Alternating Thalidomide and Lenalidomide Therapy Plus Rituximab (THRiL) as Initial Treatment for Patients With CLL

This study is currently recruiting participants.
Verified June 2013 by Weill Medical College of Cornell University
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT01125176
First received: April 23, 2010
Last updated: June 17, 2013
Last verified: June 2013
  Purpose

Our hypothesis is that treatment of CLL with an alternating daily dosing schedule of thalidomide and lenalidomide may result in better tolerability by decreasing each agent's individual toxicities, while preserving efficacy, and therefore lead to a longer duration of therapy and improved responses. Additionally, the combination of the 2 agents may have additive or synergistic effects therapeutically.

In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. Starting with cycle 1, patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.)


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: thalidomide
Drug: lenalidomide
Biological: rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Daily Alternating Thalidomide and Lenalidomide Therapy Plus Rituximab (THRiL) as Initial Treatment for Patients With CLL

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • number of patients who experience a response (complete or partial) to treatment [ Time Frame: estimation of 24 months to determine response rate for all subjects ] [ Designated as safety issue: No ]
    Response and progression will be evaluated in this study using the International Workshop on CLL (IWCLL) update of the 1996 NCI-Working Group criteria for CLL


Estimated Enrollment: 24
Study Start Date: May 2012
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All subjects
In Cycle -1, even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Starting with cycle 1, all patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.)
Drug: thalidomide
50 mg oral dosing every other day
Other Name: Thalomid
Drug: lenalidomide
varying oral doses every other day (max 25 mg/day)
Other Name: Revlimid
Biological: rituximab
375 mg/m2 intravenously on days 1, 8, 15, and 22 of cycle 1. Then, repeated on days 1, 8, 15, and 22 of every 6th cycle thereafter (Cycle 7, 13, 19, etc.)
Other Name: Rituxan

Detailed Description:

This is an open label, phase II, single arm, and single institution study investigating daily alternating therapy with IMiD™ compounds, thalidomide and lenalidomide, plus rituximab in untreated CLL patients requiring treatment. In order to obtain correlative samples, patients will receive a two week course of single agent thalidomide or lenalidomide before beginning treatment with the combination regimen. Half of the patients (odd numbered subjects) will start with a two week course of single agent thalidomide and the other half of the patients (even numbered subjects) will start with a two week course of single agent lenalidomide. This will allow the study of correlative samples of monotherapy with either IMiD™ agent. In Cycle -1 half of the patients (odd numbered subjects) will receive thalidomide 50mg PO daily on days 1-14, followed by no treatment days 15-28 and the other half of the patients (even numbered subjects) will receive lenalidomide PO daily on days 1-14, followed by no treatment days 15-28. Starting cycle 1: Patients will receive thalidomide 50 mg every other day (every odd day on days 1-28: Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 & 27 of a 28 day cycle) alternating with lenalidomide on alternate every other day, dosed based upon current level with stepwise incremental dosing (every even day on days 1-28: Days 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 & 28 of a 28 day cycle). The starting dose of lenalidomide will be based on calculated creatinine clearance and the dose of lenalidomide may be escalated as tolerated to maximal dose of 25 mg (see Section 5 for details). 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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed diagnosis of CLL or SLL:
  2. No prior therapy for CLL, including treatment for autoimmune conditions that have developed since the initial diagnosis of CLL.
  3. Active disease requiring therapy:

    1. Evidence of progressive marrow failure as manifested by the development of worsening of anemia and / or thrombocytopenia
    2. Massive, progressive, or symptomatic splenomegaly
    3. Massive, progressive, or symptomatic lymphadenopathy
    4. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or a lymphocyte doubling time of less than 6 months.
    5. Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids or other standard therapy
    6. Presence of disease related symptoms: unintentional weight loss of more than 10% within previous 6 months, significant fatigue, fevers greater than 100.5 F or 38.0 C for 2 or more weeks without evidence of infection, night sweats > 1 month without evidence of infection.
  4. Understand and voluntarily sign an informed consent form.
  5. Age > = 18 years at the time of signing the informed consent form.
  6. Able to adhere to the study visit schedule and other protocol requirements.
  7. ECOG performance status of < = 2 at study entry
  8. Labs within these ranges:

    • ANC > = 1000/mm³
    • Platelets > = 50,000/mm³
    • Creatinine clearance of ≥ 30 mL/min by Cockcroft-Gault formula.
    • Total bilirubin < = 1.5 x the ULN
    • AST (SGOT) and ALT (SGPT) < = 3 x ULN (or < = 5 x ULN if due to the CLL)
  9. 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.
  10. All study participants must be registered into the mandatory S.T.E.P.S.® program, and be willing and able to comply with the requirements of S.T.E.P.S.®
  11. Females of childbearing potential (FCBP)† must have a negative pregnancy test 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.
  12. Able to take aspirin 81 or 325 mg daily as prophylactic anticoagulation, unless already on therapeutic anticoagulation.

Exclusion Criteria:

  1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from providing informed consent.
  2. 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.
  3. Evidence of laboratory TLS by Cairo-Bishop Definition of Tumor Lysis Syndrome. Subjects may be enrolled upon correction of electrolyte abnormalities.
  4. Concurrent use of other anti-cancer agents or treatments.
  5. Prior treatment with thalidomide or lenalidomide.
  6. Active serious infection not controlled with antibiotics.
  7. Autoimmune hemolytic anemia or thrombocytopenia requiring treatment.
  8. Known positive for HIV
  9. Active infection with hepatitis B, defined by being positive for HepBsAg or Hep B DNA by PCR, or hepatitis C
  10. Pre-existing peripheral neuropathy > = grade 2
  11. Pregnant or breast feeding females.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01125176

Contacts
Contact: Richard Furman, MD 212-746-2063 rrfurman@med.cornell.edu
Contact: Bridgid Thomas, RN 212-746-1362

Locations
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
Contact: Richard Furman, MD    646-962-2064    rrfurman@med.cornell.edu   
Contact: Amelyn Rodriguez, RN    212-746-1362      
Principal Investigator: Richard Furman, MD         
Sponsors and Collaborators
Weill Medical College of Cornell University
Celgene Corporation
Investigators
Principal Investigator: Richard Furman, MD Weill Medical College of Cornell University
  More Information

Additional Information:
No publications provided

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT01125176     History of Changes
Other Study ID Numbers: 1002010897, RV-CLL-PI-0391
Study First Received: April 23, 2010
Last Updated: June 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:
CLL

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Thalidomide
Rituximab
Lenalidomide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 15, 2014