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Recurrent Cutaneous T-cell Non-Hodgkin LymphomaPhase 1NCT01738594

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

A Phase 1 study testing carfilzomib, romidepsin and laboratory biomarker analysis in people with Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma and Recurrent Mycosis Fungoides/Sezary Syndrome, run by Northwestern University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
carfilzomib, romidepsin and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteUnited States
Study dates
22 Mar 2013to 11 Oct 2016
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • 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
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  • 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:
  • Has NOT undergone a hysterectomy or bilateral oophorectomy; OR
  • Has NOT been naturally menopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months)
  • The effectiveness of hormonal contraceptives may be reduced by romidepsin, thus effective methods should include at least 1 form of barrier contraception
  • Females of child-bearing potential must have a negative pregnancy test within 7 days prior to registration
  • Patients must be disease free of any prior malignancies for >= 3 years
  • The exception to this would be currently treated squamous cell and basal cell carcinoma of the skin, carcinoma in situ of the cervix, breast, or bladder, or surgically removed melanoma in situ of the skin (stage 0) with histologically confirmed free margins of excision
  • Patients must give written informed consent prior to registration on the study

Who cannot join

  • 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
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  • 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
  • Patients who have experienced significant neuropathy (grades 3-4 or grade 2 with pain) within 14 days prior to registration are NOT eligible for participation
  • Patients who have a known history of allergy to Captisol (a cyclodextrin derivative used to stabilize carfilzomib) are NOT eligible for participation
  • Patients who have a contraindication to any of the required concomitant drugs or supportive treatments (including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment) are NOT eligible for participation
  • Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to registration are NOT eligible for participation
  • Patients who have any serious condition, laboratory abnormality, or psychiatric illness that would prevent them from singing the informed consent form are NOT eligible for participation
  • Patients who have had prior exposure to romidepsin or any proteasome inhibitor are NOT eligible for participation
  • Patients with a known human immunodeficiency virus (HIV) infection are NOT eligible for participation
  • Patients who test positive for infectious hepatitis types A, B, or C within 14 days of registration are NOT eligible for participation

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Northwestern University

    Chicago, Illinois, 60611

Other trials in United States

About this study

Official title: A Randomized Phase I Dose-Escalation Trial of Carfilzomib With and Without Romidepsin in Cutaneous T-Cell Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of carfilzomib, both as a single agent as well as in combination with romidepsin, in patients with cutaneous T-cell lymphoma (CTCL).

SECONDARY OBJECTIVES:

  1. Overall response rate (ORR). II. Duration of response. III. Time to progression (TTP).

TERTIARY OBJECTIVES:

  1. Measure proteasome activity concurrently in peripheral blood mononuclear cells (PBMCs) and tumor tissue biopsy specimens in order to gather pilot data on proteasome inhibition in CTCL patients treated with carfilzomib alone as well as carfilzomib with romidepsin.

OUTLINE: This is a dose-escalation study of carfilzomib. Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive carfilzomib intravenously (IV) over 30 minutes on days 1, 2, 8, 9, 15, and 16.

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

In both arms, treatment repeats every 28 days for at least 2-4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 1 year.

Being tested
carfilzomib, romidepsin, laboratory biomarker analysis
Medical subject headings
Lymphoma, T-Cell, Cutaneous, Mycosis Fungoides, Sezary Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • carfilzomibDrug

    Also called Kyprolis, PR-171

    Given IV

  • romidepsinDrug

    Also called FK228, FR901228, Istodax

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01738594
Study groupRoleWhat they receive
Arm A (carfilzomib)ExperimentalPatients receive carfilzomib IV over 2-10 minutes on days 1, 2, 8, 9, 15, and 16.
Receives: Drug: carfilzomib; Other: laboratory biomarker analysis
Arm B (carfilzomib, romidepsin)ExperimentalPatients receive carfilzomib as in Arm A and romidepsin IV over 4 hours on days 1, 8, and 15.
Receives: Drug: carfilzomib; Drug: romidepsin; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

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

Secondary outcomes (3)
  1. Overall Response Rate (ORR) of the Disease When Treated With Carfilzomib Alone and When Taken With Romidepsin

    Overall Response Rate (ORR) is defined as number of patients who's best response is complete response or partial response. Response will be categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). The overall response rate of the study treatment will be evaluated based on skin biopsy, CT scans, and blood tests at the beginning of the study as well as every 56 days (2 cycles).

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

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

    Duration of response will be defined as the time from the point at which response is achieved until the point of disease progression. The duration of response of the study treatment will be evaluated based on skin biopsy, CT scans, and blood tests at the beginning of the study as well as every 56 days (2 cycles).

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

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

    The time to progression (TTP) will be measured as the time from the first dose of study therapy until the point at which disease is determined to have progressed or patients discontinue therapy for toxicity. To measure time to progression, the study treatment will be evaluated based on skin biopsy, CT scans, and blood tests at the beginning of the study as well as every 56 days (2 cycles).

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Nov 2012 (estimated)
  2. Study start22 Mar 2013
  3. Primary completion11 Oct 2016
  4. Study completion11 Oct 2016

Why it stopped: Slow accrual

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01738594
Sponsor's protocol ID
NU 12H06
Other IDs
STU00071042, NCI-2012-01952
Status last verified
Apr 2019
First submitted
21 Nov 2012
Last updated
29 Aug 2019
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 32632956

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing carfilzomib, romidepsin and laboratory biomarker analysis in people with Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma and Recurrent Mycosis Fungoides/Sezary Syndrome, run by Northwestern University 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 22 inclusion and 23 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: stopped early, as of the sponsor's last update on 29 Aug 2019. 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?

Yes. Results are posted in the registry (first posted 29 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Patients With Dose Limiting Toxicities (DLTs) (time frame: During the first 28 days (1 cycle=28 days) of treatment.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01738594, which also lists 1 linked publication.

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 29 Aug 2019.

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