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Waldenstrom MacroglobulinemiaPhase 2THRiL for WMNCT01779167

Thalidomide, Lenalidomide, and Rituximab for Previously Treated Waldenstrom Macroglobulinemia

A Phase 2 study testing Thalidomide, Lenalidomide and Rituximab in people with Waldenstrom Macroglobulinemia, run by Weill Medical College of Cornell University 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

The purpose of this study is to evaluate the efficacy and safety of daily alternating thalidomide and lenalidomide plus rituximab (ThRiL) in patients with previously treated Waldenstrom macroglobulunemia (WM). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Waldenstrom Macroglobulinemia
What is being tested?
Thalidomide, Lenalidomide and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
Jun 2012to Apr 2014
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

  • Histologically confirmed diagnosis of WM
  • At least one prior systemic therapy
  • Measurable disease, defined as quantifiable monoclonal IgM > 1000 mg/dL
  • Active disease requiring therapy defined as at least one of the following five criteria:
  • Rising IgM
  • Hemoglobin < 20 g/dL
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  • Platelet count < 100 x 109/L
  • Symptomatic or bulky lymphadenopathy or organomegaly
  • Systemic manifestations of WM, including hyperviscosity, neuropathy, amyloidosis, cryoglobulinemia, B symptoms.
  • note: subjects with symptomatic hyperviscosity or a serum viscosity of > 3.5 CP are eligible but should undergo plasmapheresis prior to initiation of treatment
  • Understand and voluntarily sign an informed consent form
  • Age >18 years at the time of signing the informed consent form
  • Able to adhere to the study visit schedule and other protocol requirements
  • ECOG performance status ≤ at study entry
  • Laboratory test results within these ranges:
  • Absolute neutrophil count ≥ 1000/mm³
  • Platelet count ≥ 50,000/mm³
  • Creatinine clearance of ≥ 30 mL/min by Cockroft-Gault formula.
  • Total bilirubin ≤ 1.5 times the ULN, unless abnormality is the result of Gilbert's disease or the result of the WM
  • AST (SGOT) and ALT (SGPT) ≤ 3 x ULN
  • Disease free of prior malignancies for ≥ 2 years with exception of curatively treated basal cell carcinoma, 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 ® (RASP: RevAssist ® for Study Participants) and S.T.E.P.S. ® (P-TAP: Protocol Therapy Assistant Program) programs and be willing and able to comply with the requirements of RevAssist ® and S.T.E.P.S. ®.
  • Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting treatment and again within 24 hours before the first dose of lenalidomide AND thalidomide. FCBP 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 and/or thalidomide. 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. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. See Appendix A: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.
  • Able to take aspirin 81 or 325 mg daily or low molecular weight heparin as prophylactic anticoagulation, unless already on therapeutic anticoagulation. Subjects intolerant to ASA may use warfarin or low molecular weight heparin.

Who cannot join

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from providing informed consent.
  • 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.
  • Concurrent use of other anti-cancer agents or treatments
  • Prior treatment with thalidomide or lenalidomide
  • Active serious infection not controlled with antibiotics
  • Autoimmune hemolytic anemia or thrombocytopenia requiring treatment
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  • Known positive for HIV
  • Active infection with hepatitis B, defined by being positive for HepBsAg or Hep B DNA by PCR, or hepatitis C
  • Pre-existing peripheral neuropathy > grade 2
  • Pregnant or breast-feeding females. (Lactating females must agree not to breast feed while taking lenalidomide and/or thalidomide).
  • Disease transformation to an aggressive histology
  • Treatment for WM within the past 28 days
  • Hypersensitivity to rituximab

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Weill Cornell Medical College

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase 2 Trial of Daily Alternating Thalidomide and Lenalidomide Plus Rituximab (ThRiL) for Patients With Previously Treated Waldenstrom Macroglobulinemia

The purpose of this study is to evaluate the efficacy and safety of daily alternating thalidomide and lenalidomide plus rituximab (ThRiL) in patients with previously treated Waldenstrom macroglobulunemia (WM). Thalidomide and lenalidomide are drugs that modulate the immune system and have been shown to bring about responses in subjects with WM. However, their use has been limited due to side effects. The investigators hypothesize that alternating doses of thalidomide and lenalidomide may alleviate the side effects while preserving the effectiveness of the therapies.

