The main aims of this 2-part study are: * Phase I: To determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of IDP-121 in patients with multiple myeloma (MM), diffuse large B cell lymphoma not otherwise specified (DLBCL-NOS), high-grade B cell lymphoma with double or triple hit rearrangement (HGBL-DH/TH) and HGBL-NOS, and chronic lymphocytic leukemia (CLL). * Phase II: To evaluate the overall response rate (ORR), duration of response (DoR), time to progression (TTP), progression-free survival (PFS), event-free survival (EFS) and Overall survival (OS), in patients with MM, DLBCL-NOS, HGBL-DH/TH, HGBL-NOS or CLL treated with IDP-121 at the recommended Phase 2 Dose (RP2D).
This study is an open-label, multicenter, Phase 1/2 study with a Dose-Escalation phase (Phase 1) and an Expansion phase (Phase 2). Dose-Escalation (Phase 1): The dose-escalation phase will follow a classical 3+3 design but the first patient (sentinel) will be treated at dose level 1 (0.015 mg/kg) for one cycle, and, if no Dose-Limiting Toxicities (DLTs) occur, at dose level 2 (0.032 mg/kg) from cycle 2 onwards. Once the patient 1 (sentinel) is allowed to enter dose level 2, two additional patients will be enrolled to complete the cohort at dose level 2, and the dose-escalation phase will continue the 3+3 design. DLTs will be assessed based on the safety observed in cycle 1 (28 days) for all patients except for patient 1 (sentinel) where DLT will be assessed on safety observed in cycle 1 (at dose level 1) and cycle 2 (at dose level 2). For the first trial patient (sentinel) a single cycle will be completed (28 days) at dose level 0.015 mg/kg. Doses will not be escalated before all patients entered at the current dose level have been treated and observed for at least one complete cycle (28 days) at the intended dose- cohort IDP-121 dose and the number of DLTs among those patients in their first cycle has been determined. Before each escalation, Clinical Investigators will be consulted as part of a cohort review meeting to review and discuss all data (including safety, PK, PD and efficacy data) and agree on a dose-escalation, as appropriate. During the study, the Sponsor and Investigators may request that cohorts be enlarged or that intermediate doses between 2 planned escalation steps be explored based on all data existing at that time, including emerging safety and efficacy data and determinations of PK and PD. Also, the study will allow for alternative IDP-121 doses and/or schedules to be evaluated based on emerging data e.g., once a week dosing of IDP-121 (instead of twice a week). Data from all patients at all dose levels will be used to guide further dose-escalation or/and the MTD/RP2D. Expansion-Phase (Phase 2): Additional 17 patients will be enrolled for treatment at the RP2D level to further study safety and evaluate efficacy. Patients will receive 28-day cycles up to a maximum of 12 cycles of treatment or until any IDP-121 treatment discontinuation criteria are met (disease progression, unacceptable toxicity, etc). Patients in the Expansion- Phase may include one or more tumor types from those evaluated in dose-escalation.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
37
IDP-121 is a new chemical entity specifically designed to directly target cMyc protein that has demonstrated activity in multiple liquid and solid tumor cell lines and preclinical animal models
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, Spain
RECRUITINGHospital Universitario de Salamanca
Salamanca, Castille and León, Spain
RECRUITINGHospital Universitari Vall d'hebron
Barcelona, Spain
RECRUITINGHospital Durán i Reynals - ICO L´Hospitalet
Barcelona, Spain
RECRUITINGHospital Universitario 12 de Octubre
Madrid, Spain
RECRUITINGHospital Universitario La Paz
Madrid, Spain
RECRUITINGHospital Universitario Puerta de Hierro
Madrid, Spain
RECRUITINGHospital Clínico Universitario Virgen de la Arrixaca
Murcia, Spain
RECRUITINGHospital Universitario Virgen del Rocio
Seville, Spain
RECRUITINGHospital de Clinico Universitario de Valencia
Valencia, Spain
RECRUITING...and 1 more locations
Phase 1: Dose Escalation
Maximum tolerated dose (MTD)
Time frame: Through 1 treatment cycle (each cycle is 28 days)
Phase 1: Dose Escalation
Recommended phase 2 dose (RP2D)
Time frame: Through 12 treatment cycles (each cylce is 28 days) or until End of Treatment, whatever occurs first
Phase 2: Expansion Phase
Overall Response Rate (ORR)
Time frame: Based on iwCLL 20181, IMWG 20162, and the Lugano 20143 criteria for CLL, MM and Lymphomas, respectively; assessed at the end of study (12 months)
Phase 2: Expansion Phase
Duration of response (DoR)
Time frame: From disease response to disease progression, up to 12 months
Phase 2: Expansion Phase
Time to progression (TTP)
Time frame: From the first treatment day to day of the objective disease progression through study completion, an average of 12 months
Phase 2: Expansion Phase
Progression-free survival (PFS)
Time frame: From first treatment day to the first sign of disease progression or death from any cause assessed up to 12 months.
Phase 2: Expansion Phase
Event-free survival (EFS)
Time frame: From first treatment day to disease progression, death, or discontinuation of treatment from any cause through study completion, an average of 12 months
Phase 2: Expansion Phase
Overall survival (OS)
Time frame: From first treatment day to death from any cause, up to 12 months
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