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Recurrent B-Cell Non-Hodgkin LymphomaPhase 2NCT00764517

Vorinostat, Cladribine, and Rituximab in Treating Patients With Mantle Cell Lymphoma, Relapsed Chronic Lymphocytic Leukemia, or Relapsed B Cell Non-Hodgkin's Lymphoma

A Phase 2 study testing Cladribine, Laboratory Biomarker Analysis and Rituximab in people with Recurrent B-Cell Non-Hodgkin Lymphoma and Recurrent Chronic Lymphocytic Leukemia, run by OHSU Knight Cancer Institute at 2 sites 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

This phase II trial studies how well giving vorinostat, cladribine, and rituximab together works in treating patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), or B cell non-Hodgkin's lymphoma (NHL) that has returned after a period of improvement. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cladribine, Laboratory Biomarker Analysis and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
57 participants
Where
2 sitesUnited States
Study dates
Aug 2008to Mar 2017
Phase
Phase 2
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 be able to provide informed consent according to institutional guidelines
  • Patients must have: 1) MCL; or 2) relapsed or refractory cluster of differentiation (CD)20 positive B-cell indolent NHL; or 3) relapsed CLL
  • Patients must have measurable disease/disease status requirements as follows:
  • For CLL patients, symptomatic disease as defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria that mandate treatment
  • For B-cell NHL patients must have at least one of the following to be eligible:
  • Positron emission tomography (PET) avid or measurable disease by computed tomography (CT) scan defined as at least 1 lesion that measures > 2 cm in a single dimension
Show all 16Show fewer
  • Significant bone marrow and/or peripheral blood involvement by NHL (i.e. leukemic phase) as determined by the investigator
  • Patients with Waldenström macroglobulinemia (WM) are exempt from this requirement if they have symptomatic hyperviscosity or clinically relevant cytopenias and elevated serum immunoglobulin M (IgM)
  • Patients must have adequate bone marrow reserve as indicated by an absolute neutrophil count (ANC) > 1.500/mm^3 and platelet count > 150.000/mm^3 if no bone marrow involvement; however, if there is significant lymphoma/leukemia bone marrow infiltration, no pre-existing hematologic parameters must be met
  • Patients must have a performance status of 0, 1, or 2 according to Eastern Cooperative Oncology Group
  • Serum creatinine < 2.0 mg/dL or estimated glomerular filtration rate (GFR) > 60 mL/min
  • Serum bilirubin =< 1.5 × upper limit of normal (ULN)
  • Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 × ULN
  • Alkaline phosphatase =< 2.5 × ULN
  • Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment
  • Male and female patients must agree to use an effective contraceptive method during the study and for a minimum of 6 months after study treatment

Who cannot join

  • Significant hypersensitivity to cladribine or vorinostat; hypersensitivity to rituximab infusion is not an exclusion criterion; however, appropriate changes to infusion schedules will be made based on current or prior reactions
  • Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol
  • Patients with a diagnosis of a relapsed/refractory aggressive cluster of differentiation antigen 20 (CD20)+ B-cell neoplasm defined as Burkitt's lymphoma or diffuse large B-cell lymphoma
  • A diagnosis of acute lymphoplasmic leukemia, and lymphoblastic lymphoma
  • Use of investigational agents or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea and steroids; the patient must have recovered from all acute toxicities from any previous therapy
  • Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment
Show all 12Show fewer
  • Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
  • Pregnant or lactating patients
  • Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
  • Patients with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) associated complex are not eligible for treatment
  • Patients with active hepatitis B or C are not eligible for the study
  • Patients taking other histone deacetylases (HDAC) inhibitors; for example, patients taking valproic acid, there must be a 14 day washout period prior to enrollment in this study

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: Phase II Study of Vorinostat (SAHA), Cladribine, and Rituximab (SCR) in Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia, and Relapsed B Cell Non-Hodgkin Lymphoma

This phase II trial studies how well giving vorinostat, cladribine, and rituximab together works in treating patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), or B cell non-Hodgkin's lymphoma (NHL) that has returned after a period of improvement. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cladribine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Giving vorinostat together with cladribine and rituximab may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine objective response rates of the SCR regimen (vorinostat, cladribine, and rituximab) in B-cell malignancies.

II. Determine the tolerability and toxicities of the SCR regimen.

SECONDARY OBJECTIVES:

  1. Evaluate progression free survival in patients treated with SCR. II. Estimate event free survival for patients treated with SCR. III. Determine the contribution (if any) of deoxyribonucleic acid (DNA) methylation/histone deacetylation to disease progression and/or response to SCR combination chemotherapy.

IV. Perform scientific correlates to determine if SCR treatment a) is associated with global and gene specific changes in transcription of messenger ribonucleic acid (mRNA)s and micro ribonucleic acid (MiRNA)s b) is acting as an inhibitor of DNA methylation c) is activating or silencing specific genes or miRNAs.

OUTLINE:

Patients receive vorinostat orally (PO) on days 1-14, cladribine intravenously (IV) over 2 hours on days 1-5, and rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years and then every 6 months thereafter.

