Peripheral T-cell Lymphomas (PTCL)Phase 1/2NCT05105412
Lenalidomide and Gemcitabine in Relapsed or Refractory Peripheral T-cell Lymphomas
A Phase 1/2 study testing Lenalidomide and Gemcitabine (Dose level 11), Lenalidomide and Gemcitabine (Dose level 21) and Lenalidomide and Gemcitabine (Dose level 31) in people with Peripheral T-cell Lymphomas (PTCL), run by National Health Research Institutes, Taiwan at 5 sites in Taiwan.
Trial summary
This is a single country multi-center, open-label phase Ib/II single-arm study in relapsed or refractory PTCL patients. Patients will be treated with the combination of lenalidomide and gemcitabine until disease progression, intolerable toxicity, or patient withdrawal. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Peripheral T-cell Lymphomas (PTCL)
- What is being tested?
- Lenalidomide and Gemcitabine (Dose level 11), Lenalidomide and Gemcitabine (Dose level 21) and Lenalidomide and Gemcitabine (Dose level 31)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 5 sitesTaiwan
- Study dates
- 15 Jun 2022to 30 Mar 2024
- Phase
- Phase 1/2
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Adult patients (20 years of age) have the following three subtypes of PTCL:
- (1)Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), (2)Angioimmunoblastic lymphoma (AITL), or (3)Anaplastic large cell lymphoma (ALCL). If patients had CD30-positive systemic ALCL, they should receive brentuximab vedotin before enrollment 2. (1) In transplant-eligible patients: patients who have relapsed disease after autologous stem-cell transplantation (2) In transplant-ineligible patients: patients who have received at least first-line systemic chemotherapy treatment and have a stable disease, progressive disease, or relapsed disease.
- 3. Patients have an ECOG Scale of Performance Status score of 0-1. 4. Patients have at least one measurable lesion by CT with a size of > 1.5 cm in at least one axis.
- 5. Patients have adequate renal function: serum creatinine (Cr) ≤ 1.5 times the upper limit of normal range (ULN) and calculated creatinine clearance (Ccr) ≥ 40 mL/min.
- 6. Patients have adequate bone marrow function:
- Absolute neutrophil count (ANC) ≥ 1500/μL, Without growth factor support (filgrastim or lenograstim) for at least 14 days
- Platelet count ≥ 75 000/μL. Evaluated at least 7 days after last platelet transfusion
- Hemoglobin ≥ 8 g/dL. May receive transfusion 7. Patients have adequate hepatic function: serum alkaline phosphatase (ALP), alanine, or aspartate aminotransferase levels (ALT \& AST) ≤ 2.5 times the ULN and serum total bilirubin ≤ 1.5 times the ULN.
Who cannot join
- Patients have already been exposed to lenalidomide and gemcitabine.
- Patients have less than 100 days from previous autologous stem cells transplantation prior to first study drug dose.
- Patients have HIV infection.
- Patients have cerebral or meningeal disease including signs or symptoms of progressive multifocal leukoencephalopathy.
- Patients have symptomatic neurologic disease compromising normal activities of daily living or requiring medication.
- Patients have any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose.
Show all 22Show fewer
- Patients received prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy (eg, immunoglobulin replacement, other monoclonal antibody therapies) within 4 weeks of first study drug dose.
- Patients have known hypersensitivity to any excipient contained in the drug formulation of lenalidomide or gemcitabine.
- Patients have known positive hepatitis B surface antigen but not receive anti-hepatitis B drug, or known or suspected active hepatitis B and C infection.
- Patients have diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- Patients have any of the following cardiovascular conditions or values within 6 months before the first dose of study drug:
- A left-ventricular ejection fraction <50%.
- Myocardial infarction within 2 years of randomization.
- New York Heart Association (NYHA) Class III or IV heart failure
- Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- Patients with unstable medical or psychiatric conditions or a history of any other serious medical disease deemed inappropriate for inclusion in this study, as determined by the investigators.
- Women who are pregnant or breastfeeding or have a positive pregnancy test during screening or Day 1 before the first dose of study drug.
- Women of childbearing potential who do not use two effective contraceptive methods from the time of signing informed consent through 6 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 do not agree to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
- Patients with a life expectancy of <3 months, as determined by the investigators.
- Patients with, as judged by the investigators, other contraindications for lenalidomide and gemcitabine administration, such as concurrent usage of drugs that may have potentially severe drug-drug interactions.
