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ALRN-6924 in Patients With Advanced Solid Tumors or Lymphomas

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ClinicalTrials.gov Identifier: NCT02264613
Recruitment Status : Unknown
Verified June 2017 by Aileron Therapeutics.
Recruitment status was:  Recruiting
First Posted : October 15, 2014
Last Update Posted : June 27, 2017
Sponsor:
Information provided by (Responsible Party):
Aileron Therapeutics

Tracking Information
First Submitted Date  ICMJE October 7, 2014
First Posted Date  ICMJE October 15, 2014
Last Update Posted Date June 27, 2017
Actual Study Start Date  ICMJE October 2014
Estimated Primary Completion Date January 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 20, 2016)
  • Determine maximum tolerated dose (MTD) - DEP Phase [ Time Frame: From first dose up to 30 days after last dose ]
  • Determine Overall Response Rate - EXP Phase [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 10, 2014)
  • Thrombocytopenia [ Time Frame: 2 months ]
    Laboratory result, Grade 4 of any duration; Grade 3 >/= 3 days
  • Neutropenia [ Time Frame: 2 months ]
    Laboratory result, Grade 4 >/= 3 days; Grade 3, with fever
  • Dose-limiting toxicity [ Time Frame: 2 months ]
    Self report or clinical observation, Grade 3 or higher adverse event related to ALRN 6924
Change History Complete list of historical versions of study NCT02264613 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2016)
  • Pharmacokinetics of ALRN-6924: Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 2 months ]
  • Pharmacokinetics of ALRN-6924: Maximum plasma concentration (Cmax) [ Time Frame: 2 months ]
  • Pharmacokinetics of ALRN-6924: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] [ Time Frame: 2 months ]
  • Pharmacokinetics of ALRN-6924: Half-life (t1/2) [ Time Frame: 2 months ]
  • RECIST (Response Evaluation Criteria in Solid Tumors): primary tumor [ Time Frame: 2 months ]
    Imaging of primary solid tumor site
  • International Working Group response criteria: primary tumor (lymphoma patients) [ Time Frame: 2 months ]
    The International Working Group criteria is used to define and measure response in lymphoma patients
Original Secondary Outcome Measures  ICMJE
 (submitted: October 10, 2014)
  • Pharmacokinetics of ALRN-6924: Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 2 months ]
  • Pharmacokinetics of ALRN-6924: Maximum plasma concentration (Cmax) [ Time Frame: 2 months ]
  • Pharmacokinetics of ALRN-6924: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] [ Time Frame: 2 months ]
  • Pharmacokinetics of ALRN-6924: Half-life (t1/2) [ Time Frame: 2 months ]
  • RECIST (Response Evaluation Criteria in Solid Tumors): primary tumor [ Time Frame: 2 months ]
    Imaging of primary solid tumor site
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ALRN-6924 in Patients With Advanced Solid Tumors or Lymphomas
Official Title  ICMJE A Phase 1/2a Open-Label Study to Determine the Safety and Tolerability of ALRN-6924 in Patients With Advanced Solid Tumors or Lymphomas Expressing Wild-Type p53 Protein
Brief Summary This study evaluates the anti-tumor effects of ALRN-6924 in patients with advanced solid tumors or lymphomas with WT TP53.
Detailed Description

Open label, multi-center dose escalation (DEP) and dose expansion (EXP) study designed to evaluate safety, tolerability, PK (pharmacokinetics), PD (pharmacodynamics) and anti-tumor effects of ALRN-6924 in patients with advanced solid tumors or lymphomas with wild-type (WT) TP53. ALRN-6924 is a stapled peptide designed to disrupt integration between the p53 tumor suppression protein and inhibition by murine double minute 2 (MDM2) and murine double minute X (MDMX).

The DEP 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 can be enrolled.The EXP portion of the study 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 at the MTD or OBD. PTCL has been selected as one of the EXP groups to be further studied.

Treatment of patients in the DEP and EXP phases will continue in the study until documentation of disease progression, unacceptable toxicity, or patient or physician decision to discontinue study participation is made.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumor
  • Lymphoma
  • Peripheral T-Cell Lymphoma
Intervention  ICMJE Drug: ALRN-6924
ALRN-6924 will be administered as an IV infusion
Study Arms  ICMJE
  • Experimental: Dose Regimen A (DR-A)
    Fixed dose of ALRN-6924 per cohort, administered IV, Days 1, 8, and 15 every 28 days
    Intervention: Drug: ALRN-6924
  • Experimental: Dose Regimen B (DR-B)
    Fixed dose of ALRN-6924 per cohort, administered IV, Days 1, 4, 8 and 11 every 21 days
    Intervention: Drug: ALRN-6924
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: March 7, 2017)
130
Original Estimated Enrollment  ICMJE
 (submitted: October 10, 2014)
57
Estimated Study Completion Date  ICMJE July 2018
Estimated Primary Completion Date January 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Male or female patients age 18 years and older, inclusive, at the time of informed consent
  • Histologically- or cytologically-confirmed malignancy that is metastatic or unresectable and for which standard measures do not exist or are no longer effective (DEP) or a histologically confirmed diagnosis of PTCL based on pathology review at the local institution, using the most recent edition of the WHO Classification, relapsed or refractory disease after at least one prior systemic anticancer regimen (EXP in PTCL)
  • WT TP53 status
  • At least one target lesion that is measurable by RECIST 1.1 for solid tumors, or IWG 2014 for lymphoma
  • ECOG (Eastern Cooperative Oncology Group) performance status 0-1
  • Adequate hematologic function
  • Adequate hepatic function
  • Acceptable coagulation profile
  • Recovery from significant toxicities from previous therapies and sufficient time since last dose of previous therapy

Exclusion Criteria:

  • Previous treatment with investigational agents that inhibit MDM2 or MDMX activity (some MDM2-treated patients may be eligible)
  • Known hypersensitivity to any study drug component
  • Known and untreated brain metastases. Patients with primary CNS (central nervous system) malignancies are excluded.
  • History of coagulopathy, platelet disorder or history of non-drug induced thrombocytopenia
  • History of pulmonary embolism within 6 months prior to the first dose of ALRN-6924 or untreated DVT (deep vein thrombosis)
  • Required concurrent use of anti-coagulants or anti-platelet medication, with the exception of aspirin doses ≤81 mg/day, low-dose SC heparin or SC low-molecular-weight heparin for DVT prophylaxis, or heparin flushes to maintain IV catheter patency
  • Patients with pre-existing history of or known cardiovascular risk
  • Clinically significant gastrointestinal bleeding within 6 months prior to the first dose of ALRN-6924
  • Clinically significant third-space fluid accumulation
  • Active uncontrolled infection, including HIV/AIDS or Hepatitis B or C
  • Patients with cancers likely to be Human Papilloma Virus (HPV)-positive such as cervical cancers, oropharyngeal cancers or anal cancers must undergo additional screening to determine eligibility
  • Known history of another primary malignancy that has not been in remission for ≥2 years
  • Required use of medications predominantly cleared by hepatobiliary transporters within 48 hours of study drug infusion
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02264613
Other Study ID Numbers  ICMJE ALRN-6924-1-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Aileron Therapeutics
Study Sponsor  ICMJE Aileron Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Dawn Pinchasik, M.D. Aileron Therapeutics
PRS Account Aileron Therapeutics
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP