Pyrimethamine for the Treatment of Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Information source: Dana-Farber Cancer Institute
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Chronic Lymphocytic Leukemia; Small Lymphocytic Leukemia
Intervention: pyrimethamine (Drug)
Phase: Phase 1/Phase 2
Sponsored by: Dana-Farber Cancer Institute
Official(s) and/or principal investigator(s):
Jennifer Brown, MD, PhD, Principal Investigator, Affiliation: Dana-Farber Cancer Institute
Jennifer Brown, MD, PhD, Phone: 617-632-6692
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.
Official title: A Phase I/II Study of Pyrimethamine, a STAT3 Inhibitor, for the Treatment of Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Phase I: To determine the maximum tolerated dose and recommended Phase 2 dose of pyrimethamine in relapsed CLL/SLL
Phase II: To determine the overall response rate of pyrimethamine in relapsed CLL/SLL.
To assess the toxicity profile of pyrimethamine in relapsed CLL/SLL, both acutely and over prolonged daily dosing.
To determine pyrimethamine levels in vivo with prolonged dosing.
To determine the progression-free survival following pyrimethamine for the treatment of relapsed CLL/SLL
- 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.
Minimum age: 18 Years.
Maximum age: N/A.
- 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 >
- 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.
- 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
Locations and Contacts
Jennifer Brown, MD, PhD, Phone: 617-632-6692
Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States; Recruiting
Jennifer Brown, MD, PhD, Principal Investigator
Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, United States; Recruiting
Robin Joyce, MD, Principal Investigator
Starting date: March 2010
Last updated: November 30, 2012