Ignite Creation Date:
2024-05-06 @ 2:50 PM
Last Modification Date:
2024-10-26 @ 1:38 PM
Study NCT ID:
NCT04447027
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-06-05
First Post:
2020-06-24
Brief Title:
Romidepsin CC-486 5-azacitidine Dexamethasone and Lenalidomide RAdR for RelapsedRefractory T-cell Malignancies
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase 1 Study of Romidepsin CC-486 5-azacitidine Dexamethasone and Lenalidomide RAdR for RelapsedRefractory T-cell Malignancies
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-07-18
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Mature T-cell malignancies TCMs are a rare group of cancers that usually do not have effective treatments or cures Because of this participants with TCMs often relapse and have a poor overall prognosis This trial is testing if combining several drugs against TCMs can be a more effective
Primary Objective
To test if the combination of romidepsin CC-486 5-azacitidine dexamethasone and lenalidomide RAdR can be given safely to participants with relapsed or treatment refractory TCM
Other Secondary Objective
Measure the activity of this combination treatment
Eligibility
People age 18 and older who have a failed or relapsed after standard treatments for mature TCMs
Design
Participants will be screened for eligibility by performing the following tests or procedures
Physical exam
Medical history
Medicine review
Blood and urine tests
Symptom review
Bone marrow examination
Total Body imaging scans or x-rays
Tumor biopsy
Participants will have blood tests during treatment to make sure their blood cell counts are okay
Romidepsin is infused through an IV placed in one of the veins usually in the arm Lenalidomide dexamethasone and CC-486 5-azacitidine are pills or capsules taken by mouth
Participants are asked to keep a diary of when they take their pills to make sure they are taking these medicines properly
Participants will have tumor imaging scans after every 2nd cycle or 6 weeks to check if the treatment is working If the doctors are concerned the cancer has spread to the brain andor spine they will have scans of the areas and a sampling of the fluid around the brainspine which is obtained through a small needle inserted into the lower part of the back for a short time to collect the fluid This procedure is called a spinal tap or lumbar puncture
Participants who have tumor in their skin will have repeat exams of their skin and sometimes photographs taken of these areas to see if the treatment is working
Participants will also be asked to give blood saliva and sometimes have optional biopsies of their tumor where these tests are done for research purposes
After they have completed the protocol treatment 6 cycles they will be asked to return to clinic 30 days after treatment has ended then every other month or 60 days for the first 6 months then every 3 months 90 days for 2 years and then every 6 months for years 2 to 4 after completing treatment After 45 years they will be seen once a year
Mature T-cell malignancies TCMs are a rare group of cancers that usually do not have effective treatments or cures Because of this participants with TCMs often relapse and have a poor overall prognosis This trial is testing if combining several drugs against TCMs can be a more effective
Primary Objective
To test if the combination of romidepsin CC-486 5-azacitidine dexamethasone and lenalidomide RAdR can be given safely to participants with relapsed or treatment refractory TCM
Other Secondary Objective
Measure the activity of this combination treatment
Eligibility
People age 18 and older who have a failed or relapsed after standard treatments for mature TCMs
Design
Participants will be screened for eligibility by performing the following tests or procedures
Physical exam
Medical history
Medicine review
Blood and urine tests
Symptom review
Bone marrow examination
Total Body imaging scans or x-rays
Tumor biopsy
Participants will have blood tests during treatment to make sure their blood cell counts are okay
Romidepsin is infused through an IV placed in one of the veins usually in the arm Lenalidomide dexamethasone and CC-486 5-azacitidine are pills or capsules taken by mouth
Participants are asked to keep a diary of when they take their pills to make sure they are taking these medicines properly
Participants will have tumor imaging scans after every 2nd cycle or 6 weeks to check if the treatment is working If the doctors are concerned the cancer has spread to the brain andor spine they will have scans of the areas and a sampling of the fluid around the brainspine which is obtained through a small needle inserted into the lower part of the back for a short time to collect the fluid This procedure is called a spinal tap or lumbar puncture
Participants who have tumor in their skin will have repeat exams of their skin and sometimes photographs taken of these areas to see if the treatment is working
Participants will also be asked to give blood saliva and sometimes have optional biopsies of their tumor where these tests are done for research purposes
After they have completed the protocol treatment 6 cycles they will be asked to return to clinic 30 days after treatment has ended then every other month or 60 days for the first 6 months then every 3 months 90 days for 2 years and then every 6 months for years 2 to 4 after completing treatment After 45 years they will be seen once a year
