Trial Title:
A Phase 1/2 Study of IDP-121 in Patients With Relapsed/Refractory Hematologic Malignancies
NCT ID:
NCT05908409
Condition:
Multiple Myeloma (MM)
Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
Double Hit Lymphoma
High Grade B-Cell Lymphoma, Not Otherwise Specified
Chronic Lymphocytic Leukemia (CLL)
Triple Hit Lymphoma
Conditions: Official terms:
Lymphoma
Multiple Myeloma
Lymphoma, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large B-Cell, Diffuse
Hematologic Neoplasms
Neoplasms, Plasma Cell
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
IDP-121
Description:
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
Arm group label:
Dose Escalation: IDP-121 0.015 Up to 0.70 mg/kg
Arm group label:
Expansion Phase: IDP-121 at RP2D
Summary:
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).
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥18 years
2. Performance status (ECOG) < 2
3. Life expectancy ≥3 months
4. Patient is, in the investigator's opinion, willing and able to comply with the
protocol requirements.
5. Patient has given voluntary written informed consent before performance of any
study- related procedure not part of normal medical care, with the understanding
that consent may be withdrawn by the patient at any time without prejudice to their
future medical care.
6. Patients diagnosed with chronic lymphocytic leukemia (CLL), diffuse large B cell
lymphoma not otherwise specified (DLBCL-NOS), high-grade B cell lymphoma with double
or triple hit rearrangement (HGBL-DH/TH), HGBL-NOS and multiple myeloma (MM) who are
ineligible to receive the available treatments.
7. Adequate hematological or biochemical parameters as specified below
1. Hemoglobin > 8.0 g/dl (without transfusion support within 7 days)
2. Platelets count > 75 x109/L (without transfusional support within 7 days)
3. Absolute neutrophil count (ANC) > 0.75 x109/L (without G-CSF support within 7
days)
4. Aspartate transaminase (AST): <2.5 x the upper limit range (in patients with no
liver metastases or <5 x ULN in patients with liver metastases)
5. Alanine transaminase (ALT): < 2.5 x the upper limit range (in patients with no
liver metastases or <5 x ULN in patients with liver metastases)
6. Total bilirubin: < 2 x the upper limit range.
7. Calculated or measured creatinine clearance: > 50 mL/min (calculated from the
Cockcroft-Gault formula).
8. Left ventricular ejection fraction > 50% or above the Institutional Lower Limit of
Normal (LLN), whichever is lower .
Exclusion Criteria:
1. Persistent clinically significant non-hematological toxicity related to previous
treatments. The presence of alopecia and NCI-CTC grade <2 symptomatic peripheral
neuropathy is allowed.
2. Pregnant or lactating women; men and women of reproductive potential* (as defined in
the Appendix 2) who are not using effective contraceptive methods (combined hormonal
contraception associated with inhibition of ovulation; progestogen-only hormonal
contraception associated with inhibition of ovulation, intrauterine device,
intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised
partner, sexual abstinenence).
*A woman is considered of childbearing potential (WOCBP), i.e. fertile, following
menarche and until becoming post-menopausal unless permanently sterile. A man is
considered fertile after puberty unless permanently sterile by bilateral
orchidectomy
3. History of any other neoplastic disease in the last five years (except basal cell
carcinoma, skin epithelioma or carcinoma in situ of any site)
4. History of clinically significant hypotension.
5. History of clinically significant allergic or hyper-sensitivity reactions.
6. History or known clinically significant vascular disease or known high risk of
vascular disease (as assessed by the treating physician) including (but not limited
to):
- Thromboembolism
- Peripheralarterialdisease - Vasculitis
7. Other relevant diseases or adverse clinical conditions:
- Congestive heart failure or angina pectoris, myocardial infarction within 12
months before inclusion in the study.
- Uncontrolled arterial hypertension or cardiac arrhythmias (i.e., requiring a
change in medication within the last 3 months or hospital admission within the
past 6 months).
- Historyofsignificantneurologicalorpsychiatricdisorders
8. Clinically significant or active infection.
9. Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis)
10. The patient is known to be human immunodeficiency virus (HIV) positive, Hepatitis B
surface antigen-positive, active hepatitis C infection or CMV positive.
11. Concomitant anti-tumor therapy within 14 days prior to Day 1 of Cycle 1.
12. Prior allogeneic transplantation in the last 3 months or currently active GVHD with
immunossupresive treatment
13. Limitation of the patient's ability to comply with the treatment or follow-up
protocol.
14. If a COVID-19 vaccine is administered it should be done >72 hours prior to study
treatment initiation or after the completion of the dose-limiting toxicity (DLT)
period (if patient is participating in the dose-escalation phase").
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hospital Universitario Marques de Valdecilla
Address:
City:
Santander
Zip:
39008
Country:
Spain
Status:
Recruiting
Contact:
Phone:
+34942202573
Email:
ocioem@unican.es
Investigator:
Last name:
Enrique Ocio San Miguel
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario de Salamanca
Address:
City:
Salamanca
Zip:
37007
Country:
Spain
Status:
Recruiting
Contact:
Phone:
+34923291316
Email:
mvmateos@usal.es
Investigator:
Last name:
María Victoria Mateos Manteca
Email:
Principal Investigator
Facility:
Name:
Hospital Universitari Vall d'hebron
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Recruiting
Contact:
Phone:
+34934893806
Email:
fbosch@vhio.net
Investigator:
Last name:
Francesc Bosch Albareda
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Status:
Recruiting
Contact:
Phone:
+34917792877
Email:
jmartinezlo1967@gmail.com
Contact backup:
Email:
jmarti01@med.ucm.es
Investigator:
Last name:
Joaquín Martínez López
Email:
Principal Investigator
Facility:
Name:
Hospital Clínico Universitario Virgen de la Arrixaca
Address:
City:
Murcia
Zip:
30120
Country:
Spain
Status:
Recruiting
Contact:
Email:
valentin.cabanas@gmail.com
Investigator:
Last name:
Valentín Cabañas Perianes
Email:
Principal Investigator
Start date:
June 5, 2023
Completion date:
December 22, 2025
Lead sponsor:
Agency:
IDP Discovery Pharma S.L.
Agency class:
Industry
Source:
IDP Discovery Pharma S.L.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05908409
https://www.idp-pharma.com/
