Anaplastic Large Cell Lymphoma, ALK-PositivePhase 2NCT03719898
Brigatinib in Relapsed or Refractory ALK-Positive Anaplastic Large Cell Lymphoma
A Phase 2 study testing Brigatinib in people with Anaplastic Large Cell Lymphoma, ALK-Positive, run by Fox Chase Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anaplastic Large Cell Lymphoma, ALK-Positive
- What is being tested?
- Brigatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Dec 2018to 16 Jun 2020
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Serum lipase/amylase ≤1.5 × ULN
- Hemoglobin ≥10 g/dL (can be transfused to achieve Hgb ≥10 g/dL)
- Ability to understand and willingness to sign a written informed consent and HIPAA consent document. LARs are allowed to sign on patient's behalf with proper documentation.
- Female patients who are postmenopausal for at least 1 year before the screening visit, or are surgically sterile. Female patients of childbearing potential should agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
- Male patients, even if surgically sterilized (i.e., status post-vasectomy), who agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19011
About this study
Official title: A Phase II Study of Brigatinib in Relapsed or Refractory ALK-Positive Anaplastic Large Cell Lymphoma
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.
Read the detailed description
Although patients with ALK+ anaplastic large cell lymphoma (ALCL), a type of peripheral T-cell lymphoma (PTCL), are considered to have a favorable prognosis, relapse is not uncommon if multiple International Prognostic Index (IPI) risk factors, age ≥ 40, and beta-2 microglobulin ≥ 3 mg/L are present at diagnosis. For patients older than 40 years at diagnosis and beta-2 microglobulin ≥ 3 mg/L, progression-free survival (PFS) and overall survival (OS) is less than 50% at 2.5 years when treated with standard anthracycline-based induction therapy. Patients with ALK+ ALCL with 3 or more IPI risk factors have a 5-year PFS rate of only 20% to 30%. In total, approximately 40 to 65% of patients with ALCL develop recurrent disease after front-line chemotherapy and at relapse, the disease is historically resistant to conventional chemotherapy.
Current FDA approved for treatment of relapsed or refractory PTCLs have a median PFS of 20 months and majority of patients relapse within 2 years. Despite ALK tyrosine kinase being an attractive target for management of relapsed or refractory ALK+ ALCL, ALK gene rearrangement makes cancer resistant to first and 2nd generation ALK inhibitors. Brigatinib is a next generation inhibitor with broad activity aganst a broad spetrum of resistant ALK mutants. Brigatinib has been shown to overcome mechanisms associated with resistane to 1st and 2nd generation ALK inhibitors. It is approved as 2nd line of treament in non small cell lung cancer patients. and is being tested in patients with relapsed or refractory ALK-positive ALCL.
- Being tested
- Brigatinib
- Medical subject headings
- Lymphoma, Large-Cell, Anaplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrigatinibDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Brigatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years
Secondary outcomes (4)
To assess the incidence of adverse events as assessed by NCI CTCAE v5.0 for 2 years
Adverse events will be documented by NCI CTCAE v 5.0 criteria
Measured: 2 years
To measure the overall survival (OS) at 1 and 2 years from treatment initiation
Overall survival will be measured as the length of time patients survive from the day of treatment.
Measured: 5 years
To measure progression-free survival (PFS) at 1 and 2 years from treatment initiation
Progression free survival will be measured as the length of time from treatment to progression of disease as measured by radiologic evaluation
Measured: 5 years
To measure the duration of response (DOR) for the period of 2 years
DOR will be length of time from initial response to tumor progression documented by radiologic evaluation
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2018
- Study start6 Dec 2018
- Primary completion18 Mar 2020
- Study completion16 Jun 2020
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anaplastic Large Cell Lymphoma, ALK-PositiveStudies of the same condition, open and under way.
- More trials run by Fox Chase Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Refractory or relapsed ALK positive ALCL patients who may or my not have previously received treatment with any ALK inhibitor for any indication
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03719898
- Sponsor's protocol ID
- HM-117
- Other IDs
- 18-1032
- Status last verified
- Jan 2021
- First submitted
- 16 Oct 2018
- Last updated
- 5 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Brigatinib in Relapsed or Refractory ALK-Positive Anaplastic Large Cell Lymphoma
- ClinicalTrials.gov ID
- NCT03719898
- Acronym / sponsor ID
- HM-117
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Slow accrual
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Study start
- 6 Dec 2018 (actual)
- Primary completion
- 18 Mar 2020 (actual)
- Study completion
- 16 Jun 2020 (actual)
- First posted
- 25 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Although patients with ALK+ anaplastic large cell lymphoma (ALCL), a type of peripheral T-cell lymphoma (PTCL), are considered to have a favorable prognosis, relapse is not uncommon if multiple International Prognostic Index (IPI) risk factors, age ≥ 40, and beta-2 microglobulin ≥ 3 mg/L are present at diagnosis. For patients older than 40 years at diagnosis and beta-2 microglobulin ≥ 3 mg/L, progression-free survival (PFS) and overall survival (OS) is less than 50% at 2.5 years when treated with standard anthracycline-based induction therapy. Patients with ALK+ ALCL with 3 or more IPI risk factors have a 5-year PFS rate of only 20% to 30%. In total, approximately 40 to 65% of patients with ALCL develop recurrent disease after front-line chemotherapy and at relapse, the disease is historically resistant to conventional chemotherapy.
Current FDA approved for treatment of relapsed or refractory PTCLs have a median PFS of 20 months and majority of patients relapse within 2 years. Despite ALK tyrosine kinase being an attractive target for management of relapsed or refractory ALK+ ALCL, ALK gene rearrangement makes cancer resistant to first and 2nd generation ALK inhibitors. Brigatinib is a next generation inhibitor with broad activity aganst a broad spetrum of resistant ALK mutants. Brigatinib has been shown to overcome mechanisms associated with resistane to 1st and 2nd generation ALK inhibitors. It is approved as 2nd line of treament in non small cell lung cancer patients. and is being tested in patients with relapsed or refractory ALK-positive ALCL.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Refractory or relapsed ALK positive ALCL patients who may or my not have previously received treatment with any ALK inhibitor for any indication
| Arm | Type | Receives |
|---|---|---|
| Brigatinib | Experimental | Drug: Brigatinib90 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BrigatinibBrigatininb 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 | Drug | Brigatinib |
Primary outcome
objective response rate
Time frame: 2 years
proportion of patients with tumor size reduction of a predefined amount and for a minimum time period measured using RECIL 2017 criteria
4 secondary outcomes
To assess the incidence of adverse events as assessed by NCI CTCAE v5.0 for 2 years
Time frame: 2 years
To measure the overall survival (OS) at 1 and 2 years from treatment initiation
Time frame: 5 years
To measure progression-free survival (PFS) at 1 and 2 years from treatment initiation
Time frame: 5 years
To measure the duration of response (DOR) for the period of 2 years
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Brigatinib in people with Anaplastic Large Cell Lymphoma, ALK-Positive, run by Fox Chase Cancer Center at 1 site 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 20 inclusion and 11 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: withdrawn, as of the sponsor's last update on 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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?
objective response rate (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Jan 2021.