Brigatinib in Relapsed or Refractory ALK-Positive Anaplastic Large Cell Lymphoma

NCT03719898 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: HM-11718-1032
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

FDA approved drugs to treat patients with relapsed or refractory anaplastic large cell lymphoma (ALCL) has a median progression free survival of 20 months. Majority of patients relapse in 2 years. This study will evaluate overall response rate of next generation ALK inhibitor brigatinib in ALK positive ALCL patients by overcoming mechanisms of resistance to ALK inhibitors on cancer patients.

Conditions

Anaplastic Large Cell Lymphoma, ALK-Positive

Outcome Measures

Primary Outcomes (1)

• objective response rate

  proportion of patients with tumor size reduction of a predefined amount and for a minimum time period measured using RECIL 2017 criteria

  2 years

Secondary Outcomes (4)

• To assess the incidence of adverse events as assessed by NCI CTCAE v5.0 for 2 years

  2 years

• To measure the overall survival (OS) at 1 and 2 years from treatment initiation

  5 years

• To measure progression-free survival (PFS) at 1 and 2 years from treatment initiation

  5 years

• To measure the duration of response (DOR) for the period of 2 years

  2 years

Other Outcomes (7)

• To evaluate the frequency of NPM/ALK quantitative polymerase chain reaction (qPCR) positivity in plasma

  2 years

• The evaluate the persistence of NPM/ALK DNA construct in plasma and correlation with rate of relapse

  2 years

• To evaluate for ALK mutations in tumor and plasma at baseline and at time of relapse

  2 years

Study Arms (1)

Brigatinib

EXPERIMENTAL

90 mg daily orally for 7 days, then 180 mg daily orally during first cycle; 180 daily orally thereafter during every subsequent cycle. Each cycle has 28 days

Drug: Brigatinib

Interventions

Brigatinib DRUG

Brigatininb is administered in tablet form. It is to be taken until disease progression, unacceptable toxicity or completion of 24 cycles. patients may continue to take brigatininb beyond 24 cycles if they are benefiting from the drug

Brigatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a histologically confirmed diagnosis of relapsed or refractory ALCL with documented ALK+ status
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIL 2017 criteria as described in detail in section 11.0
• Ongoing toxicities from prior therapy must be resolved to ≤ grade 1 (with the exceptions of grade 2 peripheral neuropathy and/or alopecia). Patients with existing toxicities that are non-significant even though greater than grade 1 can be enrolled after discussion with the sponsor-investigator.
• Age \> 18 years.
• ECOG performance status 0-2
• Prior use of ALK inhibitors aside from brigatinib is permitted but 8 patients enrolled need to be ALK inhibitor treatment naive
• Patients with no archival tissue available must be agreeable to fresh biopsy at baseline.
• Patients with a known history of HIV are permitted provided the CD4 count ≥ 100 cells/µL and serum HIV viral load \< 50 copies/mL. Patients must be on stable combination antiretroviral therapy at the time of treatment initiation.
• Patients must have normal organ and marrow function as defined below
• Absolute neutrophil count \> 1,000/mcL
• Platelets \> 75,000/mcL (or 50,000/mcL if known bone marrow involvement by lymphoma)
• Total bilirubin within normal institutional limits (up to 2x ULN if history of Gilbert's syndrome or known liver involvement)
• AST/ALT (SGOT/SGPT) \< 2 times institutional normal limits
• Creatinine within 1.5 x upper limit of normal institutional limits OR
• Creatinine clearance \> 30 ml/min/1.73 m2 for patients with creatinine levels above 1.5x upper institutional normal

You may not qualify if:

• History of another active primary malignancy within 2 years of initiating study treatment with the exception of non-melanomatous skin cancer, or any cancer that in the judgment of the investigator has been treated with curative intent and will not interfere with the study treatment plan and response assessment.
• Patients who have received chemotherapy or radiation therapy within 2 weeks of initiating study treatment.
• Patients may not be receiving any other investigational agents.
• Patients who have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening or asymptomatic disease requiring an increasing dose of corticosteroids to control symptoms within 7 days prior to randomization.
• Note: If a patient has worsening neurological symptoms or signs due to CNS metastasis, the patient needs to complete local therapy and be neurologically stable (with no requirement for an increasing dose of corticosteroids or use of anticonvulsants) for 7 days prior to enrollment.
• History of allergic reactions attributed to other ALK inhibitors
• History of interstitial pneumonitis or drug-related pneumonitis
• Impaired gastrointestinal function that may affect oral absorption of brigatinib
• Patients with known active Hepatitis B or Hepatitis C (defined as having a detectable hepatitis B or C viral load)
• 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. Physician's discretion may be exercised to determine eligibility for patients with psychiatric illness/social situations.
• Pregnant or breast-feeding. Refer to section 4.4 for further detail.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19011, United States

Location

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic

Interventions

brigatinib

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Refractory or relapsed ALK positive ALCL patients who may or my not have previously received treatment with any ALK inhibitor for any indication

Study Record Dates

• First Submitted: October 16, 2018
• First Posted: October 25, 2018
• Study Start: December 6, 2018
• Primary Completion: March 18, 2020
• Study Completion: June 16, 2020
• Last Updated: January 5, 2021

Record last verified: 2021-01

Locations

US (1)