Study of Ixazomib and Romidepsin in Peripheral T-cell Lym... | NCT03547700

NCT03547700

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Takeda	INDUSTRY
Big Ten Cancer Research Consortium	OTHER

Label	Type	Description	Intervention Names
Phase I: Romidepsin plus Ixazomib	Experimental	The phase I study includes three dose levels (DL) for romidepsin: DL4: 10 mg/m2 on Days 1, 8, 15; DL5: 14 mg/m2 Days 1, 8; DL6: 14 mg/m2 Days 1, 8, 15. Ixazomib is 4 mg PO Days 1, 8, 15. The phase II study will include treatment with ixazomib and romidepsin at the MTD established in the Phase I study. Each cycle is 28 days and patients will receive treatment until progressive disease, unacceptable toxicity, or if any other withdrawal criteria are met.	Drug: Romidepsin Drug: Ixazomib

Name	Type	Description	Arm Group Labels	Other Names
Romidepsin	Drug	Romidepsin is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the modulation of gene expression.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Phase I: Maximum Tolerated Dose (MTD)	MTD is the dose level with a model-estimated rate of Dose Limiting Toxicities (DLT) closest to 25% after 36 patients have been enrolled. The maximum tolerated dose could not be determined because the trial was terminated early, however the number of participants who experienced DLTs found at each dose level is reported in a new outcome measure.	From first dose of treatment through the 1st cycle (28 days)
Phase II: Complete Response Rate (CR)	The complete response (CR) rate of this combination in relapsed/refractory PTCL is defined as complete metabolic response recorded from first day of treatment until disease progression or initiation of new antineoplastic therapy, as per the Lugano response criteria.	36 months

Secondary Outcomes

Measure	Description	Time Frame
Phase II: Overall Response Rate (ORR)	OR, defined as complete or partial metabolic response recorded from first day of treatment until disease progression/recurrence or initiation of new antineoplastic therapy, as per the Lugano response criteria.	36 months
Phase II: Duration of Response (DOR)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
Age ≥ 18 years at the time of consent.
ECOG Performance Status of 0-2 within 14 days prior to registration.
Histological confirmation of peripheral T-cell lymphoma (PTCL) and biopsy confirmation of disease relapse (after initial or any subsequent salvage therapy).
Documented disease progression after receiving at least one prior therapeutic regimen.
Prior cancer treatment must be completed at least 28 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or baseline. Systemic steroids at a dose less than the equivalent of 10 mg/day of prednisone and inhaled, nasal, and topical steroids are permitted. Intermittent dexamethasone for the treatment of nausea/emesis is also permitted.
Absolute Neutrophil Count (ANC) ≥ 1000/mm3
Platelets (Plt) ≥ 75,000/mm3
Calculated creatinine clearance ≥ 30 cc/min using the Cockcroft-Gault formula
Bilirubin ≤ 1.5 × upper limit of normal (ULN), (exception of Gilbert disease)
Aspartate aminotransferase (AST) ≤ 3 × ULN, if known hepatic involvement then ≤ 5 × ULN
Alanine aminotransferase (ALT) ≤ 3 × ULN, if known hepatic involvement then ≤ 5 × ULN
Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
Males must be willing to abstain from donating sperm or semen from the time of informed consent until 90 days after treatment discontinuation.
The subject must have the ability to understand and comply with study procedures for the entire length of the study, as determined by the treating physician or protocol designee.

