Phase 1 Study of the Dual MDM2/MDMX Inhibitor ALRN-6924 in Pediatric Cancer

Completed · Phase 1

Conditions studied: Leukemia, Brain Tumor, Solid Tumor, Lymphoma

In brief

This research study is studying a novel drug called ALRN-6924 as a possible treatment for resistant (refractory) solid tumor, brain tumor, lymphoma or leukemia. The drugs involved in this study are: * ALRN-6924 * Cytarabine (for patients with leukemia only)

Key facts

Study ID: NCT03654716
Run by: Dana-Farber Cancer Institute
People needed: 21
Starts: 2018-11-01
Expected to finish: 2023-07-17
Last updated by the study team: 2025-02-14

Who can join

Age: 1 and older, up to 21. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Age > 1 years and ≤ 21 years at time of enrollment.
Karnofsky performance status ≥ 50% for patients ≥16 years of age and/or Lansky ≥ 50% for patients <16 years of age
For Cohorts A and B
Participants must have evaluable or measurable disease.
Must have disease that is relapsed or refractory and for which standard curative or palliative measures do not exist or are no longer effective.
For Cohort A, participants must have histologically confirmed non-CNS primary solid tumors or lymphoma based upon biopsy or surgery at initial diagnosis and/or relapse/progression. The only exception to histologic confirmation is for patients with retinoblastoma.
For Cohort B, participants must have one of the following confirmed diagnoses:
Diagnosis of retinoblastoma
Histologic diagnosis of hepatoblastoma and WT TP53
Diagnosis of malignant rhabdoid tumor and WT TP53. For the purposes of this study, a diagnosis of malignant rhabdoid tumor will include histologic diagnosis (CNS atypical teratoid/rhabdoid tumor, rhabdoid tumor of the kidney or rhabdoid tumor of the soft tissue) AND molecular confirmation (loss of INI1 protein staining or BRG1 protein staining by IHC, or documentation of SMARCB1 or SMARCA4 mutation or loss)
Solid tumor, CNS tumor, or lymphoma with MDM2 amplification or high-copy gain and WT TP53
Solid tumor, CNS tumor, or lymphoma with MDMX amplification or high-copy gain and WT TP53
Solid tumor, CNS tumor, or lymphoma with PPM1D amplification, high-copy gain, or PPM1D activating mutation and WT TP53
Solid tumor or lymphoma with TET2 loss or loss-of-function mutation and WT TP53
Testing for MDM2, MDMX, TP53, SMARCB1, SMARCA4, PPM1D and TET2 variants must be performed in a laboratory certified to return results for clinical purposes in order to be used to qualify a patient for Cohort B.
For Cohort C
Participants must have a histologically confirmed diagnosis of relapsed or refractory AML, ALL, mixed lineage leukemia, biphenotypic leukemia, or other undifferentiated acute leukemia with one of these disease states:
Refractory disease defined as: Persistent disease after at least two induction cycles; OR
Relapsed disease defined as: Second or subsequent relapse, or any relapse that is refractory to salvage chemotherapy
Subjects in Cohort C must have ≥ 5% blasts (M2 or M3 marrow) definitively identified either on a bone marrow aspirate or biopsy sample, as assessed by morphology, immunohistochemical studies, flow cytometry, karyotype, cytogenetic testing such as fluorescent in situ hybridization (FISH) or other molecular studies.
Subjects must have CNS1 or CNS2 disease.
Absence of inactivating TP53 alteration by Next Generation Sequencing assay or PCR-based assay in a laboratory certified to return results for clinical purposes.
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy except organ function as noted below. Patients must meet the following minimum washout periods prior to enrollment:
Myelosuppressive chemotherapy: At least 14 days after the last dose of myelosuppressive chemotherapy (42 days for nitrosourea or mitomycin C).
Patients on Cohort C may have received any of the following medications without a "wash-out" period as long as other organ function requirements are met (methotrexate must not be given within 48 hours of ALRN-6924 planned start):

You may not qualify if…

Patients receiving medications within 48 hours of enrollment that are primarily cleared by organic anion transporter polypeptide [OATP] members OATP1B1 and OATP1B3
Pregnant participants will not be entered on this study given that the effects of ALRN-6924 on the developing human fetus are unknown.
Breastfeeding mothers are not eligible, because there is an unknown risk for adverse events in nursing infants secondary to treatment of the mother with ALRN-6924.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to ALRN-6924.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Patients with a known history of HIV, hepatitis B, and/or hepatitis C (testing not required as part of screening).
Patients with a known personal history of angioedema or known family history of hereditary angioedema.

Where it is running

UCSF Benioff Children's Hospital — San Francisco, California, United States
Dana-Farber Cancer Institute — Boston, Massachusetts, United States
Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
Texas Children's Hospital, Baylor College of Medicine — Houston, Texas, United States

Full record on ClinicalTrials.gov

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