Thalidomide, Lenalidomide, and Rituximab for Previously Treated Waldenstrom Macroglobulinemia

NCT01779167 | Terminated Phase 2 Results DMC

• 2 other identifiers: 1112012086RV-WM-PI-0690
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Waldenstrom Macroglobulinemia

Keywords

WM

Outcome Measures

Primary Outcomes (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.

  Approximately 24 months

Secondary Outcomes (5)

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

  approximately 24 months per patient

• Survival of Subjects Treated With THRiL for WM.

  approximately 24 months per patient

• Rate of Rituximab Related IgM Flare

  Approximately 24 months per patient

• Time to Response

  approximately 24 months

• Response Duration of Subjects Treated With THRiL for WM

  24 months

Study Arms (1)

All Patients

EXPERIMENTAL

Daily alternating thalidomide and lenalidomide plus rituximab (ThRiL) in patients with previously treated WM

Drug: Thalidomide; Drug: Lenalidomide; Drug: Rituximab

Interventions

Thalidomide DRUG

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)

All Patients

Lenalidomide DRUG

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.

Also known as: Revlimid

All Patients

Rituximab DRUG

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).

Also known as: Rituxan

All Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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:

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Celgene Corporation: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

Thalidomide; Lenalidomide; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Peter Martin, MD
• Organization: Weill Cornell Medicine

amr2017@med.cornell.edu

646.962.2064

Study Officials

• Peter Martin, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: January 7, 2013
• First Posted: January 30, 2013
• Study Start: June 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: April 1, 2014
• Last Updated: July 11, 2018
• Results First Posted: April 7, 2017

Record last verified: 2018-06

Locations

US (1)