Being tested
Cladribine, Laboratory Biomarker Analysis, Rituximab, Vorinostat
Medical subject headings
Lymphoma, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

  • CladribineDrug

    Also called 2-CdA, 2CDA, CdA, Cladribina

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • RituximabBiological

    Also called BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, IDEC-102

    Given IV

  • VorinostatDrug

    Also called L-001079038, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid

    Given PO

Study groups in NCT00764517
Study groupRoleWhat they receive
Previously untreatedExperimentalPatients enrolled with untreated, newly diagnosed mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) [Group I]. Patients receive vorinostat PO on days 1-14, cladribine IV over 2 hours on days 1-5, and rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cladribine; Other: Laboratory Biomarker Analysis; Biological: Rituximab; Drug: Vorinostat
RelapsedExperimentalPatients with relapsed disease including indolent Non-Hodgkins Lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) [Group II]. Patients receive vorinostat PO on days 1-14, cladribine IV over 2 hours on days 1-5, and rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cladribine; Other: Laboratory Biomarker Analysis; Biological: Rituximab; Drug: Vorinostat

What is being measured

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

  1. Objective Response Rate

    ORR defined as the percentage of patients who achieved a complete response (CR) or a partial response (PR). Assessed per the revised Cheson criteria. Response definitions per revised International Working Group Response Criteria. 95% confidence interval will be provided. Definitions: Complete response (CR) = disappearance of all evidence of disease; Partial response (PR) = regression of measurable disease and no new sites.

    Measured: 2 years

  2. Toxicities as Assessed Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

    Toxicity is determined percentage of patients that experienced an adverse event (AE) grade 3 or higher during the time frame, assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade refers to the severity of the AE increasing from Grade 1 to 5. Generally, Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences; Grade 5 = Death related to AE.

    Measured: 6 months

  3. Tolerability of Treatment

    Tolerability is determined to be the percentage of patients who completed the full duration of treatment (all 6 cycles) regardless of adverse event status. % tolerability shows the rate of patients that tolerated the treatment for the full duration.

    Measured: 6 months

Secondary outcomes (4)

  1. Progression-free Survival

    Time from treatment start until disease progression or death.

    Estimated using the Kaplan-Meier method. A logrank test will be used to compare progression-free survival between Group I and Group II. A p-value less that 0.05 will be considered statistically significant.

    Measured: Up to 5 years

  2. Event-free Survival

    Time from treatment start until disease progression, death, or discontinuation of treatment for adverse event (toxicity)

    Estimated using the Kaplan-Meier method. A logrank test will be used to compare progression-free survival between Group I and Group II. A p-value less that 0.05 will be considered statistically significant.

    Measured: Up to 5 years

  3. Contribution (if Any) of DNA Methylation/Histone Deacetylation

    Determine the contribution (if any) of DNA methylation/histone deacetylation to disease progression and/or response to SCR combination chemotherapy.

    Outcome not evaluated due to technical challenges collecting the data, and lack of budget and personnel to complete the analysis.

    Measured: Up to 2 years

  4. Scientific Correlates

    Perform scientific correlates to determine if SCR treatment a) is associated with global and gene specific changes in transcription of mRNAs and MiRNAs b) is acting as an inhibitor of DNA methylation c) is activating or silencing specific genes or miRNAs.

    Outcome not evaluated due to technical challenges collecting the data, and lack of budget and personnel to complete the analysis.

    Measured: Baseline

Timeline

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

  1. First posted2 Oct 2008 (estimated)
  2. Study startAug 2008
  3. Primary completionJan 2015
  4. Study completionMar 2017

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00764517
Sponsor's protocol ID
IRB00004180
Other IDs
NCI-2011-03737, 4180, HEM-08002-L, CR00021415, IRB00004180, P30CA069533
Status last verified
Oct 2017
First submitted
1 Oct 2008
Last updated
11 Dec 2017
Data monitoring committee
Yes

Publications

  • Spurgeon SE, Sharma K, Claxton DF, Ehmann C, Pu J, Shimko S, Stewart A, Subbiah N, Palmbach G, LeBlanc F, Latour E, Chen Y, Mori M, Hasanali Z, Epner EM. Phase 1-2 study of vorinostat (SAHA), cladribine and rituximab (SCR) in relapsed B-cell non-Hodgkin lymphoma and previously untreated mantle cell lymphoma. Br J Haematol. 2019 Sep;186(6):845-854. doi: 10.1111/bjh.16008. Epub 2019 Jun 9.

    PubMed 31177537

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cladribine, Laboratory Biomarker Analysis and Rituximab in people with Recurrent B-Cell Non-Hodgkin Lymphoma and Recurrent Chronic Lymphocytic Leukemia, run by OHSU Knight Cancer Institute at 2 sites 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 11 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 13 Nov 2017). 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?

Objective Response Rate (time frame: 2 years). The study lists 3 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 NCT00764517, 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 11 Dec 2017.

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