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Adult Nasal Type Extranodal NK/T-cell LymphomaPhase 1NCT01129180

Bortezomib and Azacitidine in Treating Patients With Relapsed or Refractory T-Cell Lymphoma

A Phase 1 study testing azacitidine, bortezomib and Correlative studies in people with Adult Nasal Type Extranodal NK/T-cell Lymphoma and Anaplastic Large Cell Lymphoma, run by Pierluigi Porcu at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Bortezomib and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with azacitidine in treating patients with relapsed or refractory T-cell lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
azacitidine, bortezomib and Correlative studies
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
May 2010to Dec 2012
Phase
Phase 1
Are there results?
None posted in the registry

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 pathologically documented T-cell lymphoma belonging to one of the following WHO entities: Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS); Mycosis Fungoides and Sezary Syndrome (MF-SS); Angioimmunoblastic T-cell lymphoma (AITL); CD30-positive Anaplastic Large Cell Lymphoma (ALCL), systemic; T/NK-cell lymphoma, extranodal, nasal and nasal type; Hepatosplenic T-cell lymphoma, gamma/delta or alpha/beta; Enteropathy-associated T-cell lymphoma (EATL); Adult T-cell Leukemia/Lymphoma (ATLL); Subcutaneous panniculitis-like T-cell lymphoma (SCPTCL); Blastic T/NK-cell lymphoma/leukemia (CD4+CD56+ Hematodermic Tumor); T/NK-cell post-transplant lymphoproliferative disorders (PTLD); Large Granular Lymphocyte (LGL) Leukemia; T-cell Prolymphocytic Leukemia (T-PLL)
  • Patients must have relapsed or refractory TCL
  • Patients must have failed at least one prior systemic therapy
  • Life expectancy must be greater than 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Patients must have adequate organ function as defined below:
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  • Total bilirubin < 1.5 x upper limit of normal (ULN)
  • AST(aspartate aminotransferase) < 2.0 x ULN
  • ALT(Alanine transaminase) < 2.0 x ULN
  • Serum creatinine < 1.5 ULN
  • New York Heart Association Congestive Heart Failure (NYHA CHF) Class II or better
  • Platelet count >= 75,000/mm^3 (unless due to disease) within 14 days before enrollment
  • Absolute neutrophil count of >= 1,500/mm^3 within 14 days before enrollment
  • Women of childbearing potential must have a negative serum pregnancy test prior to azacitidine treatment; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; if the patient does not agree, the patient is not eligible; women must agree to not get pregnant for the duration of the study; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform the PI or the Study Nurse immediately
  • Ability to understand and willingness to sign the written informed consent document before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
  • Male subject agrees to use an acceptable method for contraception for the duration of the study

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
  • Patients receiving any other investigational agents or patients who have received other investigational agents within 14 days of enrollment
  • Patients with active central nervous system (CNS) malignancy
  • Patients with history of allergic reactions attributed to compounds of similar chemical or biologic composition to Azacitidine or VELCADE (BORTEZOMIB) that are not easily managed; patients with hypersensitivity to VELCADE (BORTEZOMIB), boron, or mannitol
  • Patients must not have previously received Azacitidine or VELCADE (BORTEZOMIB) for any disease
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; as infection is a common feature of TCL, patients with active infection are permitted to enroll provided that the infection is under control; myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant
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  • Pregnant women or women who are breastfeeding are excluded from this study; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
  • HIV-positive patients are ineligible; all patients will be screened for HIV
  • Patients with pre-existing Grade 2 or higher neuropathy within 14 days before enrollment or other serious neurologic toxicity that would significantly increase risk of complications from VELCADE (BORTEZOMIB) therapy are excluded
  • Patients with active, advanced malignant solid tumors are excluded
  • Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: Phase I Dose-Escalation Study of Azacitidine (Vidaza) and Bortezomib (Velcade) in T-Cell Lymphoma

RATIONALE: Bortezomib and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with azacitidine in treating patients with relapsed or refractory T-cell lymphoma.

Read the detailed description

PRIMARY OBJECTIVES I. To determine the maximum tolerated dose (MTD) of VELCADE (BORTEZOMIB) in combination with Azacitidine in patients with relapsed/refractory CTCL/PTCL.

