AzTrials
AzTrials

Follicular LymphomaPhase 2NCT00783367

Combination Therapy Using Lenalidomide (Revlimid)- Low Dose Dexamethasone and Rituximab for Treatment of Rituximab-Resistant, Non-Aggressive B-Cell Lymphomas

A Phase 2 study testing Lenalidomide, Dexamethasone and Rituximab in people with Follicular Lymphoma and Marginal Zone B-Cell Lymphoma, run by Abramson Cancer Center at Penn Medicine 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
Search all trials

Trial summary

Pre-clinical data and recently published clinical data suggest a synergistic effect between lenalidomide and dexamethasone. We hypothesize that a combination of lenalidomide-dexamethasone can overcome rituximab resistance. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Lenalidomide, Dexamethasone and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
Jul 2008to 23 Nov 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Previously treated, histologically confirmed follicular lymphoma (grade 1, 2, 3a), marginal zone lymphoma, small lymphocytic lymphoma with less than <5000 lymphocytes/mm3 or lymphoplasmacytic lymphoma with <3g/mL IgM, mantle cell lymphoma by WHO classification
  • Flow cytometry or immunohistochemistry must document CD20 antigen expression. Past documentation of CD20 antigen expression is admissible.
  • Subjects must have been treated with rituximab in combination with chemotherapy or as monotherapy and must have refractory or progressive disease <6 months from the first rituximab dose of previous rituximab containing regimen
  • At least 18 years of age
  • ECOG performance status 0-2
  • Measurable disease must be present on physical examination or imaging studies. Any tumor mass >2cm is considered measurable.
Show all 14Show fewer
  • Lesions that are considered non-measurable, but assessable include the following: bone lesions, ascites, pleural/pericardial effusion, lymphangitis cutis/pulmonis, bone marrow
  • Patients with a history of intravenous drug abuse or any behavior associated with increased risk of HIV infection should be tested for exposure to the HIV virus
  • Understand and voluntarily sign an informed consent
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant of ASA may use warfarin or low molecular weight heparin)
  • Laboratory test results within these ranges: absolute neutrophil count greater than or equal to 1500/mm3; platelet count greater than or equal to 75,000/mm3; serum creatinine less than or equal to 2.0mg/dL; total bilirubin less than or equal to 1.5mg/dL (unless due to Gilbert's syndrome); AST (SGOT) and ALT (SGPT) less than or equal to 2.5 x ULN or less than or equal to 5 x ULN if hepatic metastases are present
  • Disease free of prior malignancies for greater than or equal to 5 years with the exception of currently treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
  • All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.

Who cannot join

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from following study procedure
  • Pregnant or breast-feeding females
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Use of any other experimental drug or therapy within 28 days of baseline
  • Known hypersensitivity to thalidomide
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
Show all 9Show fewer
  • Any prior use of lenalidomide
  • Known positivity for HIV or active infectious Hepatitis, type A, B, or C. Patients who test positive or who are known to be infected are not eligible due to an increased risk of infection with this regimen. HIV testing is not required for study entry, but is required if the patient is perceived to be at risk.
  • Known central nervous system involvement by lymphoma

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Pennsylvania; Abramson Cancer Center; Lymphoma Program

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: Phase 2 Trial of Lenalidomide (Revlimid)-Dexamethasone + Rituximab in Recurrent Small B-Cell Non-Hodgkin Lymphomas (NHL) Resistant to Rituximab

Pre-clinical data and recently published clinical data suggest a synergistic effect between lenalidomide and dexamethasone. We hypothesize that a combination of lenalidomide-dexamethasone can overcome rituximab resistance. To determine the response rate to lenalidomide and dexamethasone plus rituximab therapy in subjects with recurrent small B-cell non-Hodgkin lymphoma who have had lymphoma progression within 6 months of being treated with rituximab alone or with a rituximab-containing regimen, we propose initial treatment with both drugs for two 28-day treatment cycles (Part I). After response assessment following two cycles of lenalidomide-dexamethasone, patients will enter Part II of the study. In Part II, patients will receive lenalidomide-dexamethasone and rituximab to evaluate the potential reversal of rituximab resistance as measured by response to rituximab and progression-free survival following rituximab.

