Clinical Trials /

Pyrimethamine for the Treatment of Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

NCT01066663

Description:

In this research study we will start by looking for the highest dose of pyrimethamine that can be given safely to CLL patients without severe or unmanageable side effects. This dose will then be used for a larger Phase II study to assess the efficacy of pyrimethamine for the treatment of CLL/SLL. Pyrimethamine is an antibiotic that is used for the treatment of certain infections. Previous research studies have shown that pyrimethamine may target a protein in tumor cells, called STAT3, which may be important for the growth of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) cells. Pyrimethamine can kill CLL/SLL cells in the laboratory, and we are therefore undertaking this study to assess whether pyrimethamine will result in clinical benefit or tumor responses in CLL in patients.

Related Conditions:
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pyrimethamine for the Treatment of Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
  • Official Title: A Phase I/II Study of Pyrimethamine, a STAT3 Inhibitor, for the Treatment of Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 09-421
  • NCT ID: NCT01066663

Conditions

  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Leukemia

Interventions

DrugSynonymsArms
pyrimethaminePyrimethamine

Purpose

In this research study we will start by looking for the highest dose of pyrimethamine that can be given safely to CLL patients without severe or unmanageable side effects. This dose will then be used for a larger Phase II study to assess the efficacy of pyrimethamine for the treatment of CLL/SLL. Pyrimethamine is an antibiotic that is used for the treatment of certain infections. Previous research studies have shown that pyrimethamine may target a protein in tumor cells, called STAT3, which may be important for the growth of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) cells. Pyrimethamine can kill CLL/SLL cells in the laboratory, and we are therefore undertaking this study to assess whether pyrimethamine will result in clinical benefit or tumor responses in CLL in patients.

Detailed Description

      -  Participants will be required to enroll in DFCI Protocol 99-224, the CLL Research
           Consortium Tissue Bank, and DFCI Protocol 01-206, Tissue and Data Collection for
           Research Studies in Patients with Hematologic Malignancies, Bone Marrow Disorders, and
           Normal Donors, or may have blood banked for future use.

        -  Each treatment cycle lasts 28 days during which time participants will take
           pyrimethamine orally once per day. Since we are looking for the highest dose of the
           study drug that can be administered safely without severe or unmanageable side effects,
           not everyone who participates will receive the same dose of study drug.

        -  The following tests and procedures will be performed at specific time points during
           participation in the study: Physical exam, vital signs, blood tests and bone marrow
           biopsy. The participant's tumor will be assessed by CT scans of the chest, abdomen and
           pelvis prior to the start of the study and at the end of the 1st, 3rd and 6th months.

        -  Participants can continue to receive pyrimethamine as long as they do not have side
           effects and their disease does not worsen.
    

Trial Arms

NameTypeDescriptionInterventions
PyrimethamineExperimentalSingle daily oral 50 mg dose.
  • pyrimethamine

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosed with CLL/SLL based on the standard histologic and immunophenotypic criteria
             described in the WHO classification of lymphoid malignancies, including
             immunophenotypic confirmation that the tumor cells co-express B cell antigens CD19/20
             and CD5. Mantle cell lymphoma should be excluded based on positive staining of the
             tumor cells for CD23, or the absence of staining of the tumor cells for cyclin D1 or
             the absence of t(11;14). This diagnosis should be confirmed at a Dana-Farber/Harvard
             Cancer Center institution within approximately one month after the subject is
             registered.

          -  Measurable disease, defined as lymphocytosis > 5,000/uL, or at least one palpable or
             CT measurable lesion > approximately 1.5cm, or bone marrow involvement > approximately
             30%

          -  Relapsed after at least one prior purine analogue-containing regimen, or at least two
             non-purine analogue containing regimens

          -  18 years of age or older

          -  Life expectancy of greater than 3 months

          -  ECOG performance status of 0, 1 or 2

          -  Normal organ function as outlined in the protocol

          -  Require treatment based on IWCLL 2008 criteria

          -  Women of child-bearing potential and men must agree to use adequate contraception
             prior to study entry and for the duration of study participation.

        Exclusion Criteria:

          -  Chemotherapy or radiotherapy within 3 weeks prior to entering the study or those who
             have not recovered from clinically significant adverse events due to agents
             administered more than 3 weeks earlier.

          -  May not be receiving any other study agents

          -  Known CNS involvement with CLL

          -  History of allergic reactions or sensitivity to pyrimethamine

          -  Patients taking folic acid are eligible if the folic acid is discontinued prior to
             pyrimethamine administration and not taken for the duration of time enrolled on this
             study

          -  Prior allogeneic SCT is an exclusion only if the subject has active graft vs. host
             disease or requires immunosuppression other than a constant stable dose of
             glucocorticoids

          -  Uncontrolled intercurrent illness

          -  Pregnant or breastfeeding women

          -  HIV-positive individuals on combination antiretroviral therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: To determine the maximum tolerated dose and recommended Phase 2 dose of pyrimethamine in relapsed CLL/SLL
Time Frame:1 year
Safety Issue:
Description:

Secondary Outcome Measures

Measure:To assess the toxicity profile of pyrimethamine in relapsed CLL/SLL, both acutely and over prolonged daily dosing.
Time Frame:2 years
Safety Issue:
Description:
Measure:To determine pyrimethamine levels in vivo with prolonged dosing.
Time Frame:2 years
Safety Issue:
Description:
Measure:To determine the progression-free survival following pyrimethamine for the treatment of relapsed CLL/SLL
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • CLL
  • SLL
  • relapsed
  • pyrimethamine

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