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

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

57 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-08-31

Study Completion Date

2017-03-31

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVES:

I. 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:

I. 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.

Conditions

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Recurrent B-Cell Non-Hodgkin Lymphoma Recurrent Chronic Lymphocytic Leukemia Recurrent Indolent Adult Non-Hodgkin Lymphoma Refractory B-Cell Non-Hodgkin Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Previously untreated

Patients 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.

Group Type EXPERIMENTAL

Cladribine

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Rituximab

Intervention Type BIOLOGICAL

Given IV

Vorinostat

Intervention Type DRUG

Given PO

Relapsed

Patients 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.

Group Type EXPERIMENTAL

Cladribine

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Rituximab

Intervention Type BIOLOGICAL

Given IV

Vorinostat

Intervention Type DRUG

Given PO

Interventions

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Cladribine

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Rituximab

Given IV

Intervention Type BIOLOGICAL

Vorinostat

Given PO

Intervention Type DRUG

Other Intervention Names

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2-CdA 2CDA CdA Cladribina Leustat Leustatin Leustatine RWJ-26251 BI 695500 C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody MabThera Monoclonal Antibody IDEC-C2B8 PF-05280586 Rituxan Rituximab Biosimilar BI 695500 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 RTXM83 L-001079038 SAHA Suberanilohydroxamic Acid Suberoylanilide Hydroxamic Acid Zolinza

Eligibility Criteria

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Inclusion Criteria

* 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
* 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

Exclusion Criteria

* 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
* 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Stephen Spurgeon

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Stephen Spurgeon

Role: PRINCIPAL_INVESTIGATOR

OHSU Knight Cancer Institute

Locations

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OHSU Knight Cancer Institute

Portland, Oregon, United States

Site Status

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED

PMID: 31177537 (View on PubMed)