Adult T-cell Leukemia/LymphomaPhase 1NCT04639843
Doxorubicin, CC-(486) (5-azacitidine), Romidepsin, and Duvelisib (hARD) for T-cell Lymphoma
A Phase 1 study testing CC-486 (5-azacitidine), Duvelisib and Romidepsin in people with Adult T-cell Leukemia/Lymphoma and Extranodal NK-/T-cell Lymphoma, Nasal Type, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: T-cell lymphomas (TCLs) are rare cancers. Many types of TCLs do not develop in the lymph nodes but in places like the skin, spleen, and bone marrow. Researchers want to see if a mix of 4 drugs can help people with TCL. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult T-cell Leukemia/Lymphoma, Extranodal NK-/T-cell Lymphoma, Nasal Type, Enteropathy-Associated T-Cell Lymphoma
- What is being tested?
- CC-486 (5-azacitidine), Duvelisib and Romidepsin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Nov 2022to 3 Nov 2022
- Phase
- Phase 1
- 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
None listed.
Who cannot join
- Patients who are receiving any other investigational agents.
- Patients in need of immediate cytoreduction.
- Chemotherapy or monoclonal antibody therapy within 4 weeks prior to start of treatment (6 weeks for nitrosoureas or mitomycin C); small molecule or radiation therapy within 2 weeks.
- Prior lifetime doxorubicin therapy >= 400 mg/m^2.
- Prior radiation therapy to chest with fields involving the heart.
- Major surgery within 4 weeks prior to start of treatment
Show all 33Show fewer
- History of tuberculosis treatment within the 2 years prior to start of treatment
- Administration of a live or live attenuated vaccine within 6 weeks prior to start of treatment, or of mRNA and adenovirus-based vaccines within 2 weeks prior to start of treatment
- Patients who have received all of the planned study drugs - i.e., duvelisib, romidepsin, and CC-486 (5-azacitidine) - at any time point during prior treatments for TCL. Patients who have received one or two of the three drugs (alone or in combination) remain eligible.
- Patients with previous malignant disease other than the target malignancy within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ.
- Systemic treatment for acute or chronic graft versus host disease (GVHD) within 12 weeks of the first dose of duvelisib
- Cohort 1 (Dose Escalation) only: history of grade 3/4 GVHD
- Patients with active acute or chronic GVHD
- History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function. Pulmonary function testing (PFTs) will be evaluated at screening.
- Prior history of drug-induced colitis or drug-induced pneumonitis.
- History of chronic liver disease or veno-occlusive disease
- History of allergic reactions or known or suspected hypersensitivity attributed to compounds of similar chemical or biologic composition to duvelisib, romidepsin or mannitol and CC-486 (5-azacitidine).
- Ongoing treatment with systemic steroids at a dose higher than 20 mg of prednisone (or equivalent) once daily
- Patients with uncontrolled intercurrent illness including, but not limited to, detectable CMV or EBV viral load, and ongoing or active bacterial, fungal, or viral infection requiring systemic therapy, with the following exceptions:
- Human immunodeficiency virus (HIV)-infected patients on effective anti- retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable and on suppressive therapy, if indicated.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- Subjects on antimicrobial, antifungal, or antiviral prophylaxis.
- History of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis), celiac disease (i.e., sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism or excretion of the study drugs and/or predispose the subject to an increased risk of gastrointestinal toxicity.
- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (>= New York Heart Association Classification Class II), congenital long QT syndrome, or other serious cardiac arrhythmia including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min).
- Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes.
- Uncontrolled hypertension, i.e., blood pressure (BP) of >=160/95 at screening; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria.
- Triplicate average baseline QTcF interval >= 480 ms during screening
- Patients taking drugs leading to significant QT prolongation Note: A 5 half-life washout period must have elapsed following the use of these drugs prior to administration of romidepsin.
- Concomitant use of rifampin and other strong CYP3A4 inhibitors and inducers within 2 weeks prior to start of treatment.
