A Randomized, Open-label, Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Patients With Relapsed or Refractory Mature B-cell non-Hodgkin Lymphoma.

A Randomized, Open-label, Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Patients With Relapsed or Refractory Mature B-cell non-Hodgkin Lymphoma. - 54179060LYM3003/Sparkle

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON50711

Enrollment

Registered

2016-05-23

Start date

2020-02-17

Completion date

Unknown

Last updated

2025-09-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

B-AL) Burkitt leukemia (ie Burkitt-like lymphoma (BLL) DLBCL Relapsed/refractory BL

Interventions

An Independent Data Monitoring Committee (IDMC) will be commissioned for this study. The IDMC will review the safety and efficacy data during the study and make recommendations as to the further con

Eligibility

Age

2 Years to 99 Years

Inclusion criteria

Inclusion criteria: - 1 to 1 cm in the longest diameter and >1 cm in the shortest diameter by radiological imaging b) bone marrow involvement c) cerebrospinal fluid with blasts present - Lansky-Karnofsky score of *50 - Adequate organ function - Must have recovered from the acute toxic effects of prior chemotherapy, immunotherapy, or radiotherapy, in the opinion of the investigator, prior to entering this study. - signed, written, informed consent or assent as applicaple. - Adolescents/young women of childbearing potential must be practicing a highly effective method of contraception (failure rate of

Exclusion criteria

Exclusion criteria: - Ongoing anticoagulation treatment with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon), or ongoing treatment with agents known to be strong CYP3A4/5 inhibitors, or has taken any disallowed therapies, Prohibited Medications, before the planned first dose of study drug - Inherited or acquired bleeding disorders - Clinically significant arrhythmias, complex congenital heart disease, or left ventricular ejection fraction (LVEF)

Design outcomes

Primary

Measure	Time frame
Run-in Part (Part 1): * Exposure (area under the plasma concentration-time curve [AUC]) * Apparent (oral) plasma clearance (CL/F), apparent (oral) volume of distribution (Vd/F), and derived measures of exposure such as maximum observed plasma concentration (Cmax) * Relationship between pharmacokinetic parameters and age or measure of body size Randomized Part (Part 2): * Difference in EFS between the 2 treatment groups (an event is defined as the time from randomization to death, disease progression, or lack of CR or PR after 3 cycles of treatment based on blinded independent event review)	—

Measure

Time frame

Run-in Part (Part 1): * Exposure (area under the plasma concentration-time curve [AUC]) * Apparent (oral) plasma clearance (CL/F), apparent (oral) volume of distribution (Vd/F), and derived measures of exposure such as maximum observed plasma concentration (Cmax) * Relationship between pharmacokinetic parameters and age or measure of body size Randomized Part (Part 2): * Difference in EFS between the 2 treatment groups (an event is defined as the time from randomization to death, disease progression, or lack of CR or PR after 3 cycles of treatment based on blinded independent event review)

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Secondary

Measure	Time frame
Run-in Part (Part 1): * Safety parameters, including gastrointestinal effects, immune function, intensified cardiac monitoring (in particular, after previous anthracycline exposure) * Overall response (complete response [CR], including CR biopsy-negative [CRb] and unconfirmed CR [CRu]) and partial response [PR]) * Phosphor BTK, as well as SYK, STAT3, caspase-3, BCL-xL, and cIAP1 expression at baseline and during treatment * B-cell receptor (BCR)/CD79B, CARD11, and MYD mutations * c-MYC, immunoglobulin, and T-cell receptor gene rearrangements at baseline * BTK occupancy * Visual analog scale score for palatability Randomized Part (Part 2): * Safety parameters, including gastrointestinal effects, immune function, intensified cardiac monitoring (in particular, after previous anthracycline exposure) * The proportion of subjects who achieve CR, (including CRb and CRu) and PR * Percent decrease in the sum of the products of the lesion diameters at Day 14 * Number and proportion of subjects who proceed to stem cell transplantation * The time interval from the first dose of ibrutinib to the first documented response for those subjects who respond * Duration calculated from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (PD) or death * Proportion of subjects with EFS at 2 and 3 years * The duration from the date of randomization to the date of the subjects death Phospho-BTK, as well as SYK, STAT3, caspase-3, BCL-xL, and cIAP1 expression at baseline and during treatment * BCR/CD79B, CARD11, and MYD mutations * c-MYC, immunoglobulin, and T-cell receptor gene rearrangements at baseline * BTK occupancy * Population pharmacokinetic parameters and derived systemic exposure to ibrutinib such as AUC * Relationship between pharmacokinetic parameters and age or measure of body size * Visual analog scale score for palatability	—

Measure

Time frame

Run-in Part (Part 1): * Safety parameters, including gastrointestinal effects, immune function, intensified cardiac monitoring (in particular, after previous anthracycline exposure) * Overall response (complete response [CR], including CR biopsy-negative [CRb] and unconfirmed CR [CRu]) and partial response [PR]) * Phosphor BTK, as well as SYK, STAT3, caspase-3, BCL-xL, and cIAP1 expression at baseline and during treatment * B-cell receptor (BCR)/CD79B, CARD11, and MYD mutations * c-MYC, immunoglobulin, and T-cell receptor gene rearrangements at baseline * BTK occupancy * Visual analog scale score for palatability Randomized Part (Part 2): * Safety parameters, including gastrointestinal effects, immune function, intensified cardiac monitoring (in particular, after previous anthracycline exposure) * The proportion of subjects who achieve CR, (including CRb and CRu) and PR * Percent decrease in the sum of the products of the lesion diameters at Day 14 * Number and proportion of subjects who proceed to stem cell transplantation * The time interval from the first dose of ibrutinib to the first documented response for those subjects who respond * Duration calculated from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (PD) or death * Proportion of subjects with EFS at 2 and 3 years * The duration from the date of randomization to the date of the subject*s death * Phospho-BTK, as well as SYK, STAT3, caspase-3, BCL-xL, and cIAP1 expression at baseline and during treatment * BCR/CD79B, CARD11, and MYD mutations * c-MYC, immunoglobulin, and T-cell receptor gene rearrangements at baseline * BTK occupancy * Population pharmacokinetic parameters and derived systemic exposure to ibrutinib such as AUC * Relationship between pharmacokinetic parameters and age or measure of body size * Visual analog scale score for palatability

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Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)