II. To define the specific toxicities and the dose-limiting toxicity (DLT) of VELCADE (BORTEZOMIB) in combination with Azacitidine.

SECONDARY OBJECTIVES I. To determine the overall response rate (ORR). II. To correlate the biological activity of Azacitidine as a demethylating agent (changes in target gene methylation and gene expression, DNMT1 protein expression, global methylation) with clinical endpoints and plasma pharmacokinetics of Azacitidine.

III. To characterize the biological activity of VELCADE (BORTEZOMIB) as a potential demethylating agent.

IV. To correlate intracellular concentration of Azacitidine-triphosphate with global DNA methylation and other biological endpoints as well as clinical response.

  1. To explore the biologic role of microRNAs in determining clinical response to the VELCADE (BORTEZOMIB) plus Azacitidine combination and achievement of the other pharmacodynamic endpoints.

OUTLINE: This is a dose-escalation study of bortezomib.

Patients receive bortezomib IV on days 4, 8, 11, and 15 and azacitidine subcutaneously (SC) on days 1-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment patients are followed up for at least 30 days.

Being tested
azacitidine, bortezomib, Correlative studies
Keywords
T-Cell Lymphoma
Medical subject headings
Lymphoma, Extranodal NK-T-Cell, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Lymphoma, T-Cell, Peripheral, Leukemia, Prolymphocytic, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, T-Cell, Cutaneous, Mycosis Fungoides

What participants receive

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

  • azacitidineDrug

    Also called 5-AC, 5-azacytidine, 5-AZC, azacytidine

    Given SC

  • bortezomibDrug

    Also called LDP 341, MLN341, PS-341, VELCADE

    Given IV

  • Correlative studiesProcedure or surgery

    Also called PK, PD, pharmacodynamic, pharmacokinectic

    Correlative studies will be collected pre-treatment, day 4 , day 15, day 29(pre-cycle 2)

Study groups in NCT01129180
Study groupRoleWhat they receive
Arm IExperimentalPatients receive bortezomib IV on days 4, 8, 11, and 15 and azacitidine SC on days 1-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Attempt to collect Correlative studies will be made.
Receives: Drug: azacitidine; Drug: bortezomib; Procedure: Correlative studies

What is being measured

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

  1. Maximum tolerable dose (MTD) of bortezomib in combination with azacitidine

    Measured: up to 28 days

  2. Specific toxicities and the dose limiting toxicity (DLT) of bortezomib in combination with azacitidine as assessed by NCI CTCAE (Common Toxicity Criteria for Adverse Effects) v4.0

    Measured: up to 2 years

Secondary outcomes (5)

  1. Overall response rate

    Measured: up to 2 years

  2. Correlation of the biological activity of Azacitidine as a demethylating agent with clinical endpoints and plasma pharmacokinetics

    Measured: up to 2 years

  3. Biological activity of bortezomib as a potential demethylating agent

    Measured: up to 2 years

  4. Correlation of intracellular concentration of azacitidine-triphosphate with global DNA methylation and other biological endpoints as well as clinical response

    Measured: up to 2 years

  5. Biologic role of microRNAs in determining clinical response to the bortezomib plus azacitidine combination and achievement of the other pharmacodynamic endpoints

    Measured: up to 2 years

Timeline

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

  1. First posted24 May 2010 (estimated)
  2. Study startMay 2010
  3. Primary completionMay 2012
  4. Study completionDec 2012

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01129180
Sponsor's protocol ID
OSU-08067
Other IDs
NCI-2010-01081
Status last verified
Dec 2013
First submitted
17 May 2010
Last updated
3 Dec 2013
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing azacitidine, bortezomib and Correlative studies in people with Adult Nasal Type Extranodal NK/T-cell Lymphoma and Anaplastic Large Cell Lymphoma, run by Pierluigi Porcu 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 16 inclusion and 12 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: finished, as of the sponsor's last update on 3 Dec 2013. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum tolerable dose (MTD) of bortezomib in combination with azacitidine (time frame: up to 28 days). The study lists 2 primary outcomes in all. 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 NCT01129180.

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 3 Dec 2013.

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