Read the detailed description

Waldenstrom macroglobulinemia (WM) is an incurable B-cell lymphoproliferative disorder characterized by expansion of malignant B-lymphocytes and excessive production of monoclonal IgM. The survival and proliferation of the neoplastic WM cells is highly dependent on signals from the microenvironment. Thalidomide and lenalidomide are immunomodulatory agents with single agent activity in WM. Their use is limited by significant toxicities, including tumor flare (thalidomide and lenalidomide); sedation, constipation, and neuropathy (thalidomide); and cytopenias (lenalidomide). Alternating doses of thalidomide and lenalidomide may alleviate the toxicities, while preserving efficacy since the agents have non-overlapping toxicities and yet similar hypothesized mechanisms of action. Additionally, starting at a lower dose of lenalidomide than previously studied in WM may allow for improved tolerability. A pilot study of daily alternating therapy in subjects with chronic lymphocytic leukemia demonstrated that the two agents could be combined with non-overlapping toxicity. This phase II study aims to evaluate the efficacy and safety of daily alternating thalidomide and lenalidomide plus rituximab (ThRiL) in subjects with previously treated WM.

Subjects will receive thalidomide 50 mg every other day (i.e., every odd day: days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 \& 27 of a 28 day cycle) alternating with lenalidomide on every other day (i.e., every even day: days 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 \& 28 of a 28 day cycle), dosed based upon stepwise incremental dosing. Rituximab 375 mg/m2 will be administered on days 1, 8, 15 and 22 starting with Cycle 1 and then again on the same weekly x 4 schedule every 6th cycle thereafter (Cycles 7, 13, 19, etc).

Keywords
WM
Medical subject headings
Waldenstrom Macroglobulinemia

What participants receive

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

  • ThalidomideDrug

    Thalidomide 50 mg (every ODD day of a 28 day cycle: Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 \& 27)

  • LenalidomideDrug

    Also called Revlimid

    Lenalidomide (every EVEN day of a 28 day cycle: Days 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 \& 28). Lenalidomide will be initiated at a starting dose of 5 mg.

  • RituximabDrug

    Also called Rituxan

    Rituximab 375 mg/m2 IV on Days 1, 8, 15 and 22 (+/- 2 days) and then again on the same weekly x 4 schedule every 6th cycle thereafter (Cycle 7, 13, 19, etc).

Study groups in NCT01779167
Study groupRoleWhat they receive
All PatientsExperimentalDaily alternating thalidomide and lenalidomide plus rituximab (ThRiL) in patients with previously treated WM
Receives: Drug: Thalidomide; Drug: Lenalidomide; Drug: Rituximab

What is being measured

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

  1. Number of Patients Who Demonstrate a Response (Complete, Partial, Minor) to Treatment

    Response criteria for subjects with WM is based upon the Consensus Panel Recommendations from the Third International Workshop on Waldenstrom Macroglobulinemia.

    Overall response rate (CR + PR + MR) measured at time of best response.

    Measured: Approximately 24 months

Secondary outcomes (5)

  1. Number of Adverse Events Experienced With Alternating Thalidomide and Lenalidomide Plus Rituximab for Subjects With Previously Treated Waldenstrom's Macroglobulinemia

    Capture the number of adverse events experienced when combining thalidomide, lenalidomide, and rituximab in patients with previously treated WM

    Measured: approximately 24 months per patient

  2. Survival of Subjects Treated With THRiL for WM.

    Estimate overall survival of patients enrolled on THRiL for WM.

    Measured: approximately 24 months per patient

  3. Rate of Rituximab Related IgM Flare

    Estimate the rate of rituximab-related IgM flare

    Measured: Approximately 24 months per patient

  4. Time to Response

    Measure the time from initiating therapy to demonstrating response in WM.

    Measured: approximately 24 months

  5. Response Duration of Subjects Treated With THRiL for WM

    Measure response duration of patients enrolled on THRiL for WM

    Measured: 24 months

Timeline

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

  1. First posted30 Jan 2013 (estimated)
  2. Study startJun 2012
  3. Primary completionOct 2013
  4. Study completionApr 2014

Why it stopped: Slow Accrual

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
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01779167
Sponsor's protocol ID
1112012086
Other IDs
RV-WM-PI-0690
Acronym
THRiL for WM
Status last verified
Jun 2018
First submitted
7 Jan 2013
Last updated
11 Jul 2018
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Thalidomide, Lenalidomide and Rituximab in people with Waldenstrom Macroglobulinemia, run by Weill Medical College of Cornell University 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 24 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: stopped early, as of the sponsor's last update on 11 Jul 2018. 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 Apr 2017). 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?

Number of Patients Who Demonstrate a Response (Complete, Partial, Minor) to Treatment (time frame: Approximately 24 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 NCT01779167.

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 11 Jul 2018.

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