Detailed Description:
Background
Mature T-cell malignancies TCM are rare and heterogeneous group of leukemias and lymphomas accounting for 5 to 10 of all lymphomas in the US
Patients with systemic TCM are most commonly treated with a CHOP cyclophosphamide doxorubicin vincristine and prednisone-like regimens that produce long-term progression-free survival in about 30 of these cases
Patients with relapsedrefractory RR TCM have very poor prognosis with median overall survival of less than 1 year Treatment options for RR TCM are very few and of limited efficacy thus novel treatment strategies are urgently needed
Mutations in epigenetic regulators are common in aggressive TCMs and standard treatment with histone deacetylase inhibitors HDACi such as romidepsin show modest clinical activity with single agent the overall response ORR around 25
Combination of romidepsin and 5-azacitidine hypomethylating agents was synergistic in preclinical models and has demonstrated high clinical activity with an ORR of 79
Many TCMs rely on The Ikaros-dependent NF-kBIRF4 signaling pathway to maintain proliferation which is why lenalidomide which induces degradation of Ikaros and downregulates IRF4 has single agent activity in RR TCM with ORR of 26 to 42 depending on the subtype
Lenalidomide synergizes with romidepsin and enhances tumor cell death in TCM cell lines predicting that the addition of lenalidomide to the established romidepsin CC-486 5-azacitidine combination will further improve efficacy
Objectives
-To determine the safety and toxicity profile and the maximum tolerated dose MTD of the four drug combination of CC-486 5-azacitidine romidepsin lenalidomide and dexamethasone in patients with TCM
Eligibility
Refractoryrelapsed TCM excluding in Cutaneous T-Cell Lymphoma defined as follows
Patients with systemic disease
Have received at least one line of prior therapy
Must have received brentuximab vedotin if the disease is anaplastic large cell lymphoma or CD30-positive cutaneous T-cell lymphoma
Age 18 years of age
ECOG performance status of 2 or 3 if decrease is due to the disease
Histologically or cytologically confirmed relapsed andor refractory mature TCM
Adequate organ and marrow function
Design
Open-label single-center uncontrolled Phase 1 study
3 3 design will be used to determine the MTD of dose-escalated lenalidomide with fixed dose of romidepsin and CC-486 5-azacitidine
An expansion cohort of 9 patients will be evaluated at the MTD
Maximum 6 cycles 28-day cycle of combination therapy
To explore all dose levels including further evaluation in a dose expansion cohort the accrual ceiling will be set at 30 patients
Mature T-cell malignancies TCM are rare and heterogeneous group of leukemias and lymphomas accounting for 5 to 10 of all lymphomas in the US
Patients with systemic TCM are most commonly treated with a CHOP cyclophosphamide doxorubicin vincristine and prednisone-like regimens that produce long-term progression-free survival in about 30 of these cases
Patients with relapsedrefractory RR TCM have very poor prognosis with median overall survival of less than 1 year Treatment options for RR TCM are very few and of limited efficacy thus novel treatment strategies are urgently needed
Mutations in epigenetic regulators are common in aggressive TCMs and standard treatment with histone deacetylase inhibitors HDACi such as romidepsin show modest clinical activity with single agent the overall response ORR around 25
Combination of romidepsin and 5-azacitidine hypomethylating agents was synergistic in preclinical models and has demonstrated high clinical activity with an ORR of 79
Many TCMs rely on The Ikaros-dependent NF-kBIRF4 signaling pathway to maintain proliferation which is why lenalidomide which induces degradation of Ikaros and downregulates IRF4 has single agent activity in RR TCM with ORR of 26 to 42 depending on the subtype
Lenalidomide synergizes with romidepsin and enhances tumor cell death in TCM cell lines predicting that the addition of lenalidomide to the established romidepsin CC-486 5-azacitidine combination will further improve efficacy
Objectives
-To determine the safety and toxicity profile and the maximum tolerated dose MTD of the four drug combination of CC-486 5-azacitidine romidepsin lenalidomide and dexamethasone in patients with TCM
Eligibility
Refractoryrelapsed TCM excluding in Cutaneous T-Cell Lymphoma defined as follows
Patients with systemic disease
Have received at least one line of prior therapy
Must have received brentuximab vedotin if the disease is anaplastic large cell lymphoma or CD30-positive cutaneous T-cell lymphoma
Age 18 years of age
ECOG performance status of 2 or 3 if decrease is due to the disease
Histologically or cytologically confirmed relapsed andor refractory mature TCM
Adequate organ and marrow function
Design
Open-label single-center uncontrolled Phase 1 study
3 3 design will be used to determine the MTD of dose-escalated lenalidomide with fixed dose of romidepsin and CC-486 5-azacitidine
An expansion cohort of 9 patients will be evaluated at the MTD
Maximum 6 cycles 28-day cycle of combination therapy
To explore all dose levels including further evaluation in a dose expansion cohort the accrual ceiling will be set at 30 patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 20-C-0127 | None | None | None |