NCT00079443

Brief Summary

This phase I/II trial is studying the best dose of FR901228 when given together with rituximab and fludarabine and to see how well FR901228 works alone in treating patients with relapsed or refractory low-grade B-cell non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as FR901228 and fludarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Rituximab may increase the effectiveness of chemotherapy drugs by making cancer cells more sensitive to the drugs.

Trial Health

35
At Risk

Trial Health Score

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

Enrollment
60

participants targeted

Target at P50-P75 for phase_2

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2004

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

March 8, 2004

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 10, 2004

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2005

Completed
Last Updated

July 1, 2013

Status Verified

June 1, 2013

Enrollment Period

1.7 years

First QC Date

March 8, 2004

Last Update Submit

June 28, 2013

Conditions

Recurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (3)

  • Objective response rate (Phase II)

    Exact confidence interval of the response rate will be calculated.

    Up to 3 years

  • Survival (Phase II)

    Kaplan-Meier analysis will be used to describe patient survival.

    Up to 3 years

  • MTD, defined as the highest dose level at which 6 patients have been treated with not more than 1 DLT, graded according to NCI CTC version 2 (Phase I)

    Up to 28 days

Study Arms (1)

Treatment

EXPERIMENTAL

PHASE II: Patients receive FR901228 IV over 4 hours on days 1, 8, and 15. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete or partial remission receive 2 additional courses (for a total of 6 courses). Patients with stable disease after 4 courses or progressive disease at any time after 2 courses proceed to the phase I portion of the study. PHASE I: Patients receive rituximab IV over approximately 4-8 hours on day 1; fludarabine IV over 10-30 minutes on days 2-4; and FR901228 IV over 4 hours on days 2, 9, and 16. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: romidepsinBiological: rituximabDrug: fludarabine phosphateOther: laboratory biomarker analysis

Interventions

romidepsinDRUG

Given IV

Also known as: FK228, FR901228, Istodax
Treatment
rituximabBIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Treatment
fludarabine phosphateDRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara
Treatment
laboratory biomarker analysisOTHER

Correlative studies

Treatment

Eligibility Criteria

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

You may qualify if:

  • Patients must have histologically and clinically confirmed relapsed and/or refractory low grade follicular B cell NHL (follicular small cleaved cell, follicular mixed small and large cell, and small lymphocytic lymphoma (according to the IWF classification); the malignant tissues must be positive for CD 20 on immunohistochemistry or flow cytometry
  • History of one or multiple prior chemotherapy regimens for low grade follicular NHL, but no more than 4 therapies
  • For the phase II trial: previous therapies can include rituximab, fludarabine (alone not in combination or sequentially); the most recent therapy should be completed more then 4 weeks prior to protocol entry, 6 months if the last regimen included Fludarabine, rituximab, nitrosoureas or mitomycin, and at least 8 weeks out from a treatment with UCN-01
  • For phase I trial: Patients can move from phase II to phase I trial if they have not received rituximab and fludarabine in combination or sequentially in the past, if they received one or both agents individually and had a 50% responses; this response corresponds to PR to prior therapy
  • Presence of measurable disease by CT scan 4 weeks after the last chemotherapeutic regimen with at least one lesion greater than 1.5c m in one dimension and or positive bone marrow biopsy
  • ECOG performance status ≤ 2 with a minimal life expectancy of 4 months
  • Female patients of childbearing age should have negative pregnancy test; pregnant and breast-feeding women will not be eligible for the study because the antiproliferative effects of depsipeptide may be harmful to the developing fetus or nursing infants
  • Absolute neutrophil count \>= 1000/µl; lower ANC (\>= 500/µl) count will be considered if they are due to a bone marrow involvement by the disease; patients can receive growth factors (G-CSF and erythropoietin) to sustain the peripheral counts during the cycles of therapy
  • Platelets \>= 100.000/µl; lower platelets (\>50.000/µl) count will be considered if they are due to a bone marrow involvement by the disease; patients can receive growth factors (G-CSF and erythropoietin) to sustain the peripheral counts during the cycles of therapy
  • Total bilirubin =\< 1.5 x institutional upper limit of normal
  • AST/ALT =\< 3 x institutional upper limit of normal
  • Creatinine =\< 1.5 x the institutional upper limit of normal
  • Patients with history of seizures are included if under adequate control; blood levels of seizure medications are monitored during the study
  • The patient must understand the investigational nature of the protocol, potential risks and benefits of the study and provides an informed written consent form

You may not qualify if:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (within 6 weeks for rituximab, nitrosoureas and mitomycin and within 8 weeks for UCN-01) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who had prior treatment with depsipeptide or any other histone deacetylase inhibitor
  • Patients who had prior allogeneic stem cell transplantation
  • Bulky disease: single mass greater than or equal to 10 cm
  • Patients may not be receiving any other investigational agents
  • Patients with known CNS involvement (as documented by MRI and or cerebro-spinal fluid examination) should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse events
  • History of life threatening allergic reactions attributed to agents used in the study
  • Impaired cardiac function: history of life threatening arrhythmias, MI within the preceding 6 months, severe CAD, cardiomyopathy, congestive heart failure \>= NYH II; EF =\< 40%; EKG abnormality i.e.: ischemic ST-T abnormalities, QT prolongation, pathologic q waves, arrhythmias (except for benign PAC's and PVC's, 1st degree AV block, 2nd degree AV block Wenkebach); patients with LVH on EKG will be ineligible for this trial
  • Patients with prior malignancies other then basal cell carcinomas and cervical intra-epithelial neoplasia
  • Patients (or their partners) unwilling to use contraception
  • Patients who require pharmacological doses of corticosteroids for intercurrent medical conditions
  • Patients who uses concomitant drugs which may cause a prolongation of QTc

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201-1595, United States

Location

MeSH Terms

Conditions

Lymphoma, FollicularLeukemia, Lymphocytic, Chronic, B-Cell

Interventions

romidepsinRituximabfludarabine phosphate

Condition Hierarchy (Ancestors)

Lymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Ashraf Badros

    University of Maryland Greenebaum Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 8, 2004

First Posted

March 10, 2004

Study Start

January 1, 2004

Primary Completion

September 1, 2005

Last Updated

July 1, 2013

Record last verified: 2013-06

Locations

US(1)