Dose-Escalation Trial of Carfilzomib With and Without Romidepsin in Cutaneous T-Cell Lymphoma

NCT01738594 | Terminated Phase 1 Results DMC

• 3 other identifiers: NU 12H06STU00071042NCI-2012-01952
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase I trial studies the side effects and the best dose of carfilzomib when given together with or without romidepsin in treating patients with stage IA-IVB cutaneous T-cell lymphoma. Carfilzomib and romidepsin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving carfilzomib alone is more effective than when given together with romidepsin.

Conditions

Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Dose Limiting Toxicities (DLTs)

  To determine the maximum tolerated dose (MTD) by assessing the adverse events experienced by patients of both carfilzomib alone and when taken with romidepsin for dose limiting toxicities (DLT) on days 1 and 15 of the first 28 days of treatment. Toxicities will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. DLT is defined as any of the following: Grade ≥ 2 neuropathy with pain Grade ≥ 3 non-hematologic toxicity Grade ≥ 3 nausea, vomiting, or diarrhea not controlled Grade ≥ 4 fatigue persisting for \> 7 days Grade 4 neutropenia (ANC \< 500/mm3) occurring for \>7 days Febrile neutropenia \[ANC \< 1000/mm3 with fever Grade ≥ 3 thrombocytopenia persisting for \> 7 days Grade ≥ 3 thrombocytopenia associated with bleeding Any toxicity requiring a dose reduction within Cycle 1 Inability to receive Cycle 2, Day 1 dose due to drug related toxicity persisting from Cycle 1 or drug-related toxicity newly encountered on Cycle 2, Day 1

  During the first 28 days (1 cycle=28 days) of treatment.

Secondary Outcomes (3)

• Overall Response Rate (ORR) of the Disease When Treated With Carfilzomib Alone and When Taken With Romidepsin

  Baseline and every 56 days (2 cycles) while on treatment and up to 4 cycles

• Duration of Response of the Disease When Treated With Carfilzomib Alone and When Taken With Romidepsin

  Baseline and every 56 days (2 cylces) until disease progression

• Time to Progression (TTP) of the Disease When Treated With Carfilzomib Alone and When Taken With Romidepsin

  Baseline and every 56 days (2 cycles) until disease progression or toxicity call for discontinuation of treatment

Other Outcomes (1)

• Proteasome Activity Will be Measured in Peripheral Blood and Tumor Tissue Samples to Observe Proteasome Inhibition While on Treatment

  Blood is collected before & after carfilzomib dosing during cycle 1 (days 1, 2, & 8) & cycle 2 (day 1) & Tumor tissue samples obtained at baseline, 1-4 hours post-first dose of carfilzomib (cycle 1 day 1) & 1-4 hours post-carfilzomib on cycle 1 day 8

Study Arms (2)

Arm A (carfilzomib)

EXPERIMENTAL

Patients receive carfilzomib IV over 2-10 minutes on days 1, 2, 8, 9, 15, and 16.

Drug: carfilzomib; Other: laboratory biomarker analysis

Arm B (carfilzomib, romidepsin)

EXPERIMENTAL

Patients receive carfilzomib as in Arm A and romidepsin IV over 4 hours on days 1, 8, and 15.

Drug: carfilzomib; Drug: romidepsin; Other: laboratory biomarker analysis

Interventions

carfilzomib DRUG

Given IV

Also known as: Kyprolis, PR-171

Arm A (carfilzomib); Arm B (carfilzomib, romidepsin)

romidepsin DRUG

Given IV

Also known as: FK228, FR901228, Istodax

Arm B (carfilzomib, romidepsin)

laboratory biomarker analysis OTHER

Correlative studies

Arm A (carfilzomib); Arm B (carfilzomib, romidepsin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histological confirmation of a cutaneous T-cell lymphoma (CTCL) of any histology; confirmation of histological diagnosis must be completed prior to enrollment by the lead site (Northwestern)
• Patients will be stratified by mycosis fungoides (MF) and Sezary syndrome (SS) (report diagnostic or consistent with MF/SS), stage IA-IVB according to TNM blood (TNMB) classification versus other CTCL histologies
• Patients must have measurable disease (using modified Severity-Weighted Assessment Tool \[mSWAT\]) and/or use of indicator lesions must be designated prior to study enrollment (from imaging); measurable disease upon physical exam with a negative scan is acceptable
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Patients must have a life expectancy of \>= 3 months
• Patients with MF/SS must have failed at least 1 prior topical therapy (including steroids, nitrogen mustard, retinoids, phototherapy, photochemotherapy, radiation, and total skin electron beam); there is no upper limit for prior therapies
• Serum creatinine =\< 2.0 mg/dL
• Total bilirubin =\< 2.2 mg/dL
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2 x upper limit of normal (ULN)
• Leukocytes \>= 3,000/mm\^3
• Absolute neutrophils \>= 1,500/mm\^3
• Platelets \>= 100,000/mm\^3
• Patients must have an electrocardiogram (EKG) demonstrating QTc =\< 500 ms within 28 days prior to registration
• Females of child-bearing potential and sexually active males must agree to use effective methods of contraception:
• Child-bearing potential is defined as any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

You may not qualify if:

• Patients who have received topical therapy, systemic chemotherapy, or biological therapy within 4 weeks prior to registration are NOT eligible for participation
• Patients who have undergone major surgery within 21 days prior to registration are NOT eligible for participation
• Patients who have an acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to registration are NOT eligible for participation
• Patients in whom IV fluid hydration is contraindicated (e.g. due to pre-existing pulmonary, cardiac, or renal impairment) will NOT be eligible for participation
• Patients who are pregnant and/or lactating are NOT eligible for participation
• Patients who have had a prior stem cell transplantation are NOT eligible for participation
• Patients who have had any of the following cardiac conditions are NOT eligible for participation (unless otherwise noted):
• Unstable angina or myocardial infarction within 4 months prior to registration
• New York Heart Association (NYHA) class II or IV heart failure
• Uncontrolled angina
• A history of severe coronary artery disease
• Severe, uncontrolled ventricular arrhythmias
• Sick sinus syndrome
• Electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities UNLESS the patient has a pacemaker
• Patients who exhibit uncontrolled hypertension (\>= 140/90 mmHg) or uncontrolled diabetes within 14 days prior to registration are NOT eligible for participation

Sponsors & Collaborators

• Northwestern University: lead
• Amgen: collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Related Publications (1)

• Valipour A, Jager M, Wu P, Schmitt J, Bunch C, Weberschock T. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD008946. doi: 10.1002/14651858.CD008946.pub3.

  PMID: 32632956 DERIVED

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome

Interventions

carfilzomib; romidepsin

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

This study terminated early before accrual was met due to slow accrual.

Results Point of Contact

• Title: Barbara Pro, MD
• Organization: Northwestern University

barbara.pro@nm.org

312-695-6832

Study Officials

• Barbara Pro, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 21, 2012
• First Posted: November 30, 2012
• Study Start: March 22, 2013
• Primary Completion: October 11, 2016
• Study Completion: October 11, 2016
• Last Updated: August 29, 2019
• Results First Posted: August 29, 2019

Record last verified: 2019-04

Locations

US (1)