A Study Using Two Oral Chemotherapy Agents for Chronic Lymphocytic Leukemia

NCT00829647 | Withdrawn Phase 1

• 1 other identifier: SCLL084993
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Dasatinib and lenalidomide are both prescribed for use in patients with different cancers of the blood. This study is experimental because neither drug has been approved by the Food and Drug Administration for the treatment of chronic lymphocytic leukemia. There are few standard treatments when fludarabine is no longer effective in patients with CLL. Some patients have received additional combination therapy with fludarabine, Campath, bone marrow transplants or supportive care. Dasatinib and lenalidomide have been effective in high-risk CLL patients in other pilot mono therapy studies. The combination of dasatinib and lenalidomide has not been studied in humans before and this study is designed to test whether this combination is safe to use.

Conditions

Chronic Lymphocytic Leukemia; Leukemia

Keywords

CLL; dasatinib; lenalidomide; sprycel; revlimid; CLL relapsed or refractory to fludarabine

Outcome Measures

Primary Outcomes (1)

• Safety and maximum tolerated dose (phase I) and overall response rate (phase II)

  6 months

Secondary Outcomes (1)

• Assess responses in subgroups of high-risk patients, including 17p- and 11q- deletion, and CD38 and ZAP-70 positive expression

  16 months

Study Arms (1)

combination dasatinib plus lenalidomide

EXPERIMENTAL

dasatinib 70 mg po daily plus lenalidomide 2.5 md po daily

Drug: dasatinib and lenalidomide

Interventions

dasatinib and lenalidomide DRUG

dasatinib will be started at 70mg/day po and lenalidomide will be started at 2.5mg/day po

Also known as: spyrcel and revlimid

combination dasatinib plus lenalidomide

Eligibility Criteria

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

You may qualify if:

• Understand and voluntarily sign a written informed consent including a HIPAA form according to institutional guidelines
• Age ≥18 years at the time of signing the informed consent form.
• Able to adhere to the study visit schedule and other protocol requirements.
• Immunophenotypically confirmed diagnosis of B-CLL, who either have Rai stage III/IV disease or require treatment for Rai stage I/II disease as defined by criteria based on the NCI 1996 guidelines (Appendix VII and IX).
• Relapsed and/or refractory disease to a purine nucleoside analogue (pentostatin, fludarabine, or cladribine). Relapse is defined as a patient who has previously achieved the clinicopathologic criteria for a CR or PR, but after a period of ≥ 6 months demonstrates evidence of disease progression. Refractory is defined as a patient progressing on therapy or who cannot maintain at least a PR for ≥ 6 months (Appendix IV). The patient may have had therapy subsequent to receiving a purine nucleoside analogue, but must also have relapsed or been refractory to this most recent therapy (Appendix IV).
• ECOG performance status of ≤ 2 at study entry (see Appendix X).
• Laboratory test results within these ranges:
• Absolute neutrophil count ≥ 1,000/mm3
• Platelet count ≥ 50,000/mm³
• Serum creatinine ≤ 1.5 mg/dL. Subjects with serum creatinine \> 1.5 mg/dL may be eligible if they have creatinine clearance of ≥ 60 mL/min by Cockroft-Gault formula.
• Total bilirubin ≤ 1.5 mg/dL
• AST (SGOT) and ALT (SGPT) ≤ 2 x ULN or ≤ 5 x ULN if hepatic metastases are present.
• Disease free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast. Patients with low- and intermediate-risk prostate cancer who have had either local therapy (radiation or surgery) or are actively receiving hormonal therapy will also be allowed. Patients being observed with "watchful waiting" will be excluded. Low- and intermediate-risk prostate cancer will be defined as PSA ≤ 20, Gleason score ≤ 7, and AJCC clinical stage of ≤ T2b.
• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and 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. 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 patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. See Appendix I: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods, AND also Appendix II: Education and Counseling Guidance Document.
• Ability to take oral medication (dasatinib and lenalidomide must be swallowed whole).

You may not qualify if:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide and/or dasatinib)
• 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.
• Use of any other experimental drug or therapy within 28 days of baseline.
• Known hypersensitivity to thalidomide
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Any prior use of lenalidomide or dasatinib
• Known positive for HIV or infectious hepatitis, type A, B or C.
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
• Women who:
• are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug, or
• have a positive pregnancy test at baseline, or
• are pregnant or breastfeeding
• Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib)
• quinidine, procainamide, disopyramide

Sponsors & Collaborators

• Scripps Health: lead
• Bristol-Myers Squibb: collaborator
• Celgene Corporation: collaborator

Related Publications (2)

• Chanan-Khan A, Miller KC, Musial L, Lawrence D, Padmanabhan S, Takeshita K, Porter CW, Goodrich DW, Bernstein ZP, Wallace P, Spaner D, Mohr A, Byrne C, Hernandez-Ilizaliturri F, Chrystal C, Starostik P, Czuczman MS. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. J Clin Oncol. 2006 Dec 1;24(34):5343-9. doi: 10.1200/JCO.2005.05.0401. Epub 2006 Nov 6.

  PMID: 17088571 BACKGROUND

• Ferrajoli A, Lee BN, Schlette EJ, O'Brien SM, Gao H, Wen S, Wierda WG, Estrov Z, Faderl S, Cohen EN, Li C, Reuben JM, Keating MJ. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood. 2008 Jun 1;111(11):5291-7. doi: 10.1182/blood-2007-12-130120. Epub 2008 Mar 11.

  PMID: 18334676 BACKGROUND

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia

Interventions

Dasatinib; Lenalidomide

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; 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)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Darren Sigal, MD

  Staff Scripps Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 23, 2009
• First Posted: January 27, 2009
• Study Start: January 1, 2009
• Primary Completion: December 1, 2009
• Study Completion: March 1, 2016
• Last Updated: April 11, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share