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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia

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Trial Information

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

- 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.

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

- 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

- 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

- Uncontrolled intercurrent illness

- Pregnant or breastfeeding women

- HIV-positive individuals on combination antiretroviral therapy

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phase I: To determine the maximum tolerated dose and recommended Phase 2 dose of pyrimethamine in relapsed CLL/SLL

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Jennifer Brown, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute


United States: Institutional Review Board

Study ID:




Start Date:

March 2010

Completion Date:

Related Keywords:

  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Leukemia
  • CLL
  • SLL
  • relapsed
  • pyrimethamine
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma



Beth Israel Deaconess Medical Center Boston, Massachusetts  02215
Dana-Farber Cancer Institute Boston, Massachusetts  02115