Exclusion Criteria:

A history of, or a concurrent, clinically significant illness, medical condition or laboratory abnormality that, in the investigator's opinion, could affect the conduct of the study.
Active infection requiring systemic therapy
Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least two years.
Active central nervous system (CNS) lymphoma
Major surgery or radiation therapy within 28 days of study registration
Uncontrolled infectious disease, including active herpes simplex or herpes zoster
Known positive test for Hepatitis B surface antigen, Hepatitis C, or HIV. NOTE: testing is not required.
Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of oral medications including difficulty swallowing, as determined by the treating physician.
Evidence of uncontrolled cardiovascular conditions, including uncontrolled hypertension, cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
Q-T interval, based on Bazett-corrected interval > 0.45 sec
Treatment with any investigational drug within 28 days prior to registration.
Peripheral neuropathy ≥ grade 2
Prior treatment with bortezomib, ixazomib, or romidepsin.
Systemic treatment, within 14 days, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort.
Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
Prior autologous hematopoietic stem cell transplant within 90 days of study registration.
Prior allogeneic hematopoietic stem cell transplant.

Name	Affiliation	Role
Ryan Wilcox, MD, PhD	University of Michigan Rogel Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Illinois Cancer Center		Chicago	Illinois	60612	United States
Indiana University Melvin and Bren Simon Cancer Center

Arm/Group Information

ID	Title	Description
FG000	Phase I Dose Level 4:Romidepsin 10mg/m² IV on Days 1, 8, 15; Ixazomib 4 mg PO on Days 1, 8, 15	Romidepsin 10mg/m² IV on days 1, 8, 15: Romidepsin is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the modulation of gene expression. Ixazomib 4 mg PO on days 1, 8, 15: Ixazomib is a reversible proteasome inhibitor. Ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome.
FG001	Phase I Dose Level 5: Romidepsin 14mg/m² IV on Days 1, 8; Ixazomib 4 mg PO on Days 1, 8, 15	Romidepsin 14mg/m² IV on days 1, 8: Romidepsin is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the modulation of gene expression. Ixazomib 4 mg PO on days 1, 8, 15: Ixazomib is a reversible proteasome inhibitor. Ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome.
FG002	Phase I Dose Level 6: Romidepsin 14mg/m² IV on Days 1, 8, 15; Ixazomib 4 mg PO on Days 1, 8, 15	Romidepsin 14mg/m² IV on days 1, 8, 15: Romidepsin is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the modulation of gene expression. Ixazomib 4 mg PO on days 1, 8, 15: Ixazomib is a reversible proteasome inhibitor. Ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Phase I Dose Level 4:Romidepsin 10mg/m² IV on Days 1, 8, 15; Ixazomib 4 mg PO on Days 1, 8, 15	Romidepsin 10mg/m² IV on days 1, 8, 15: Romidepsin is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the modulation of gene expression. Ixazomib 4 mg PO on days 1, 8, 15: Ixazomib is a reversible proteasome inhibitor. Ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Median

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Phase I: Maximum Tolerated Dose (MTD)

MTD is the dose level with a model-estimated rate of Dose Limiting Toxicities (DLT) closest to 25% after 36 patients have been enrolled.

The maximum tolerated dose could not be determined because the trial was terminated early, however the number of participants who experienced DLTs found at each dose level is reported in a new outcome measure.

Posted

Number

mg/m^2

From first dose of treatment through the 1st cycle (28 days)

ID	Title	Description
OG000	All Subjects Treated	Romidepsin dose of either 10mg/m², 14mg/m² IV on days 1, 8, 15, or 14mg/m² on days 1 and 8 : Romidepsin is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the modulation of gene expression. Ixazomib 4 mg PO on days 1, 8, 15: Ixazomib is a reversible proteasome inhibitor. Ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase I Dose Level 4: Romidepsin 10mg/m² IV on Days 1, 8, 15; Ixazomib 4 mg PO on Days 1, 8, 15	Romidepsin 10mg/m² IV on days 1, 8, 15: Romidepsin is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the modulation of gene expression. Ixazomib 4 mg PO on days 1, 8, 15: Ixazomib is a reversible proteasome inhibitor. Ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome.

ID	Term
D016399	Lymphoma, T-Cell
D008228	Lymphoma, Non-Hodgkin
D008223	Lymphoma
D009370	Neoplasms by Histologic Type