- Patients who are unwilling or unable to give consent.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Taiwan5 sites
Chang-Gung Memorial Hospital, Kaohsiung
Kaohsiung City
National Cheng-Kung University Hospital
Tainan
National Taiwan University Hospital
Taipei, 100
National Taiwan University Cancer Center
Taipei
Taipei Veterans General Hospital
Taipei
About this study
Official title: A Single Arm，Phase Ib/II Study of the Combination of Lenalidomide and Gemcitabine in Relapsed or Refractory Peripheral T-cell Lymphomas (PTCL)
This is a single country multi-center, open-label phase Ib/II single-arm study in relapsed or refractory PTCL patients. Patients will be treated with the combination of lenalidomide and gemcitabine until disease progression, intolerable toxicity, or patient withdrawal.
Read the detailed description
There are 3000 newly diagnosed lymphoma patients in Taiwan, and T-cell neoplasms accounted for 17.4% of total lymphomas. Peripheral T-cell lymphomas (PTCL) are heterogeneous malignancies, and peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL) are the most common subtypes.
Patients with relapsed or refractory PTCL to 1st-line chemotherapy had dismal prognosis under conventional chemotherapy. Combination of gemcitabine with platinum chemotherapy may be effective regimens, because they provided objective response rate (ORR) of 70% in PTCL patients. Since most salvage chemotherapy regimens provided limited activity in PTCL, many new regimens were studied in PTCL. Except brentuximab vedotin provided high activity through targeting CD30 on ALCL, new regimens (including lenalidomide) provided ORR about 20% and PFS about 3 months in PTCL.
Lenalidomide is an immunomodulatory agent, and it reduces T-regulatory cells, activates CD8-positive T cells, and increases natural killer cell numbers and in activation status. Gemcitabine may augment immune responses in several ways: activating T cells, increasing the amount of dendritic cells, increasing the amounts of antigens loaded onto antigen-presenting cells, and down-regulating T-regulatory cells. We design this phase 2 study under the hypothesis of synergistic effect of anti-tumor immunity and efficacy to PTCL in combination with lenalidomide and gemcitabine. The dose of lenalidomide monotherapy to treat PTCL is 25 mg daily based on previous studies, and we also start this dose in our study initially. Lenalidomide in combination with gemcitabine in 1st-line treatment of patients with advanced pancreatic cancer were studied before. Patients could tolerate oral lenalidomide of 25 mg daily on days 1 to 21, and intravenous gemcitabine dose of 1000 mg/m2 on days 1, 8, and 15, of each 28-day cycle. Because our enrolled patients will receive previous-line chemotherapy and combination of lenalidomide and gemcitabine may exacerbate myelosuppression, we designed oral lenalidomide of 25 mg daily on days 1 to 14, and intravenous gemcitabine dose of 1000 mg/m2 on days 1 and 8, of each 21-day cycle. In order to monitor toxicities and adjust drug doses closely, we arrange phase Ib study to evaluate dose-limiting toxicities about combination of lenalidomide and gemcitabine. The schedules about dose delays and modifications were also designed in phase Ib and II studies.
- Conditions
- Peripheral T-cell Lymphomas (PTCL)
- Being tested
- Lenalidomide and Gemcitabine (Dose level 11), Lenalidomide and Gemcitabine (Dose level 21), Lenalidomide and Gemcitabine (Dose level 31), Lenalidomide and Gemcitabine (Dose level 41)
- Keywords
- peripheral T-cell lymphomas (PTCL)
- Medical subject headings
- Lymphoma, T-Cell, Peripheral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lenalidomide and Gemcitabine (Dose level 11)Drug
Also called Dose level 11
lenalidomide 25 mg/day D1-D14 and gemcitabine 1000 mg/m2 D1, D8
Lenalidomide and Gemcitabine (Dose level 21)Drug
Also called Dose level 21
lenalidomide 15 mg/day D1-D14 and gemcitabine 1000 mg/m2 D1, D8
Lenalidomide and Gemcitabine (Dose level 31)Drug
Also called Dose level 31
lenalidomide 10 mg/day D1-D14 and gemcitabine 1000 mg/m2 D1, D8
