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

NCT00764517 | Completed Phase 2 Results DMC

• 6 other identifiers: IRB00004180NCI-2011-037374180HEM-08002-LCR00021415P30CA069533
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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.

  2 years

• 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.

  6 months

• 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.

  6 months

Secondary Outcomes (4)

• Progression-free Survival

  Up to 5 years

• Event-free Survival

  Up to 5 years

• Contribution (if Any) of DNA Methylation/Histone Deacetylation

  Up to 2 years

• Scientific Correlates

  Baseline

Study Arms (2)

Previously untreated

EXPERIMENTAL

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.

Drug: Cladribine; Other: Laboratory Biomarker Analysis; Biological: Rituximab; Drug: Vorinostat

Relapsed

EXPERIMENTAL

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.

Drug: Cladribine; Other: Laboratory Biomarker Analysis; Biological: Rituximab; Drug: Vorinostat

Interventions

Cladribine DRUG

Given IV

Also known as: 2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251

Previously untreated; Relapsed

Laboratory Biomarker Analysis OTHER

Correlative studies

Previously untreated; Relapsed

Rituximab BIOLOGICAL

Given IV

Also known as: 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

Previously untreated; Relapsed

Vorinostat DRUG

Given PO

Also known as: L-001079038, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza

Previously untreated; Relapsed

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Related Publications (1)

• 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.

  PMID: 31177537 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Cladribine; Rituximab; Vorinostat

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Limitations and Caveats

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

Results Point of Contact

• Title: Dr. Stephen E. Spurgeon MD
• Organization: Knight Cancer Institute, Oregon Health & Science University

spurgeos@ohsu.edu

503-494-4606

Study Officials

• Stephen Spurgeon

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 1, 2008
• First Posted: October 2, 2008
• Study Start: August 1, 2008
• Primary Completion: January 1, 2015
• Study Completion: March 1, 2017
• Last Updated: December 11, 2017
• Results First Posted: November 13, 2017

Record last verified: 2017-10

Locations

US (2)