Keywords
Revlimid, Celgene brand of lenalidomide, lenalidomide, Rituxan, CD20 antibody, rituximab, rituximab, Follicular Lymphoma, Marginal Zone B-Cell Lymphoma, Lymphoma, Small Lymphocytic, Waldenstrom Macroglobulinemia, Mantle-Cell Lymphoma, Antigens, CD20, refractory, resistantRefractory/progressive lymphoma less than 6 months from first rituximab dose of previous rituximab-containing regimen, Previously treated, Treated with rituximab
Medical subject headings
Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Leukemia, Lymphocytic, Chronic, B-Cell, Waldenstrom Macroglobulinemia, Lymphoma, Mantle-Cell

What participants receive

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

  • LenalidomideDrug

    Also called Revlimid (lenalidomide)

    Lenalidomide: 10mg capsules, orally, once daily for each 28 day cycle for the duration of the study

  • DexamethasoneDrug

    Also called Decadron (dexamethasone)

    Dexamethasone: 8mg tablets, orally, once weekly on days 3, 10, 17, 24 of each 28 day cycle for the duration of the study;

  • RituximabDrug

    Also called Rituxan (rituximab)

    Rituximab: 375mg/m2 IV (in the vein), once weekly on days 1, 8, 15, 22 during month 3 of therapy

Study groups in NCT00783367
Study groupRoleWhat they receive
Lenalidomide plus rituximab with dexamethasoneExperimentalLenalidomide-low dose dexamethasone plus rituximab
Receives: Drug: Lenalidomide; Drug: Dexamethasone; Drug: Rituximab

What is being measured

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

  1. Response Rate to Lenalidomide-dexamethasone + Rituximab Therapy in Relapsed Small B-cell Lymphoma With Rituximab Resistance

    Response rate is defined as a complete response or partial response using anatomic criteria of the International Workshop Response Critieria (Cheson, 1999).

    Measured: 3 months

Secondary outcomes (1)

  1. Time Until Progression After Lenalidomide-dexamethasone + Rituximab Therapy in Relapsed Small B-cell Lymphomas With Rituximab Resistance

    Progression free survival time in months

    Measured: 9 years from enrollment of first subject

Timeline

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

  1. First posted31 Oct 2008 (estimated)
  2. Study startJul 2008
  3. Primary completion14 Nov 2012
  4. Study completion23 Nov 2020

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
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00783367
Sponsor's protocol ID
UPCC 02408
Other IDs
UPenn IRB#807684, RV-NHL-PI-0296
Status last verified
Mar 2023
First submitted
30 Oct 2008
Last updated
30 Mar 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998 Aug;16(8):2825-33. doi: 10.1200/JCO.1998.16.8.2825.

    PubMed 9704735

  • Davis TA, Grillo-Lopez AJ, White CA, McLaughlin P, Czuczman MS, Link BK, Maloney DG, Weaver RL, Rosenberg J, Levy R. Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin's lymphoma: safety and efficacy of re-treatment. J Clin Oncol. 2000 Sep;18(17):3135-43. doi: 10.1200/JCO.2000.18.17.3135.

    PubMed 10963642

  • Golay J, Lazzari M, Facchinetti V, Bernasconi S, Borleri G, Barbui T, Rambaldi A, Introna M. CD20 levels determine the in vitro susceptibility to rituximab and complement of B-cell chronic lymphocytic leukemia: further regulation by CD55 and CD59. Blood. 2001 Dec 1;98(12):3383-9. doi: 10.1182/blood.v98.12.3383.

    PubMed 11719378

  • Golay J, Zaffaroni L, Vaccari T, Lazzari M, Borleri GM, Bernasconi S, Tedesco F, Rambaldi A, Introna M. Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood. 2000 Jun 15;95(12):3900-8.