- Inability to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV).
- Other severe acute or chronic medical conditions including psychiatric conditions such as recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
- Pregnant or lactating women. NOTE: Pregnant women are excluded from this study because based on findings in animals and its mechanism of action, duvelisib can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of duvelisib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes including embryo-fetal mortality. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with duvelisib, breastfeeding should be discontinued if the mother is treated with duvelisib. These potential risks may also apply to other agents used in this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Phase 1 Study of Doxorubicin, CC-486 (5-azacitidine), Romidepsin, and Duvelisib (hARD) for T-cell Lymphoma
Background:
T-cell lymphomas (TCLs) are rare cancers. Many types of TCLs do not develop in the lymph nodes but in places like the skin, spleen, and bone marrow. Researchers want to see if a mix of 4 drugs can help people with TCL.
Read more
Objective:
To test if the combination of romidepsin, CC-486 (5-azacitidine), duvelisib, and doxorubicin can be used safely in people with TCL.
Eligibility:
Adults 18 and older with TCL that is newly diagnosed or that returned after or did not respond to standard treatments.
Design:
Participants will be screened on a separate protocol. They may have a tumor biopsy.
Participants will have medical histories, medicine reviews, and physical exams. Their ability to do daily activities will be assessed. They will have blood and urine tests.
Participants will take duvelisib and CC-486 (5-azacitidine) by mouth. They will get romidepsin and doxorubicin by intravenous infusion. They will take the drugs for up to eight 21-day cycles. They will keep a medicine diary.
Participants will have a bone marrow aspiration and/or biopsy. Bone marrow will be taken through a needle inserted in the hip.
Participants will have tumor imaging scans. Some may have a brain MRI and lumbar puncture. Some may have skin assessments.
Participants will give blood, saliva, and tumor samples for research.
Participants will have a safety visit 30 days after treatment ends. Then they will have follow-up visits every 60 days for 6 months, then every 90 days for 2 years, and then every 6 months for 2 years. Then they will have yearly visits until their disease gets worse or they start a new treatment....
Read the detailed description
Background:
T-cell lymphomas (TCLs) are a heterogeneous group of lymphoid malignancies defined by clonal proliferation of post-thymic T lymphocytes.
Patients with newly diagnosed TCLs are most commonly treated with a CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone)-like regimen, with less than 30% having durable complete responses (CRs). Of the chemotherapy agents used, doxorubicin is the one which was consistently associated with prolonged progression-free survival (PFS) and overall survival (OS) in retrospective studies.
Treatment options for the 70% of patients with TCL who relapse are limited and of minimal efficacy; novel treatment strategies are urgently needed.
Many TCL have mutations in epigenetic modifier genes, and histone deacetylase inhibitors such as romidepsin are approved for treatment of peripheral T-cell lymphoma (PTCL); however, the overall response rate (ORR) with single-agent treatment is only 20-30%, and improvement in OS was not shown.
Romidepsin and the hypomethylating agent CC-486 (5-azacitidine) acted synergistically in vitro, and showed high clinical activity, with an ORR of up to 79% in some types of TCL.
Many TCLs rely on the PI3K pathway, whether through activation of CD28 through fusions or gain-of-function mutations or by interruptions of the CD28-inhibiting PD-1/PD-L1 immune checkpoint.
Duvelisib is an inhibitor of the PI3K gamma and delta isoforms; in phase I trials it has shown both single-agent activity and synergy with romidepsin for patients with TCL.
As combinations of both CC-486 (5-azacitidine)/romidepsin and duvelisib/romidepsin have demonstrated both adequate safety and clinical efficacy, safety and efficacy of the triplet combination should be explored.
Objectives:
To determine the safety and toxicity profile, maximum tolerated dose (MTD), and the recommended phase II dose (RP2D) of the four-drug combination of CC-486 (5-azacitidine), romidepsin and duvelisib, and doxorubicin, in patients with TCL.
