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LeukemiaPhase 1NCT03654716

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

A Phase 1 study testing ALRN-6924 and Cytarabine in people with Leukemia and Brain Tumor, run by Dana-Farber Cancer Institute at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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) Read more about this study

Who is it for?
Ages 1 year to 21 years
Conditions the study is for
Leukemia, Brain Tumor, Solid Tumor
What is being tested?
ALRN-6924 and Cytarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
4 sitesUnited States
Study dates
1 Nov 2018to 17 Jul 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
Show all 63Show fewer
  • 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):
  • Standard maintenance therapy [any combination of vincristine, 6-mercaptopurine, corticosteroids, and/or low-dose methotrexate (45 mg/m2/week or less)]; Hydroxyurea; Patients on any cohort may have received intrathecal chemotherapy with methotrexate, hydrocortisone and/or cytarabine (non-liposomal) 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).
  • Radiotherapy:
  • At least 14 days after local XRT (small port, including cranial radiation);
  • At least 90 days must have elapsed after prior TBI, craniospinal XRT or if >50% radiation of pelvis;
  • At least 42 days must have elapsed if other substantial BM radiation;
  • At least 42 days must have passed since last MIBG or other radionuclide therapy.
  • Small molecule biologic therapy: At least 7 days following the last dose of a biologic agent. For agents with known adverse events occurring beyond 7 days, this duration must be extended beyond the time in which adverse events are known to occur. If extended duration is required, this should be discussed with and approved by the overall PI.
  • Monoclonal antibody: At least 21 days must have elapsed after the last dose of antibody.
  • Myeloid growth factors: At least 14 days following the last dose of long-acting growth factor (e.g. Neulasta) or 7 days following short-acting growth factor.
  • Autologous hematopoietic stem cell transplant and stem cell boost: Patients must be at least 60 days from day 0 of an autologous stem cell transplant or stem cell boost.
  • Allogeneic hematopoietic stem cell transplant or cellular therapies (including CAR-T cells): The patient must have no evidence of graft versus host diseaseand at least 90 days must have elapsed after allogeneic stem cell infusion. At least 42 days must have elapsed after last dose of other cellular therapy.
  • Solid Organ Transplantation: Patients with hepatoblastoma treated with liver transplantation will be eligible to enroll if they meet all of the following requirements:
  • At least 90 days must have elapsed from the date of liver transplant;
  • No clinical or radiographic evidence of rejection since the date of transplant; AND
  • All organ function requirements are met.
  • Major Surgery: At least 2 weeks from prior major surgical procedure. Note: Biopsy, CNS shunt placement/revision, and central line placement/removal are not considered major.
  • MDM2 inhibitors: Patients for Cohorts A and C may have received prior MDM2 inhibitor therapy. Patients in Cohort B must not have received prior MDM2 inhibitor therapy. Patients in all cohorts must not have received dual MDM2/MDMX inhibition.
  • Participants must have normal organ function as defined below.
  • Bone Marrow Function for Subjects in Cohorts A and B without Bone Marrow Involvement by Disease:
  • Absolute neutrophil count ≥1,000 /uL
  • Platelets ≥75,000 /uL and transfusion independent, defined as not receiving a platelet transfusion for at least 5 days prior to CBC documenting eligibility.
  • Hematologic Requirements for Subjects in Cohorts A and B with Bone Marrow Involvement by Disease:
  • Absolute neutrophil count ≥750 /uL
  • Platelets ≥50,000 /uL (may receive platelet transfusions)
  • Not known to be refractory to red cell and/or platelet transfusions.
  • Bone Marrow Function for Subjects in Cohorts C with Acute Leukemia
  • ---Not known to be refractory to red cell and/or platelet transfusions
  • Hepatic Function:
  • Total bilirubin ≤ 1.5 x upper limit of normal for age except for patients with known Gilbert syndrome who may enroll using direct bilirubin ≤ 1.5 x upper limit of normal for age as bilirubin criterion
  • ALT (SGPT) ≤ 3 x upper limit of normal (135 U/L). For the purpose of this study, the ULN for ALT is 45 U/L. Patients with acute leukemia AND leukemic infiltration of the liver may enroll to Cohort C if ALT < grade 2 and total bilirubin meets above requirement.
  • Serum albumin > 2 g/dL
  • Renal Function:
  • A serum creatinine within protocol limits based on age/sex. OR
  • Creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels greater than the above age/sex maximum allowed values.
  • Adequate Cardiac Function: QTc < 480 msec
  • For patients with CNS tumors (primary or metastatic), any baseline neurologic deficits (including seizure) must be stable for at least one week prior to study enrollment. Patients with CNS tumors receiving corticosteroids must be on a stable or decreasing dose at time of study entry.
  • Ability to understand and/or the willingness of the patient (or parent or legally authorized representative, if minor) to provide informed consent, using an institutionally approved informed consent procedure.
  • Participants of child-bearing or child-fathering potential must agree to use adequate contraception (hormonal birth control; intrauterine device; double barrier method; or total abstinence) throughout their participation, including up until 30 days after last dose of ALRN-6924.

