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

NCT01125176 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 1112012062RV-CLL-PI-0391
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators' 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.)

Conditions

Chronic Lymphocytic Leukemia

Keywords

CLL

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate as Defined as the Number of Patients Who Experience a Response (Complete or Partial) to Treatment at the Time of Best Response

  Response will be evaluated in this study using the International Workshop on CLL (IWCLL) update of the 1996 NCI-Working Group criteria for CLL, which includes assessment of the following: clonal lymphocytes in the peripheral blood by flow cytometry, blood tests for neutrophil count, hemoglobin, and platelet count, CT examination for lymphadenopathy, hepatomegaly, splenomegaly, constitutional symptoms, bone marrow assessment via biopsy/aspirate, and evaluation for disease transformation.

  From date of study drug initiation until date of best response, assessed up to 6 years.

Secondary Outcomes (4)

• Progression Free Survival

  From date of study drug initiation until date of progression or death, whichever occurs first, assessed through study completion up to 100 months.

• Duration of Response

  From date of end of treatment to progression or death, whichever occurs first, assessed through study completion up to 100 months.

• Time to Response

  From date of study drug initiation to date of initial response, assessed up to 12 months.

• Overall Survival

  From date of study drug initiation to date of death, assessed through study completion up to 105 months.

Study Arms (1)

All subjects

EXPERIMENTAL

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; Drug: lenalidomide; Biological: rituximab

Interventions

thalidomide DRUG

50 mg oral dosing every other day

Also known as: Thalomid

All subjects

lenalidomide DRUG

varying oral doses every other day (max 25 mg/day)

Also known as: Revlimid

All subjects

rituximab BIOLOGICAL

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.)

Also known as: Rituxan

All subjects

Eligibility Criteria

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

You may qualify if:

• \. Confirmed diagnosis of CLL or SLL based upon standard criteria as outlined in the IWCLL Update of the 1996 NCI-Working Group criteria for CLL:
• a) Presence of one of the following:
• \. more than or equal to 5 x 10\^9 B lymphocytes/L in the peripheral blood for a duration of at least 3 months. Patients with a B lymphocytosis will be characterized as CLL, while those without will be characterized as SLL
• \. the presence of lymphadenopathy resulting from infiltration with lymphocytes with the phenotype of CLL
• \. bone marrow infiltration with lymphocytes with the phenotype of CLL
• b) Lymphocytes with the morphologic appearance of small, mature appearing lymphocytes, with less or equal to 55 percent prolymphocytes (blood or bone marrow)
• c) Cellular phenotype characterized by the:
• co-expression of the CD5, CD20, and CD23 surface antigens
• clonal kappa or lambda light chain expression
• dim surface immunoglobulin expression
• \. No prior therapy for CLL, including treatment for autoimmune conditions that have developed since the initial diagnosis of CLL.
• \. Active disease requiring therapy as defined by the IWCLL Update of the 1996 NCIWG guidelines:
• Evidence of progressive marrow failure as manifested by the development of worsening of anemia and / or thrombocytopenia
• Massive, progressive, or symptomatic splenomegaly
• Massive, progressive, or symptomatic lymphadenopathy

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.
• Evidence of laboratory TLS by Cairo-Bishop Definition of Tumor Lysis Syndrome. Subjects may be enrolled upon correction of electrolyte abnormalities.
• 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 greater than grade 2
• Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide and/or thalidomide).

Sponsors & Collaborators

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

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Thalidomide; Lenalidomide; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: Richard Furman, MD
• Organization: Weill Cornell Medical College

rrfurman@med.cornell.edu

646-962-2064

Study Officials

• Richard Furman, 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: April 23, 2010
• First Posted: May 18, 2010
• Study Start: March 30, 2012
• Primary Completion: December 20, 2018
• Study Completion: December 29, 2020
• Last Updated: January 21, 2022
• Results First Posted: August 26, 2019

Record last verified: 2021-12

Locations

US (1)