Eligibility:
Patients with histologically or cytologically confirmed newly diagnosed or relapsed/refractory T-cell lymphoma (TCL) defined as follows:
Cohort 2: Untreated patients with any peripheral TCL, not including anaplastic large cell lymphoma (ALCL), but including acute and lymphoma subtypes of adult T-cell leukemia/lymphoma (ATLL).
Cohorts 1 and 3: Any relapsed/refractory peripheral T-cell lymphoma including ATLL and ALCL who have disease after receiving at least one line of systemic therapy, which must include brentuximab vedotin if the disease is ALCL.
Age >= 18 years of age
ECOG performance status of <= 2
Adequate organ and marrow function
Design:
Open-label, single-center, non-randomized Phase 1 study
"3 + 3" design will be used to determine the RP2D of dose-escalated duvelisib with fixed dose romidepsin CC-486 (5-azacitidine) and doxorubicin with two expansion cohorts at the RP2D
Maximum 8 cycles (21-day cycles) of combination therapy
To explore all dose levels, including further evaluation in two dose expansion cohorts, the accrual ceiling will be set at 60 patients
- Conditions
- Adult T-cell Leukemia/Lymphoma, Extranodal NK-/T-cell Lymphoma, Nasal Type, Enteropathy-Associated T-Cell Lymphoma, Monomorphic Epiteliotrophic Intestinal T-cell Lymphoma, Hepatosplenic T-cell Lymphoma
- Being tested
- CC-486 (5-azacitidine), Duvelisib, Romidepsin, Doxorubicin
- Keywords
- TCL, Histone Deacetylase Inhibitors (HDACi), Kinase Inhibitors
- Medical subject headings
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Extranodal NK-T-Cell, Enteropathy-Associated T-Cell Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CC-486 (5-azacitidine)Drug
CC-486 (5-azacitidine) with a dose of 300mg oral intake daily will be given on day 1 to day 10 for 8 cycles.
DuvelisibDrug
Duvelisib by oral intake at escalating doses of 25, 50 and 75 mg/BID on days -14 to 14 of the 1st cycle then days 1-14 of Cycles 2-8 of each 21- day cycle (max 8 cycles).
RomidepsinDrug
Romidepsin (12mg/m2) will be administered on days 1 and 8 of each cycle through a peripheral or central intravenous catheter for 8 cycles.
DoxorubicinDrug
Doxorubicin at 25 mg/ m2 by IV infusion on Day 1 of cycles 3-8.
| Study group | Role | What they receive |
|---|---|---|
| 1- Experimental Treatment: Dose Escalation | Experimental | Duvelisib (PO BID) at escalating doses of 25, 50 and 75 mg/BID on days -14 to 14 of C1 and days 1-14 of all other cycles of each 21- day cycle (max 8 cycles) with CC-486 (5-azacitidine) (PO) at 300mg/day on days 1-10, romidepsin at 12mg/m2 (IV) on Days 1 and 8 of each cycle and doxorubicin (IV) at 25 mg/ m2 on Day 1 of cycles 3-8 (Cycles 3-6 for patients with prior anthracycline-based therapy), to determine RP2D of duvelisib and doxorubicin Receives: Drug: CC-486 (5-azacitidine); Drug: Duvelisib; Drug: Romidepsin; Drug: Doxorubicin |
| 2 - Experimental Treatment: Dose Expansion | Experimental | Duvelisib (PO BID) at RP2D on days -14 to 14 of C1 and days 1-14 of all other 21-day cycle (max 8 cycles) with CC-486 (5-azacitidine) at 300mg/day (PO) on days 1-10, romidepsin at 12mg/m2 (IV) on days 1 and 8 of each cycle, and doxorubicin at 25 mg/m2 on day 1 of Cycles 3-8 (Cycles 3-6 for patients with prior anthracycline-based therapy Receives: Drug: CC-486 (5-azacitidine); Drug: Duvelisib; Drug: Romidepsin; Drug: Doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability
Rate and severity of AEs will be summarized by grade and type of toxicity
Measured: 8 cycles
Maximum tolerated dose (MTD)
Frequency (number and percentage) of treatment emergent adverse events
Measured: 21 days
Secondary outcomes (6)
Progression-free survival
The response rate will be determined and reported along with a 95% confidence interval
Measured: every 2 months for 6 months, every 3 months for 2 years, every 6 months for 2 years, then annually
