NCT02281279

Brief Summary

This phase I/II trial studies the side effects and best dose of romidepsin and lenalidomide when combined with rituximab and to see how well this combination works in treating patients with B-cell non-Hodgkin lymphoma that has returned (recurrent) or did not respond to treatment (refractory). Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Romidepsin and lenalidomide may stop the growth of cancer cells by blocking enzymes needed for cell growth. Giving rituximab together with romidepsin and lenalidomide may be a better treatment for B-cell non-Hodgkin lymphoma.

Trial Health

10
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Status
withdrawn

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Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 30, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

November 3, 2014

Completed
1.9 years until next milestone

Study Start

First participant enrolled

October 1, 2016

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2020

Completed
Last Updated

August 11, 2016

Status Verified

August 1, 2016

Enrollment Period

4 years

First QC Date

October 30, 2014

Last Update Submit

August 9, 2016

Conditions

B-cell Adult Acute Lymphoblastic LeukemiaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueIntraocular LymphomaNodal Marginal Zone B-cell LymphomaRecurrent Adult Acute Lymphoblastic LeukemiaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Grade III Lymphomatoid GranulomatosisRecurrent Adult Immunoblastic Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Small Lymphocytic LymphomaRefractory Hairy Cell LeukemiaSmall Intestine LymphomaSplenic Marginal Zone LymphomaTesticular LymphomaWaldenström Macroglobulinemia

Outcome Measures

Primary Outcomes (2)

  • MTD, defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I)

    28 days

  • Overall response rate (Phase II)

    A success is defined as a CR or partial response (PR) noted as the objective status. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.

    Up to 5 years

Secondary Outcomes (7)

  • Adverse events profile, graded according to the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)

    Up to 30 days post-treatment

  • Toxicity profile, defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment (Phase I)

    Up to 30 days post-treatment

  • Response profile, defined to be a CR or PR noted as the objective status (Phase I)

    Up to 5 years

  • CR rate (Phase II)

    Up to 5 years

  • Survival time (Phase II)

    Time from registration to death due to any cause, assessed up to 5 years

  • +2 more secondary outcomes

Other Outcomes (1)

  • BCL-2 sequence

    Baseline

Study Arms (1)

Treatment (rituximab, romidepsin, lenalidomide)

EXPERIMENTAL

Patients receive rituximab IV over 90 minutes on day 1; romidepsin IV over 4 hours on either day 1, days 1 and 8, or days 1, 8, and 15; and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Biological: rituximabDrug: lenalidomideDrug: romidepsinOther: laboratory biomarker analysis

Interventions

rituximabBIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Treatment (rituximab, romidepsin, lenalidomide)
lenalidomideDRUG

Given PO

Also known as: CC-5013, IMiD-1, Revlimid
Treatment (rituximab, romidepsin, lenalidomide)
romidepsinDRUG

Given IV

Also known as: FK228, FR901228, Istodax
Treatment (rituximab, romidepsin, lenalidomide)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (rituximab, romidepsin, lenalidomide)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • PHASE I: Histological confirmation of relapsed (recurrent after previous therapy\[ies\]) or refractory (no response to previous therapy\[ies\]) B-cell NHL; note: patients with small lymphocytic lymphoma (SLL) are eligible however patients with chronic lymphocytic leukemia (CLL) are not eligible
  • PHASE II: Histological confirmation of transformation of FL lymphoma to diffuse large B cell lymphoma or aggressive lymphoma
  • The biopsy confirming diagnosis can be up to 12 weeks prior to registration as long as there is no intervening therapy; note: if patient has had lymphoma treatment since previous biopsy, a biopsy should be repeated
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Measurable disease (at least 1 lesion of \>= 1.5 cm in diameter) as detected by computed tomography (CT) or the CT images of the positron emission tomography (PET)/CT
  • Absolute neutrophil count (ANC) \>= 1500/mm\^3
  • Platelet count \>= 75,000/mm\^3
  • Total bilirubin =\< 1.5 x upper limit of normal (ULN) or if total bilirubin is \> 1.5 x ULN, the direct bilirubin =\< ULN
  • Alkaline phosphatase =\< 3 x ULN unless due to direct lymphoma involvement, and then =\< 5 x ULN
  • Aspartate transaminase (AST) =\< 3 x ULN unless due to direct lymphoma involvement, and then =\< 5x ULN
  • Calculated creatinine clearance \>= 50 mL/min using the Cockcroft-Gault formula
  • Magnesium \>= 1.6 mg/dL
  • Potassium \>= 3.5 mg/dL
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid Risk Evaluation and Mitigation Strategy (REMS)® program
  • Willing to be registered into the mandatory Revlimid REMS® program, and willing and able to comply with the requirements of the REMS® program
  • +7 more criteria

You may not qualify if:

  • Prior therapy with histone deacetylase (HDAC) inhibitors or immunomodulatory drugs (IMDs) (lenalidomide or thalidomide)
  • Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Active central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells that requires therapy
  • Prolongation of corrected QT interval of \> 480 ms
  • Receiving any medications that prolong the corrected QT (QTc) and have a known risk for Torsades de pointes; note: providers should use caution with drugs with possible increased risk for Torsades de pointes; patient will be eligible if they can be taken off these medications prior to initiation of therapy and no less than 4 half-life of the medication
  • Receiving any medications or substances that are strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5)
  • Use of the following strong inhibitors are prohibited =\< 7 days prior to registration
  • Boceprevir (Victrelis™)
  • Clarithromycin (Biaxin®, Biaxin XL®)
  • Conivaptan (Vaprisol®)
  • Grapefruit juice
  • Indinavir (Crixivan®)
  • +32 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Intraocular LymphomaLymphoma, B-Cell, Marginal ZonePrecursor Cell Lymphoblastic Leukemia-LymphomaBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticLymphoma, FollicularLymphoma, Mantle-CellLeukemia, Lymphocytic, Chronic, B-CellLeukemia, Hairy CellWaldenstrom Macroglobulinemia

Interventions

RituximabLenalidomideromidepsin

Condition Hierarchy (Ancestors)

LymphomaNeoplasms by Histologic TypeNeoplasmsEye NeoplasmsNeoplasms by SiteLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphoma, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsPhthalimidesPhthalic AcidsAcids, CarbocyclicCarboxylic AcidsOrganic ChemicalsPiperidonesPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Grzegorz Nowakowski

    Mayo Clinic

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 30, 2014

First Posted

November 3, 2014

Study Start

October 1, 2016

Primary Completion

October 1, 2020

Last Updated

August 11, 2016

Record last verified: 2016-08