    PubMed 10845926

  • Harjunpaa A, Junnikkala S, Meri S. Rituximab (anti-CD20) therapy of B-cell lymphomas: direct complement killing is superior to cellular effector mechanisms. Scand J Immunol. 2000 Jun;51(6):634-41. doi: 10.1046/j.1365-3083.2000.00745.x.

    PubMed 10849376

  • Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene. 2003 Oct 20;22(47):7359-68. doi: 10.1038/sj.onc.1206939.

    PubMed 14576843

  • Hofmeister JK, Cooney D, Coggeshall KM. Clustered CD20 induced apoptosis: src-family kinase, the proximal regulator of tyrosine phosphorylation, calcium influx, and caspase 3-dependent apoptosis. Blood Cells Mol Dis. 2000 Apr;26(2):133-43. doi: 10.1006/bcmd.2000.0287.

    PubMed 10753604

  • Clynes RA, Towers TL, Presta LG, Ravetch JV. Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med. 2000 Apr;6(4):443-6. doi: 10.1038/74704.

    PubMed 10742152

  • Cartron G, Dacheux L, Salles G, Solal-Celigny P, Bardos P, Colombat P, Watier H. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood. 2002 Feb 1;99(3):754-8. doi: 10.1182/blood.v99.3.754.

    PubMed 11806974

  • Weng WK, Levy R. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol. 2003 Nov 1;21(21):3940-7. doi: 10.1200/JCO.2003.05.013. Epub 2003 Sep 15.

    PubMed 12975461

  • Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, Newman RA, Hanna N, Anderson DR. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994 Jan 15;83(2):435-45.

    PubMed 7506951

  • van der Kolk LE, Grillo-Lopez AJ, Baars JW, Hack CE, van Oers MH. Complement activation plays a key role in the side-effects of rituximab treatment. Br J Haematol. 2001 Dec;115(4):807-11. doi: 10.1046/j.1365-2141.2001.03166.x.

    PubMed 11843813

  • Alas S, Emmanouilides C, Bonavida B. Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin's lymphoma to apoptosis. Clin Cancer Res. 2001 Mar;7(3):709-23.

    PubMed 11297268

  • Bohen SP, Troyanskaya OG, Alter O, Warnke R, Botstein D, Brown PO, Levy R. Variation in gene expression patterns in follicular lymphoma and the response to rituximab. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1926-30. doi: 10.1073/pnas.0437875100. Epub 2003 Feb 5.

    PubMed 12571354

  • Dave SS, Wright G, Tan B, Rosenwald A, Gascoyne RD, Chan WC, Fisher RI, Braziel RM, Rimsza LM, Grogan TM, Miller TP, LeBlanc M, Greiner TC, Weisenburger DD, Lynch JC, Vose J, Armitage JO, Smeland EB, Kvaloy S, Holte H, Delabie J, Connors JM, Lansdorp PM, Ouyang Q, Lister TA, Davies AJ, Norton AJ, Muller-Hermelink HK, Ott G, Campo E, Montserrat E, Wilson WH, Jaffe ES, Simon R, Yang L, Powell J, Zhao H, Goldschmidt N, Chiorazzi M, Staudt LM. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med. 2004 Nov 18;351(21):2159-69. doi: 10.1056/NEJMoa041869.

    PubMed 15548776

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lenalidomide, Dexamethasone and Rituximab in people with Follicular Lymphoma and Marginal Zone B-Cell Lymphoma, run by Abramson Cancer Center at Penn Medicine 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 9 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 30 Mar 2023. 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?

Yes. Results are posted in the registry (first posted 7 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Response Rate to Lenalidomide-dexamethasone + Rituximab Therapy in Relapsed Small B-cell Lymphoma With Rituximab Resistance (time frame: 3 months). 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 NCT00783367, which also lists 24 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 30 Mar 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in
Clinical Trial NCT00783367 | AzTrials