Who cannot join

  • 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.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Texas Children's Hospital, Baylor College of Medicine

    Houston, Texas, 77030

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • UCSF Benioff Children's Hospital

    San Francisco, California, 94158

Other trials in United States

About this study

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)
Read the detailed description

This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.

In this research study, the investigators are evaluating a new drug, ALRN-6924, as a potential new treatment for children with cancer.

The FDA (the U.S. Food and Drug Administration) has not approved ALRN-6924 as a treatment for any disease.

This is the first time that ALRN-6924 will be studied in children.

ALRN-6924 is a drug that blocks certain proteins in tumor cells called MDM2 and MDMX. These proteins may be important in the growth of some cancers. Laboratory experiments and results from studies with adults show that ALRN-6924 may stop tumor growth and, in some cases, may cause tumor cells to die. ALRN-6924 has been tested in adults with cancer to find out about side effects and dosing in adults.

The purposes of this study are:

  • to evaluate side effects of ALRN-6924 and to find the best dose of ALRN-6924 when used in children.
  • to determine whether this drug may have benefits against the types of cancer seen in children
  • to see how the body breaks down ALRN-6924 by measuring the amount of ALRN-6924 in the blood.

One part of the study is for children with solid tumors, lymphoma, and brain tumors (Cohorts A or B). Another part of this study is for children with leukemia (Cohort C).

Being tested
ALRN-6924, Cytarabine
Keywords
Leukemia, Solid Tumor, Brain Tumor, Lymphoma, TP53, p53, MDM2, MDMX, PPM1D
Medical subject headings
Leukemia, Brain Neoplasms, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ALRN-6924Drug

    ALRN-6924 is a drug that blocks certain proteins in tumor cells called MDM2 and MDMX. These proteins may be important in the growth of some cancers. Laboratory experiments and results from studies with adults show that ALRN-6924 may stop tumor growth and, in some cases, may cause tumor cells to die.

  • CytarabineDrug

    Also called Cytosar

    Cytarabine belongs to the category of chemotherapy called antimetabolites. Antimetabolites are very similar to normal substances within the cell. When the cells incorporate these substances into the cellular metabolism, they are unable to divide

Study groups in NCT03654716
Study groupRoleWhat they receive
ALRN-6924 -- Cohort AExperimental* Participants will receive ALRN-6924 monotherapy on days 1, 4 (± 1 day), 8 (± 1 day), and 11 (± 1 day) of a 21-day cycle. * ALRN-6924 will be administered intravenously. * Participants with otherwise unselected TP53 wild type solid tumors and lymphoma will participate in this cohort.
Receives: Drug: ALRN-6924
ALRN-6924 -- Cohort BExperimental* Participants will receive ALRN-6924 monotherapy on days 1, 4 (± 1 day), 8 (± 1 day), and 11 (± 1 day) of a 21-day cycle. * ALRN-6924 will be administered intravenously. * Participants with solid and CNS tumors and lymphoma with specific diagnoses or molecular features will participate in this cohort.
Receives: Drug: ALRN-6924
ALRN-6924 -- Cohort CExperimental* Patients will receive ALRN-6924 in combination with cytarabine on days 1, 8 (± 1 day), and 15 (± 1 day) of a 28-day cycle. * Cytarabine is administered intravenously. * ALRN-6924 will be administered intravenously. * Participants with TP53 wild type acute leukemia will participate in this cohort.
Receives: Drug: ALRN-6924; Drug: Cytarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of patients with dose limiting toxicity by CTCAE v.5.0 for each dose level

    Measured: 2 years

  2. Percentage of patients with toxicity by CTCAE v.5.0

    Measured: 2 Years

Secondary outcomes (3)

  1. Peak plasma concentration of ALRN-6924

    Measured: 2 years

  2. Area under the curve (AUC) of ALRN-6924

    Measured: 2 years

  3. Objective response rate

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2018
  2. Study start1 Nov 2018
  3. Primary completion17 Jul 2023
  4. Study completion17 Jul 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03654716
Sponsor's protocol ID
18-284
Status last verified
Feb 2025
First submitted
29 Aug 2018
Last updated
14 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Berglund H, Salomonsson SL, Mohajershojai T, Gago FJF, Lane DP, Nestor M. p53 stabilisation potentiates [177Lu]Lu-DOTATATE treatment in neuroblastoma xenografts. Eur J Nucl Med Mol Imaging. 2024 Feb;51(3):768-778. doi: 10.1007/s00259-023-06462-3. Epub 2023 Oct 12.

    PubMed 37823909

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ALRN-6924 and Cytarabine in people with Leukemia and Brain Tumor, run by Dana-Farber Cancer Institute at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 63 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of patients with dose limiting toxicity by CTCAE v.5.0 for each dose level (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03654716, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2025.

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