Clinical Trials /

Study of Ixazomib and Romidepsin in Peripheral T-cell Lymphoma (PTCL)

NCT03547700

Description:

Single arm phase I/II study of ixazomib and romidepsin in relapsed/refractory PTCL. Each cycle is 28 days. Patients will continue to receive therapy until progressive disease, unacceptable toxicity, or if any other withdrawal criteria are met. The phase I study includes three dose levels. The phase II study will include treatment with ixazomib and romidepsin at the MTD established in the Phase I study.

Related Conditions:
  • Peripheral T-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Ixazomib and Romidepsin in Peripheral T-cell Lymphoma (PTCL)
  • Official Title: Phase I/II Study of Ixazomib and Romidepsin in Relapsed/ Refractory Peripheral T-cell Lymphoma (PTCL)

Clinical Trial IDs

  • ORG STUDY ID: BTCRC-HEM15-028
  • NCT ID: NCT03547700

Conditions

  • Lymphoma, T-Cell, Peripheral

Interventions

DrugSynonymsArms
RomidepsinIstodaxRomidepsin plus Ixazomib
IxazomibNinlaroRomidepsin plus Ixazomib

Purpose

Single arm phase I/II study of ixazomib and romidepsin in relapsed/refractory PTCL. Each cycle is 28 days. Patients will continue to receive therapy until progressive disease, unacceptable toxicity, or if any other withdrawal criteria are met. The phase I study includes three dose levels. The phase II study will include treatment with ixazomib and romidepsin at the MTD established in the Phase I study.

Trial Arms

NameTypeDescriptionInterventions
Romidepsin plus IxazomibExperimentalThe 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.
  • Romidepsin
  • Ixazomib

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: Assess adverse events
Time Frame:12 months
Safety Issue:
Description:To evaluate the safety of ixazomib when given in combination with romidepsin to establish the maximum tolerated dose (MTD) of this combination, per CTCAE v4.

Secondary Outcome Measures

Measure:Phase II: Overall Response Rate (ORR)
Time Frame:36 months
Safety Issue:
Description: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.
Measure:Phase II: Duration of Response (DOR)
Time Frame:36 months
Safety Issue:
Description:DOR, defined as time that measurement criteria are met for complete or partial metabolic response (whichever status is recorded first) until disease progression/recurrence or initiation of new antineoplastic therapy, as per the Lugano response criteria.
Measure:Phase II: Time To Next Treatment (TTNT)
Time Frame:36 months
Safety Issue:
Description:TTNT defined as the date of initiation of treatment until death or the date of initiation of the next treatment.
Measure:Phase II: Overall Survival (OS)
Time Frame:36 months
Safety Issue:
Description:OS, defined as time from first day of treatment to time of death.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ryan Wilcox

Last Updated

February 7, 2020