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ALRN-6924 in Patients With Advanced Solid Tumors or Lymphomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02264613
Recruitment Status : Completed
First Posted : October 15, 2014
Last Update Posted : July 14, 2020
Sponsor:
Information provided by (Responsible Party):
Aileron Therapeutics, Inc.

Study Description
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Brief Summary:
This study evaluates the anti-tumor effects of ALRN-6924 in patients with advanced solid tumors or lymphomas with WT TP53.

Condition or disease Intervention/treatment Phase
Solid Tumor Lymphoma Peripheral T-Cell Lymphoma Drug: ALRN-6924 Phase 1 Phase 2

Detailed Description:

Open label, multi center, Phase 1 (dose escalation) and Phase 2a (dose expansion) study design to evaluate safety, tolerability, PK, PD and anti-tumor effects of ALRN-6924, alone or in combination with palbociclib, in patients with advanced solid tumors or lymphomas with wild-type (WT) TP53. ALRN-6924 is a stabilized cell-permeating peptide designed to disrupt the interaction between the p53 tumor suppressor protein and its predominant endogenous inhibitors, murine double minute 2 (MDM2) and murine double minute X (MDMX).

The Phase 1 portion of the study will enroll adults with histologically or cytologically confirmed malignancies that are metastatic or unresectable and for which standard treatment(s) are not available or are no longer effective. The Phase 2a portion of the study consists of separate cohorts that will enroll distinct groups of patients with specific solid tumors and/or lymphomas to further investigate the clinical safety profile and potential efficacy of ALRN-6924 alone or in a combination regimen.

Treatment will continue until unacceptable toxicity, patient or physician decision to discontinue therapy or disease progression that is either symptomatic, rapidly progressive, requires urgent intervention or is associated with a decline in performance status.

Patients with PTCL have been selected as a group to be further studied in Phase 2a.

Patients with MDM2-amplified or MDM2/CDK4-co-amplified solid tumors have been selected as another group to be further studied in Phase 2a.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 149 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2a Open-Label Study to Determine the Safety and Tolerability of ALRN-6924 Alone or in Combination in Patients With Advanced Solid Tumors or Lymphomas Expressing Wild-Type p53 Protein
Actual Study Start Date : October 2014
Actual Primary Completion Date : March 2020
Actual Study Completion Date : April 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Dose Regimen A (DR-A)
Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle.
 Drug: ALRN-6924
ALRN-6924 will be administered as an IV infusion
Experimental: Dose Regimen B (DR-B)
Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 4, 8 and 11 of a 21-day cycle
 Drug: ALRN-6924
ALRN-6924 will be administered as an IV infusion
Experimental: Dose Regimen C (DR-C)
Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 3 and 5 of a 21-day cycle
 Drug: ALRN-6924
ALRN-6924 will be administered as an IV infusion
Experimental: Combination with palbociclib
Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle Drug: Palbociclib Fixed-dose capsule administered orally on days 1 through 21 of a 28-day cycle
 Drug: ALRN-6924
ALRN-6924 will be administered as an IV infusion


Outcome Measures
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Primary Outcome Measures :
  1. Evaluate the safety and tolerability of ALRN-6924 in adult patients with advanced solid tumors or lymphomas with wild-type (WT) TP53 who are refractory to or intolerant of standard therapy, or for whom no standard therapy exists - Phase 1 [ Time Frame: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days) ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0

  2. Evaluate the safety and tolerability of ALRN-6924 in adult patients with advanced solid tumors or lymphomas with wild-type (WT) TP53 who are refractory to or intolerant of standard therapy, or for whom no standard therapy exists - Phase 2 [ Time Frame: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days) ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0

  3. Determine the maximum tolerated dose (MTD) - Phase 1 [ Time Frame: From the first dose until the end of the first cycle (each cycle is 28 days) ]
    Determine the dose limiting toxicities (DLT) and the maximum tolerated dose (MTD) or the optimal biological dose (OBD) of ALRN-6924 in adult patients with advanced solid tumors or lymphomas

  4. Determine Overall Response Rate - Phase 2 [ Time Frame: From the first dose until the first documented date of progression or date of death from any cause, whichever comes first, assessed up to 100 months ]
    The proportion of efficacy-evaluable patients who achieve complete response (CR) or partial response (PR), per investigator assessment, in accordance with RECIST 1.1 or iRECIST (for solid tumor patients) or Response Assessment in Neuro-Oncology (RANO) criteria (for glioblastoma patients).


