primary CNS Lymphoma

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT02203526
Phase
PHASE1
Status
Active Not Recruiting

Conditions

  • Primary Central Nervous System Lymphoma

Eligibility Criteria

Sex
ALL
Age
18 Years - 120 Years
Healthy Volunteers
Not accepted

Interventions

  • Isavuconazole — DRUG
    Isavuconazole to begin at least 3 days prior to ibrutinib and continue throughout chemotherapy (cycles 1-6)
  • TEDDI — DRUG
    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)
  • Rituximab — BIOLOGICAL
    Rituximab (R) given with TEDD and TEDDI every 3 weeks for cycles 1-6 (all arms)
  • Cytarabine — DRUG
    Cytarabine given via Ommaya reservoir (IT therapy) on days 1 and day 5 of cycles 2-6 (all arms)
  • TEDD — DRUG
    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)
  • Methotrexate — DRUG
    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 Details

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. 1. 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. 2. 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.

Key Dates

Start date
Aug 14, 2014
Status verified
Apr 2026
Primary completion
Sep 1, 2026
Completion
Dec 1, 2027

Study Design

Enrollment
68 participants (actual)
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm 1-A (original study design - prior to Amendment G)
    TEDD-R (cycle 1) with ibrutinib; TEDDI-R with cytarabine (cycles 2-6)
  • Experimental: Arm 1-B (original study design-prior to Amendment G)
    TEDDI-R with cytarabine
  • Experimental: Arm 2 (Dose Escalation; prior to Amendment 06/04/2021)
    TEDDI-R with cytarabine, and isavuconazole
  • Experimental: Arm 3 (Dose Expansion; prior to Amendment 06/04/2021)
    TEDDI-R with cytarabine and isavuconazole
  • Experimental: Arm 4 (Dose Expansion; Amendment 06/04/21)
    TEDDI-R, cytarabine or methotrexate, isavuconazole, ibrutinib for 10 days

Primary Outcome Measure

safety and feasibility in untreated PCNSL patients [ Time Frame: Initiation of ibrutinib until 30 days after treatment ]

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892-

Find similar trials in Bethesda, MD

By research site
National Institutes of Health Clinical Center· Bethesda, MD

Related Studies