Overall Repsonse Rate
The response rate will be determined and reported along with a 95% confidence interval
Measured: 8 cycles
Complete Response Rate
The response rate will be determined and reported along with a 95% confidence interval
Measured: 8 cycles
Duration of response (DOR)
The response rate will be determined and reported along with a 95% confidence interval
Measured: every 2 months for 6 months, every 3 months for 2 years, every 6 months for 2 years, then annually
Overall Survival (OS)
The response rate will be determined and reported along with a 95% confidence interval
Measured: every 2 months for 6 months, every 3 months for 2 years, every 6 months for 2 years, then annually
Event Free Survival (EFS)
The response rate will be determined and reported along with a 95% confidence interval
Measured: every 2 months for 6 months, every 3 months for 2 years, every 6 months for 2 years, then annually
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2020
- Study start3 Nov 2022
- Primary completion3 Nov 2022
- Study completion3 Nov 2022
Why it stopped: Safety issues with PI3 kinase inhibitors
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult T-cell Leukemia/LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kevin C Conlon, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04639843
- Sponsor's protocol ID
- 200169
- Other IDs
- 20-C-0169
- Status last verified
- Nov 2022
- First submitted
- 20 Nov 2020
- Last updated
- 4 Nov 2022
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: .All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@All collected IPD will be shared with collaborators under the terms of collaborative agreements.
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Doxorubicin, CC-486 (5-azacitidine), Romidepsin, and Duvelisib (hARD) for T-cell Lymphoma
- ClinicalTrials.gov ID
- NCT04639843
- Acronym / sponsor ID
- 200169
- Conditions
- Adult T-cell Leukemia/Lymphoma, Extranodal NK-/T-cell Lymphoma, Nasal Type, Enteropathy-Associated T-Cell Lymphoma, Monomorphic Epiteliotrophic Intestinal T-cell Lymphoma, Hepatosplenic T-cell Lymphoma
- Keywords
- TCL, Histone Deacetylase Inhibitors (HDACi), Kinase Inhibitors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Safety issues with PI3 kinase inhibitors
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 3 Nov 2022 (actual)
- Primary completion
- 3 Nov 2022 (actual)
- Study completion
- 3 Nov 2022 (actual)
- First posted
- 23 Nov 2020 (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.
Background:
T-cell lymphomas (TCLs) are rare cancers. Many types of TCLs do not develop in the lymph nodes but in places like the skin, spleen, and bone marrow. Researchers want to see if a mix of 4 drugs can help people with TCL.
Objective:
To test if the combination of romidepsin, CC-486 (5-azacitidine), duvelisib, and doxorubicin can be used safely in people with TCL.
Eligibility:
Adults 18 and older with TCL that is newly diagnosed or that returned after or did not respond to standard treatments.
Design:
Participants will be screened on a separate protocol. They may have a tumor biopsy.
Participants will have medical histories, medicine reviews, and physical exams. Their ability to do daily activities will be assessed. They will have blood and urine tests.
Participants will take duvelisib and CC-486 (5-azacitidine) by mouth. They will get romidepsin and doxorubicin by intravenous infusion. They will take the drugs for up to eight 21-day cycles. They will keep a medicine diary.
Participants will have a bone marrow aspiration and/or biopsy. Bone marrow will be taken through a needle inserted in the hip.
Participants will have tumor imaging scans. Some may have a brain MRI and lumbar puncture. Some may have skin assessments.