Lenalidomide and Gemcitabine (Dose level 41)Drug
Also called Dose level 41
lenalidomide 10 mg/day D1-D14 and gemcitabine 800 mg/m2 D1, D8
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide and Gemcitabine | Experimental | Lenalidomide and Gemcitabine Receives: Drug: Lenalidomide and Gemcitabine (Dose level 11); Drug: Lenalidomide and Gemcitabine (Dose level 21); Drug: Lenalidomide and Gemcitabine (Dose level 31); Drug: Lenalidomide and Gemcitabine (Dose level 41) |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT
To evaluate the dose-limited toxicity (DLT) of combination of lenalidomide and gemcitabine
Measured: 12 months
ORR
To evaluate the objective response rate of combination of lenalidomide and gemcitabine by Lugano classification
Measured: 24 months
Secondary outcomes (3)
PFS
To evaluate the progression free survival of combination of lenalidomide and gemcitabine by Lugano classification
Measured: 24months
OS
To evaluate the overall survival of combination of lenalidomide and gemcitabine by Lugano classification
Measured: 24months
Treatment-related adverse events
To evaluate the number of participants with treatment-related adverse events assessed by CTCAE v 5.0
Measured: 24months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2021
- Study start15 Jun 2022
- Primary completion30 Mar 2024
- Study completion30 Mar 2024
Why it stopped: The resolution of DSMB
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral T-cell Lymphomas (PTCL)Studies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Health Research Institutes, Taiwan
- Sponsor type
- University, hospital or other
- Collaborators
- National Taiwan University Hospital, Chang Gung Memorial Hospital, National Cheng-Kung University Hospital, China Medical University Hospital
- Responsible party
- Sponsor
- Investigators
- Tsang-Wu Liu, Study director, Taiwan Cooperative Oncology Group, NHRI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05105412
- Sponsor's protocol ID
- T1421
- Status last verified
- Jun 2024
- First submitted
- 7 Oct 2021
- Last updated
- 8 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm，Phase Ib/II Study of the Combination of Lenalidomide and Gemcitabine in Relapsed or Refractory Peripheral T-cell Lymphomas (PTCL)
- ClinicalTrials.gov ID
- NCT05105412
- Acronym / sponsor ID
- T1421
- Conditions
- Peripheral T-cell Lymphomas (PTCL)
- Keywords
- peripheral T-cell lymphomas (PTCL)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The resolution of DSMB
- Enrolment
- 12 participants (actual)
- Lead sponsor
- National Health Research Institutes, TaiwanUniversity, hospital or other
- Collaborators
- National Taiwan University Hospital, Chang Gung Memorial Hospital, National Cheng-Kung University Hospital, China Medical University Hospital
- Study start
- 15 Jun 2022 (actual)
- Primary completion
- 30 Mar 2024 (actual)
- Study completion
- 30 Mar 2024 (actual)
- First posted
- 3 Nov 2021 (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.
This is a single country multi-center, open-label phase Ib/II single-arm study in relapsed or refractory PTCL patients. Patients will be treated with the combination of lenalidomide and gemcitabine until disease progression, intolerable toxicity, or patient withdrawal.
Detailed description
There are 3000 newly diagnosed lymphoma patients in Taiwan, and T-cell neoplasms accounted for 17.4% of total lymphomas. Peripheral T-cell lymphomas (PTCL) are heterogeneous malignancies, and peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL) are the most common subtypes.
Patients with relapsed or refractory PTCL to 1st-line chemotherapy had dismal prognosis under conventional chemotherapy. Combination of gemcitabine with platinum chemotherapy may be effective regimens, because they provided objective response rate (ORR) of 70% in PTCL patients. Since most salvage chemotherapy regimens provided limited activity in PTCL, many new regimens were studied in PTCL. Except brentuximab vedotin provided high activity through targeting CD30 on ALCL, new regimens (including lenalidomide) provided ORR about 20% and PFS about 3 months in PTCL.
