Clinical trial NCT00398112: Sunitinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Official title: A Phase II Study of Sunitinib Malate for Treatment of Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: B-cell Chronic Lymphocytic Leukemia
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-11-10
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is studying how well sunitinib works in treating patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. Sunitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.

Detailed description: PRIMARY OBJECTIVES:

I. Assess the response rate (complete response \[CR\] and partial response) in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma treated with sunitinib malate.

II. Assess the toxicity of this drug in these patients. III. Assess duration of response, time to progression, overall survival, and CR rate in patients treated with this drug.

SECONDARY OBJECTIVES:

I. Evaluate if known risk stratification parameters (i.e., immunoglobulin mutational status, ZAP-70 status, fluorescent in situ hybridization \[FISH\] defects, and/or CD38 status) are related to clinical response to sunitinib malate.

OUTLINE: This is a multicenter study.

Patients receive oral sunitinib malate daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection periodically for translational and pharmacological studies, including IgVH gene mutation status and ZAP-70 status. Samples are examined by fluorescent in situ hybridization (FISH) and other assays.

After completion of study treatment, patients are followed every 3 months for up to 2 years.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of 1 of the following:

  * Biopsy proven small lymphocytic lymphoma (SLL)
  * Chronic lymphocytic leukemia (CLL) meeting all of the following criteria:

    * Peripheral blood lymphocyte count \> 5,000/mm\^3
    * Lymphocytes must consist of small to moderate size lymphocytes, with \< 55% prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically
    * Immunophenotyping consistent with CLL, defined by the following criteria:

      * Predominant population of lymphocytes share both B-cell antigens (i.e., CD19, CD20, or CD23) as well as CD5 in the absence of other pan-T-cell markers (e.g., CD3 or CD2)
      * Dim surface immunoglobulin expression
      * Exclusively kappa and lambda light chains
      * Splenomegaly, hepatomegaly, or lymphadenopathy are not required
* Refractory or relapsed disease as evidenced by 1 of the following criteria:

  * Progression after ≥ 1 course of a purine nucleoside (i.e., fludarabine phosphate, cladribine, pentostatin) regimen
  * Progression after ≥ 1 course of an alkylator (i.e., cyclophosphamide or chlorambucil) regimen
  * Relapse after ≥ 1 prior purine nucleoside oral kylator (i.e., cyclophosphamide or chlorambucil) regimen
* Requires chemotherapy, as indicated by any of the following criteria:

  * Measurable (i.e., \> 5,000/mm\^3) and progressive clonal lymphocytosis
  * Measurable (i.e., single diameter \> 2 cm) and progressive lymphadenopathy
  * Disease-related symptoms, including 1 or more of the following:

    * Weight loss \> 10% within the past 6 months
    * Extreme fatigue attributed to CLL/SLL
    * Fevers \> 100.5\^oF for 2 weeks without evidence of infection
    * Night sweats without evidence of infection
  * Evidence of progressive marrow failure, as manifested by the development of or worsening anemia (hemoglobin \< 10 g/dL) and/or thrombocytopenia (platelet count \< 100,000/mm\^3)
  * Massive (i.e. \> 6 cm below left costal margin) or progressives plenomegaly
* No mantle cell lymphoma, as demonstrated by a negative fluorescent in situ hybridization (FISH) analysis fort(11;14)(IgVH/CCND1) on peripheral blood or tissue biopsy
* ECOG performance status 0-2
* Life expectancy ≥ 12 months
* Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 60 mL/min
* AST and ALT ≤ 2.5 times ULN
* Bilirubin normal
* Alkaline phosphatase ≤ 3 times ULN
* Platelet count \> 30,000/mm\^3 (without transfusion)
* Absolute neutrophil count \> 1,000/mm\^3
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Able to complete patient diaries alone or with assistance
* No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
* No other malignancy except for squamous cell or basal cell carcinoma of the skin or in situ carcinoma of the cervix, unless the tumor was curatively treated within the past 2 years
* No history of allergic reactions attributed to compounds of similar chemical or biological composition to sunitinib malate
* No inability to swallow or retain sunitinib malate capsules due to any of the following:

