Thalidomide in Treating Patients With Relapsed Chronic Lymphocytic Leukemia

A Phase II Trial of Thalidomide in Patients With Relapsed Chronic Lymphocytic Leukemia

Phase II trial to study the effectiveness of thalidomide in treating patients who have relapsed chronic lymphocytic leukemia. Thalidomide may stop the growth of chronic lymphocytic leukemia by stopping blood flow to the tumor.

Study Overview

• Status: Completed
• Conditions: B-cell Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: thalidomide

Detailed Description

PRIMARY OBJECTIVES:

I. To determine whether thalidomide can induce objective responses in relapsed B-CLL patients.

II. To determine the toxicity of thalidomide in this patient population. III. To document if alterations in vascular growth factors and/or bone marrow angiogenesis patterns correlate with thalidomide related clinical responses.

OUTLINE:

Patients receive oral thalidomide daily for 4 weeks. Courses repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 5 years.

• Study Type: Interventional
• Enrollment (Anticipated): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • North Central Cancer Treatment Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of chronic lymphocytic leukemia (CLL) evidenced by monoclonal population of mature CD5+, CD19+, CD23+, and B cells
• Relapsed after prior treatment for CLL

• Active disease with 1 or more of the following characteristics:

  • At least 10% weight loss within the past 6 months
  • Fever greater than 100.5 degrees F for at least 2 weeks without evidence of infection
  • Night sweats without evidence of infection
  • Evidence of progressive marrow failure with anemia (hemoglobin less than 11 g/dL) and/or thrombocytopenia (platelet count less than 100,000/mm^3) (i.e., any stage III or IV disease)
  • Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroid therapy
  • Massive or progressive splenomegaly (i.e., greater than 6 cm below the left costal margin or more than 50% increase over 2 months)
  • Progressive lymphadenopathy (i.e., more than 50% increase over 2 months)
  • Progressive lymphocytosis (not due to corticosteroids) with an increase of more than 50% over a 2-month period or an anticipated doubling time of less than 6 months
  • Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease are not considered evidence of active disease

• Measurable disease

  • Absolute lymphocyte count greater than 5,000/mm^3
• No bulky lymph node disease greater than 10 cm in at least 1 dimension except splenomegaly
• Performance status - ECOG 0-2
• Absolute neutrophil count at least 500/mm^3
• Platelet count at least 20,000/mm^3 (in absence of sargramostim [GM-CSF])
• Hemoglobin at least 8 g/dL
• Bilirubin no greater than 2.5 times upper limit of normal (ULN)
• AST no greater than 2.5 times ULN
• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 60 mL/min
• No other active malignancy
• No peripheral neuropathy (sensory) grade 2 or greater
• No active infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 1 highly effective method of contraception AND 1 additional effective method of contraception for at least 4 weeks before, during, and for 4 weeks after study completion
• No prior allogeneic bone marrow transplantation
• At least 10 days since prior filgrastim (G-CSF) or GM-CSF
• No more than 3 prior chemotherapy regimens
• At least 30 days since prior chemotherapy
• No concurrent corticosteroids except for adrenal insufficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (thalidomide); Patients receive oral thalidomide daily for 4 weeks. Courses repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Drug: thalidomide; Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed response, noted as the objective status of CR, nPR, or PR on 2 consecutive evaluations at least 4 weeks apart	Ninety percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The Kaplan-Meier method will be used.	Up to 5 years
Progression-free survival	The Kaplan-Meier method will be used.	Up to 5 years
Time to progression	The Kaplan-Meier method will be used.	Up to 5 years
Duration of response		Up to 5 years
Maximum grade of each type of toxicity	Frequency tables will be reviewed.	Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Neil Kay, North Central Cancer Treatment Group

Study record dates

Study Major Dates

• Study Start: September 1, 2000
• Primary Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: September 11, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): October 8, 2013
• Last Update Submitted That Met QC Criteria: October 7, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Thalidomide
• Other Study ID Numbers: NCI-2012-01852 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA025224 (U.S. NIH Grant/Contract); NCCTG-N9986; CDR0000068148; N9986 (Other Identifier: CTEP)