Lenalidomide is an immunomodulatory agent, and it reduces T-regulatory cells, activates CD8-positive T cells, and increases natural killer cell numbers and in activation status. Gemcitabine may augment immune responses in several ways: activating T cells, increasing the amount of dendritic cells, increasing the amounts of antigens loaded onto antigen-presenting cells, and down-regulating T-regulatory cells. We design this phase 2 study under the hypothesis of synergistic effect of anti-tumor immunity and efficacy to PTCL in combination with lenalidomide and gemcitabine. The dose of lenalidomide monotherapy to treat PTCL is 25 mg daily based on previous studies, and we also start this dose in our study initially. Lenalidomide in combination with gemcitabine in 1st-line treatment of patients with advanced pancreatic cancer were studied before. Patients could tolerate oral lenalidomide of 25 mg daily on days 1 to 21, and intravenous gemcitabine dose of 1000 mg/m2 on days 1, 8, and 15, of each 28-day cycle. Because our enrolled patients will receive previous-line chemotherapy and combination of lenalidomide and gemcitabine may exacerbate myelosuppression, we designed oral lenalidomide of 25 mg daily on days 1 to 14, and intravenous gemcitabine dose of 1000 mg/m2 on days 1 and 8, of each 21-day cycle. In order to monitor toxicities and adjust drug doses closely, we arrange phase Ib study to evaluate dose-limiting toxicities about combination of lenalidomide and gemcitabine. The schedules about dose delays and modifications were also designed in phase Ib and II studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide and Gemcitabine | Experimental | Drug: Lenalidomide and Gemcitabine (Dose level 11), Drug: Lenalidomide and Gemcitabine (Dose level 21), Drug: Lenalidomide and Gemcitabine (Dose level 31), Drug: Lenalidomide and Gemcitabine (Dose level 41)Lenalidomide and Gemcitabine |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- (1)Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), (2)Angioimmunoblastic lymphoma (AITL), or (3)Anaplastic large cell lymphoma (ALCL). If patients had CD30-positive systemic ALCL, they should receive brentuximab vedotin before enrollment 2. (1) In transplant-eligible patients: patients who have relapsed disease after autologous stem-cell transplantation (2) In transplant-ineligible patients: patients who have received at least first-line systemic chemotherapy treatment and have a stable disease, progressive disease, or relapsed disease.
- 3. Patients have an ECOG Scale of Performance Status score of 0-1. 4. Patients have at least one measurable lesion by CT with a size of > 1.5 cm in at least one axis.
- 5. Patients have adequate renal function: serum creatinine (Cr) ≤ 1.5 times the upper limit of normal range (ULN) and calculated creatinine clearance (Ccr) ≥ 40 mL/min.
- Absolute neutrophil count (ANC) ≥ 1500/μL, Without growth factor support (filgrastim or lenograstim) for at least 14 days
- Platelet count ≥ 75 000/μL. Evaluated at least 7 days after last platelet transfusion
Key exclusion criteria (22 listed)
- Patients have already been exposed to lenalidomide and gemcitabine.
- Patients have less than 100 days from previous autologous stem cells transplantation prior to first study drug dose.
- Patients have HIV infection.
- Patients have cerebral or meningeal disease including signs or symptoms of progressive multifocal leukoencephalopathy.
- Patients have symptomatic neurologic disease compromising normal activities of daily living or requiring medication.
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 |
|---|---|---|
| Lenalidomide and Gemcitabine (Dose level 11)Also: Dose level 11lenalidomide 25 mg/day D1-D14 and gemcitabine 1000 mg/m2 D1, D8 | Drug | Lenalidomide and Gemcitabine |
| Lenalidomide and Gemcitabine (Dose level 21)Also: Dose level 21lenalidomide 15 mg/day D1-D14 and gemcitabine 1000 mg/m2 D1, D8 | Drug | Lenalidomide and Gemcitabine |
| Lenalidomide and Gemcitabine (Dose level 31)Also: Dose level 31lenalidomide 10 mg/day D1-D14 and gemcitabine 1000 mg/m2 D1, D8 | Drug | Lenalidomide and Gemcitabine |
| Lenalidomide and Gemcitabine (Dose level 41)Also: Dose level 41lenalidomide 10 mg/day D1-D14 and gemcitabine 800 mg/m2 D1, D8 | Drug | Lenalidomide and Gemcitabine |
Primary outcome
DLT
Time frame: 12 months
To evaluate the dose-limited toxicity (DLT) of combination of lenalidomide and gemcitabine
ORR
Time frame: 24 months
To evaluate the objective response rate of combination of lenalidomide and gemcitabine by Lugano classification
3 secondary outcomes
PFS
Time frame: 24months
OS
Time frame: 24months
Treatment-related adverse events
Time frame: 24months
Results and safety
The study was stopped early (reason given: The resolution of DSMB). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2024.
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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.
Tsang-Wu Liu study director
Taiwan Cooperative Oncology Group, NHRI
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lenalidomide and Gemcitabine (Dose level 11), Lenalidomide and Gemcitabine (Dose level 21) and Lenalidomide and Gemcitabine (Dose level 31) in people with Peripheral T-cell Lymphomas (PTCL), run by National Health Research Institutes, Taiwan at 5 sites in Taiwan.
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 8 inclusion and 22 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: stopped early, as of the sponsor's last update on 8 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Taiwan. 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 combined 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.
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 stopped early (reason given: The resolution of DSMB). Results are not available in the source record.
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?
DLT (time frame: 12 months). 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?
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 8 Jul 2024.