  * Gastrointestinal tract disease
  * Requirement for IV alimentation
  * Prior surgical procedures affecting absorption
  * Active peptic ulcer disease
* No pre-existing thyroid abnormality that would make the patient unable to maintain normal thyroid function with medication
* No pulmonary embolism within the past 12 months
* No serious or nonhealing wound, ulcer, or bone fracture
* No uncontrolled intercurrent illness including, but not limited to, any of the following:

  * Ongoing or active infections
  * Psychiatric illness or social situation that would limit compliance with study requirements
* No cerebrovascular accident or transient ischemic attack within the past 12 months
* No uncontrolled hypertension (i.e., systolic blood pressure \[BP\] ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg)
* No significant cardiac arrhythmia, including any of the following:

  * QTc prolongation (i.e., QTc interval ≥ 500 msec)
  * Ventricular tachycardia
  * Atrial fibrillation
  * Atrial flutter
  * Second or third degree heart block
* No cardiac disease within the past 12 months, including any of the following:

  * Myocardial infarction
  * Cardiac arrhythmia
  * Stable/unstable angina
  * Symptomatic congestive heart failure
  * Coronary/peripheral artery bypass graft or stenting
* No New York Heart Association (NYHA) class III or IV heart failure

  * The following patients are eligible provided they have NYHA class II cardiac function on baseline ECHO/MUGA:

    * History of NYHA class II heart failure and asymptomatic on treatment
    * No prior anthracycline exposure
    * No prior central thoracic radiation that included the heart in the radiation port
* See Disease Characteristics
* At least 4 weeks since prior chemotherapy
* At least 4 weeks since prior rituximab or alemtuzumab
* At least 4 weeks since prior major surgery
* At least 4 weeks since prior oral steroids
* No prior treatment with any other antiangiogenic agent, including any of the following:

  * Bevacizumab
  * Sorafenib
  * Pazopanib
  * AZD2171
  * Vatalanib
  * VEGF Trap
* At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:

  * Ketoconazole
  * Itraconazole
  * Clarithromycin
  * Erythromycin
  * Diltiazem
  * Verapamil
  * HIV protease inhibitors (i.e., indinavir, saquinavir,ritonavir, atazanavir, nelfinavir)
  * Delavirdine
* At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:

  * Rifampin
  * Rifabutin
  * Carbamazepine
  * Phenobarbital
  * Phenytoin
  * Hypericum perforatum (St. John's wort)
  * Efavirenz
  * Tipranavir
* No other concurrent investigational agents
* No concurrent agents with proarrhythmic potential, including any of the following:

  * Terfenadine
  * Quinidine
  * Procainamide
  * Disopyramide
  * Sotalol
  * Probucol
  * Bepridil
  * Haloperidol
  * Risperidone
  * Indapamide
  * Flecainide
* No concurrent combination antiretroviral therapy for HIV-positive patients
* No other concurrent anticancer agents or therapies
* No concurrent therapeutic doses of coumarin-derivative anticoagulants (e.g., warfarin)

  * Concurrent prophylactic low molecular weight heparin or warfarin at doses ≤ 2 mg daily for thrombosis prophylaxis allowed

Primary outcomes:
measure: Number of Participants With a Confirmed Response [Complete Response (CR) and Partial Response (PR)] on 2 Consecutive Evaluations at Least 4 Weeks Apart
timeFrame: Duration of Treatment (up to 12 cycles)
Secondary outcomes:
measure: Complete Response Rate in Patients With B-cell Chronic Lymphocytic Leukemia
timeFrame: Duration of Treatment (up to 12 cycles)
measure: Survival Time
timeFrame: Duration of study (up to 2 years)
measure: Progression-free Survival
timeFrame: Duration of study (up to 2 years)
measure: Duration of Response
timeFrame: Duration on study (up 2 years)
Other outcomes:
Locations:
city: Rochester
country: United States
facility: North Central Cancer Treatment Group
state: Minnesota
Study officials:
affiliation: North Central Cancer Treatment Group
name: Tait Shanafelt
role: PRINCIPAL_INVESTIGATOR
References: