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Refractory Chronic Lymphocytic LeukemiaPhase 1NCT00366418

Lower But More Frequent Dose Rituximab to Treat Chronic Lymphocytic Leukemia

A Phase 1 study testing Rituximab in people with Refractory Chronic Lymphocytic Leukemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will test the safety and effectiveness of using lower-dose rituximab given more frequently for treating chronic lymphocytic leukemia (CLL). Studies have shown that, used once a week for 4 weeks, rituximab was effective in up to 25 percent of patients with CLL. Read more about this study

Who is it for?
Ages 21 to 99 years
Conditions the study is for
Refractory Chronic Lymphocytic Leukemia
What is being tested?
Rituximab
How many people
4 participants
Where
1 siteUnited States
Study dates
10 Aug 2006to 11 Jun 2009
Phase
Phase 1
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 21 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients diagnosed with Chronic Lymphocytic Leukemia
  • Prior therapy with fludarabine or a fludarabine containing regimen
  • CD20 expression on CLL cells
  • Neutrophil count ANC greater than 500/mm(3)
  • Platelet count greater than 30K/mm(3)
  • Age 21-99

Who cannot join

  • Bulky lymphadenopathy, defined as greater than 1 lymph node with greater than 5cm in largest diameter
  • Evidence for transformation into high grade lymphoma (Richter's transformation)
  • ECOG performance 3 or higher
  • Other concurrent anticancer therapies
  • Less than 3 months from last systemic therapy for CLL
  • Less than 6 months from last monoclonal antibody therapy
Show all 13Show fewer
  • More than 10 doses rituximab, within 12 months preceeding protocol enrollment, either as single agent or in a combination chemotherapy regimen
  • Chronic or current clinically significant infection, including HIV positivity or hepatitis C
  • Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient's ability to tolerate protocol therapy
  • History of mucocutaneous reactions (paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis)
  • Known anaphylaxis or IgE mediated hypersensitivity to murine proteins or to any component of this product
  • Inability to self inject the study medication or to have it administered by a third person
  • Inability to understand the investigational nature of the study ability to provide informed consent

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Pilot Study of Fractionated Dose Subcutaneous Rituximab (RTX, Rituxan(Registered Trademark)) in Patients With Refractory or Relapsed Chronic Lymphocytic Leukemia

This study will test the safety and effectiveness of using lower-dose rituximab given more frequently for treating chronic lymphocytic leukemia (CLL). Studies have shown that, used once a week for 4 weeks, rituximab was effective in up to 25 percent of patients with CLL. New evidence shows that using lower and more frequent doses of rituximab can be more effective in destroying leukemia cells and produce a better treatment response.

Patients 21 years of age and older with CLL who have received treatment with fludarabine may be eligible for this study.

Read more

Participants take rituximab for 12 weeks. One dose of the drug is infused through an arm vein over about 30 minutes on either day 1 (the first dose) or day 3 (the second dose). All other doses are given as an injection under the skin. After the first week, patients can choose to do these injections at home. Rituximab will be given 3 times a week for a total of 12 weeks. Other medications are given to reduce the side effects and allergic reactions to the drug. In addition to treatment, patients undergo the following tests and procedures:

Before treatment

  • Medical history, physical examination, electrocardiogram (EKG) and blood tests.
  • Bone marrow and lymph node biopsies (surgical removal of a small tissue sample).
  • Computed tomography (CT) and positron emission tomography (PET) scans. CT uses special x-rays to provide images of the neck, chest, abdomen and pelvis. PET uses a radioactive sugar to identify areas of disease.

During treatment (study weeks 1-12)

  • Medical history and physical examinations at weeks 3, 6 and 12 to evaluate drug side effects, plus weekly telephone checks and interim visits when needed.
  • Blood tests every other week to evaluate blood counts.