Secondary Outcome Measures :
  1. Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas [ Time Frame: 8 weeks ]
    Peak Plasma Concentration (Cmax)

  2. Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas [ Time Frame: 8 weeks ]
    Area under the plasma concentration versus time curve (AUC)

  3. Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas [ Time Frame: 8 weeks ]
    Time of Peak Plasma Concentration (Tmax)

  4. Assess additional measures of anti-tumor activity, including duration of response, progression free survival, overall survival and time to response [ Time Frame: From the first dose until the first documented date of progression or date of death from any cause, whichever comes first, assessed up to 100 months ]
    The proportion of efficacy-evaluable patients who achieve complete response (CR) or partial response (PR), per investigator assessment, in accordance with RECIST 1.1 or iRECIST (for solid tumor patients) or Response Assessment in Neuro-Oncology (RANO) criteria (for glioblastoma patients).

  5. Assess additional pharmacologic properties, including biomarkers and immunogenicity [ Time Frame: Up to 24 weeks ]
    The correlation of response with MDM2, MDMX, and/or CDK4 gene copy number and other genetic and protein biomarkers


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Histologically or cytologically confirmed solid tumor or lymphoma that is not amenable to standard therapies.
  • Cohort specific biomarkers, including confirmed or anticipated WT TP53 (Phase 1 and PTCL expansion cohorts) and MDM2-amplification or MDM2/CDK4-co-amplification (solid tumor expansion cohort)
  • At least one target lesion that is measurable by RECIST 1.1, RANO or IWG 2014, as appropriate for tumor type
  • ECOG (Eastern Cooperative Oncology Group) performance status 0-1
  • Adequate coagulation and hematologic function
  • Adequate hepatic and renal function
  • Sufficient wash out from prior therapies and recovery from all significant acute toxicities

Key Exclusion Criteria

  • Prior treatment with an MDM2 inhibitor, with protocol specified exceptions
  • Known hypersensitivity to any study drug component
  • Protocol specified cardiovascular risk factors
  • Clinically significant gastrointestinal bleeding within 6 months
  • Clinically significant third-space fluid accumulation
  • Active uncontrolled infection, including HIV/AIDS or Hepatitis B or C
  • HPV positive tumors
  • Second malignancy within two years, with protocol specified exceptions
  • Pregnancy or lactation
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02264613


Locations
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United States, Alabama
Birmingham, Alabama, United States, 35294
United States, California
Duarte, California, United States, 91010
United States, Colorado
Denver, Colorado, United States, 80218
United States, Florida
Sarasota, Florida, United States, 34232
Tampa, Florida, United States, 33612
United States, Massachusetts
Boston, Massachusetts, United States, 02114
Boston, Massachusetts, United States, 02215
United States, New York
Bronx, New York, United States, 10461
New York, New York, United States, 10065
United States, South Carolina
Greenville, South Carolina, United States, 29605
United States, Tennessee
Nashville, Tennessee, United States, 37203
United States, Texas
Houston, Texas, United States, 77030
United States, Washington
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Aileron Therapeutics, Inc.
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Aileron Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02264613    
Other Study ID Numbers: ALRN-6924-1-01
First Posted: October 15, 2014    Key Record Dates
Last Update Posted: July 14, 2020
Last Verified: July 2020
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
 Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, T-Cell
Lymphoma, Non-Hodgkin