Participants will give blood, saliva, and tumor samples for research.
Participants will have a safety visit 30 days after treatment ends. Then they will have follow-up visits every 60 days for 6 months, then every 90 days for 2 years, and then every 6 months for 2 years. Then they will have yearly visits until their disease gets worse or they start a new treatment....
Detailed description
Background:
T-cell lymphomas (TCLs) are a heterogeneous group of lymphoid malignancies defined by clonal proliferation of post-thymic T lymphocytes.
Patients with newly diagnosed TCLs are most commonly treated with a CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone)-like regimen, with less than 30% having durable complete responses (CRs). Of the chemotherapy agents used, doxorubicin is the one which was consistently associated with prolonged progression-free survival (PFS) and overall survival (OS) in retrospective studies.
Treatment options for the 70% of patients with TCL who relapse are limited and of minimal efficacy; novel treatment strategies are urgently needed.
Many TCL have mutations in epigenetic modifier genes, and histone deacetylase inhibitors such as romidepsin are approved for treatment of peripheral T-cell lymphoma (PTCL); however, the overall response rate (ORR) with single-agent treatment is only 20-30%, and improvement in OS was not shown.
Romidepsin and the hypomethylating agent CC-486 (5-azacitidine) acted synergistically in vitro, and showed high clinical activity, with an ORR of up to 79% in some types of TCL.
Many TCLs rely on the PI3K pathway, whether through activation of CD28 through fusions or gain-of-function mutations or by interruptions of the CD28-inhibiting PD-1/PD-L1 immune checkpoint.
Duvelisib is an inhibitor of the PI3K gamma and delta isoforms; in phase I trials it has shown both single-agent activity and synergy with romidepsin for patients with TCL.
As combinations of both CC-486 (5-azacitidine)/romidepsin and duvelisib/romidepsin have demonstrated both adequate safety and clinical efficacy, safety and efficacy of the triplet combination should be explored.
Objectives:
To determine the safety and toxicity profile, maximum tolerated dose (MTD), and the recommended phase II dose (RP2D) of the four-drug combination of CC-486 (5-azacitidine), romidepsin and duvelisib, and doxorubicin, in patients with TCL.
Eligibility:
Patients with histologically or cytologically confirmed newly diagnosed or relapsed/refractory T-cell lymphoma (TCL) defined as follows:
Cohort 2: Untreated patients with any peripheral TCL, not including anaplastic large cell lymphoma (ALCL), but including acute and lymphoma subtypes of adult T-cell leukemia/lymphoma (ATLL).
Cohorts 1 and 3: Any relapsed/refractory peripheral T-cell lymphoma including ATLL and ALCL who have disease after receiving at least one line of systemic therapy, which must include brentuximab vedotin if the disease is ALCL.
Age >= 18 years of age
ECOG performance status of <= 2
Adequate organ and marrow function
Design:
Open-label, single-center, non-randomized Phase 1 study
"3 + 3" design will be used to determine the RP2D of dose-escalated duvelisib with fixed dose romidepsin CC-486 (5-azacitidine) and doxorubicin with two expansion cohorts at the RP2D
Maximum 8 cycles (21-day cycles) of combination therapy
To explore all dose levels, including further evaluation in two dose expansion cohorts, the accrual ceiling will be set at 60 patients
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1- Experimental Treatment: Dose Escalation | Experimental | Drug: CC-486 (5-azacitidine), Drug: Duvelisib, Drug: Romidepsin, Drug: DoxorubicinDuvelisib (PO BID) at escalating doses of 25, 50 and 75 mg/BID on days -14 to 14 of C1 and days 1-14 of all other cycles of each 21- day cycle (max 8 cycles) with CC-486 (5-azacitidine) (PO) at 300mg/day on days 1-10, romidepsin at 12mg/m2 (IV) on Days 1 and 8 of each cycle and doxorubicin (IV) at 25 mg/ m2 on Day 1 of cycles 3-8 (Cycles 3-6 for patients with prior anthracycline-based therapy), to determine RP2D of duvelisib and doxorubicin |
| 2 - Experimental Treatment: Dose Expansion | Experimental | Drug: CC-486 (5-azacitidine), Drug: Duvelisib, Drug: Romidepsin, Drug: DoxorubicinDuvelisib (PO BID) at RP2D on days -14 to 14 of C1 and days 1-14 of all other 21-day cycle (max 8 cycles) with CC-486 (5-azacitidine) at 300mg/day (PO) on days 1-10, romidepsin at 12mg/m2 (IV) on days 1 and 8 of each cycle, and doxorubicin at 25 mg/m2 on day 1 of Cycles 3-8 (Cycles 3-6 for patients with prior anthracycline-based therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (33 listed)
- Patients who are receiving any other investigational agents.