Evaluations after treatment (follow-up 3 months to 12 months)

  • Blood tests at follow-up visits at 3, 6, 9 and 12 months after treatment to evaluate blood counts.
  • Bone marrow aspiration and biopsy at 3 months after treatment to examine the effects of rituximab on bone marrow cells.
  • CT scans of the neck, chest, abdomen and pelvis at 3, 6, 9 and 12 months after treatment to evaluate the response to treatment.
Read the detailed description

Rituximab is FDA approved for the treatment of relapsed or refractory low grade or follicular CD20+ B cell non Hodgkin's lymphoma (375 mg/m(2) IV infusion once weekly for 4 or 8 doses). Recently, rituximab (anti CD20) has been introduced to CLL treatment regimens and has become an attractive choice in combination chemotherapy or as single agent treatment. Rituximab has been shown to be effective at lower doses than 375 mg/m(2) when given more frequently.

Several theoretical considerations and supporting laboratory evidence suggest that a fractionated dosing schedule using low-dose rituximab could be more effective than the current i.v. schedule of high-dose rituximab. Indeed, preliminary clinical evidence suggests that low-dose rituximab at 20mg/m2 i.v. 3-times per week can lead to steady clearance of leukemic cells without inducing substantial loss of targeted CD20.

This is a Phase I/II , single agent study which will evaluate the safety and feasibility of subcutaneous rituximab (Rituxan) administered at 20 mg/day three times a week for 12 weeks in subjects with CLL. Patients need to have had prior treatment with fludarabine, and have an elevated absolute lymphocyte count. The primary objective will be to test the safety and feasibility of giving rituximab subcutaneously. We will also obtain as a secondary endpoint an early estimate of efficacy as evidenced by (a) shrinkage of lymphadenopathy and/or (b) improvement in blood values and bone marrow biopsy findings.

Being tested
Rituximab
Keywords
CLL, Monoclonal Antibody Therapy, Anti CD20, Biologic Response Modifier Therapy, Fractionated-Dose, Low-Dose, Chronic Lymphocytic Leukemia
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

What is being measured

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

  1. Safety profile and early evidence of efficacy of Rituxan given subcutaneously.

    Measured: 12 weeks

Secondary outcomes (1)

  1. Measurement/deposition of serum compliment components, analysis of rituxan induced gene and protein expression in CLL cells, analysis and binding of rituximab to CLL cells.

    Measured: 1-12 weeks

Timeline

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

  1. First posted21 Aug 2006 (estimated)
  2. Study start10 Aug 2006
  3. Primary completion11 Jun 2009
  4. Study completion11 Jun 2009

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00366418
Sponsor's protocol ID
060228
Other IDs
06-H-0228
Status last verified
23 Feb 2011
First submitted
17 Aug 2006
Last updated
2 Jul 2017
Results posted
No

Publications

  • Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med. 2005 Feb 24;352(8):804-15. doi: 10.1056/NEJMra041720. No abstract available.

    PubMed 15728813

  • Beum PV, Kennedy AD, Williams ME, Lindorfer MA, Taylor RP. The shaving reaction: rituximab/CD20 complexes are removed from mantle cell lymphoma and chronic lymphocytic leukemia cells by THP-1 monocytes. J Immunol. 2006 Feb 15;176(4):2600-9. doi: 10.4049/jimmunol.176.4.2600.

    PubMed 16456022

  • Kennedy AD, Beum PV, Solga MD, DiLillo DJ, Lindorfer MA, Hess CE, Densmore JJ, Williams ME, Taylor RP. Rituximab infusion promotes rapid complement depletion and acute CD20 loss in chronic lymphocytic leukemia. J Immunol. 2004 Mar 1;172(5):3280-8. doi: 10.4049/jimmunol.172.5.3280.

    PubMed 14978136

  • Aue G, Lindorfer MA, Beum PV, Pawluczkowycz AW, Vire B, Hughes T, Taylor RP, Wiestner A. Fractionated subcutaneous rituximab is well-tolerated and preserves CD20 expression on tumor cells in patients with chronic lymphocytic leukemia. Haematologica. 2010 Feb;95(2):329-32. doi: 10.3324/haematol.2009.012484. Epub 2009 Aug 13.

    PubMed 19679883

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Rituximab in people with Refractory Chronic Lymphocytic Leukemia, run by National Heart, Lung, and Blood Institute (NHLBI) 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 6 inclusion and 13 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: finished, as of the sponsor's last update on 2 Jul 2017. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Safety profile and early evidence of efficacy of Rituxan given subcutaneously. (time frame: 12 weeks). 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 NCT00366418, which also lists 4 linked publications.

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 2 Jul 2017.

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