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Recurrent Grade 1 Follicular LymphomaPhase 2NCT00079443

FR901228 Alone or Combined With Rituximab and Fludarabine in Treating Patients With Relapsed or Refractory Low-Grade B-Cell Non-Hodgkin's Lymphoma

A Phase 2 study testing romidepsin, rituximab and fludarabine phosphate in people with Recurrent Grade 1 Follicular Lymphoma and Recurrent Grade 2 Follicular Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
romidepsin, rituximab and fludarabine phosphate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteUnited States
Study dates
Jan 2004to Sep 2005
Phase
Phase 2
Are there results?
None posted in the registry

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 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Maryland Greenebaum Cancer Center

    Baltimore, Maryland, 21201-1595

Other trials in United States

About this study

Official title: A Phase II Study of Single Agent Depsipeptide (NSC 630176) Followed by a Phase I Study of Rituximab/Fludarabine Combination With an Escalating Dose of Depsipeptide in Relapsed or Refractory Low Grade B Cell Lymphomas

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. For phase 2: is to assess the clinical efficacy (complete and partial response rates) of single agent depsipeptide.

II. For phase 1: is to assess the feasibility of adding Depsipeptide to a regimen of Rituximab and Fludarabine and to establish the MTD of Depsipeptide in this combination.

SECONDARY OBJECTIVES:

  1. To correlate disease response (clinical outcome) with the changes in histone acetylation assays.

II. Study the expression of death receptors of DR4 and DR5 after treatment with depsipeptide.

III. Assessment of minimal residual disease by immune histochemistry.

OUTLINE: This is a multicenter, phase II study of single-agent FR901228 followed by a phase I, dose-escalation study of FR901228.

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.

Cohorts of 3-6 patients receive escalating doses of FR901228 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed for up to 3 years from study entry.

Being tested
romidepsin, rituximab, fludarabine phosphate, laboratory biomarker analysis
Medical subject headings
Lymphoma, Follicular, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

  • romidepsinDrug

    Also called FK228, FR901228, Istodax

    Given IV

  • rituximabBiological

    Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8

    Given IV

  • fludarabine phosphateDrug

    Also called 2-F-ara-AMP, Beneflur, Fludara

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00079443
Study groupRoleWhat they receive
TreatmentExperimentalPHASE 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.
Receives: Drug: romidepsin; Biological: rituximab; Drug: fludarabine phosphate; Other: laboratory biomarker analysis

What is being measured

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

  1. Objective response rate (Phase II)

    Exact confidence interval of the response rate will be calculated.

    Measured: Up to 3 years

  2. Survival (Phase II)

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

    Measured: Up to 3 years

  3. 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)

    Measured: Up to 28 days

Timeline

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

  1. First posted10 Mar 2004 (estimated)
  2. Study startJan 2004
  3. Primary completionSep 2005

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00079443
Sponsor's protocol ID
NCI-2013-00043
Other IDs
UMGCC #0307, MSGCC-0307, CDR0000355763, NCI-6015, U01CA069854
Status last verified
Jun 2013
First submitted
8 Mar 2004
Last updated
1 Jul 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing romidepsin, rituximab and fludarabine phosphate in people with Recurrent Grade 1 Follicular Lymphoma and Recurrent Grade 2 Follicular Lymphoma, run by National Cancer Institute (NCI) at 1 site 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 14 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: stopped early, as of the sponsor's last update on 1 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

The study was stopped early. Results are not available in the source record.

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 (Phase II) (time frame: Up to 3 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 NCT00079443.

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 1 Jul 2013.

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