- Patients in need of immediate cytoreduction.
- Chemotherapy or monoclonal antibody therapy within 4 weeks prior to start of treatment (6 weeks for nitrosoureas or mitomycin C); small molecule or radiation therapy within 2 weeks.
- Prior lifetime doxorubicin therapy >= 400 mg/m^2.
- Prior radiation therapy to chest with fields involving the heart.
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 |
|---|---|---|
| CC-486 (5-azacitidine)CC-486 (5-azacitidine) with a dose of 300mg oral intake daily will be given on day 1 to day 10 for 8 cycles. | Drug | 1- Experimental Treatment: Dose Escalation, 2 - Experimental Treatment: Dose Expansion |
| DuvelisibDuvelisib by oral intake at escalating doses of 25, 50 and 75 mg/BID on days -14 to 14 of the 1st cycle then days 1-14 of Cycles 2-8 of each 21- day cycle (max 8 cycles). | Drug | 1- Experimental Treatment: Dose Escalation, 2 - Experimental Treatment: Dose Expansion |
| RomidepsinRomidepsin (12mg/m2) will be administered on days 1 and 8 of each cycle through a peripheral or central intravenous catheter for 8 cycles. | Drug | 1- Experimental Treatment: Dose Escalation, 2 - Experimental Treatment: Dose Expansion |
| DoxorubicinDoxorubicin at 25 mg/ m2 by IV infusion on Day 1 of cycles 3-8. | Drug | 1- Experimental Treatment: Dose Escalation, 2 - Experimental Treatment: Dose Expansion |
Primary outcome
Safety and tolerability
Time frame: 8 cycles
Rate and severity of AEs will be summarized by grade and type of toxicity
Maximum tolerated dose (MTD)
Time frame: 21 days
Frequency (number and percentage) of treatment emergent adverse events
6 secondary outcomes
Progression-free survival
Time frame: every 2 months for 6 months, every 3 months for 2 years, every 6 months for 2 years, then annually
Overall Repsonse Rate
Time frame: 8 cycles
Complete Response Rate
Time frame: 8 cycles
Duration of response (DOR)
Time frame: every 2 months for 6 months, every 3 months for 2 years, every 6 months for 2 years, then annually
Overall Survival (OS)
Time frame: every 2 months for 6 months, every 3 months for 2 years, every 6 months for 2 years, then annually
Event Free Survival (EFS)
Time frame: every 2 months for 6 months, every 3 months for 2 years, every 6 months for 2 years, then annually
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 4 Nov 2022.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. .All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@All collected IPD will be shared with collaborators under the terms of collaborative agreements.
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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.
Kevin C Conlon, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CC-486 (5-azacitidine), Duvelisib and Romidepsin in people with Adult T-cell Leukemia/Lymphoma and Extranodal NK-/T-cell Lymphoma, Nasal Type, run by National Cancer Institute (NCI) 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 0 inclusion and 33 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 4 Nov 2022. 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 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.
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?
Safety and tolerability (time frame: 8 cycles). 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 4 Nov 2022.