Phase 2
N=16
Pyrimethamine for the Treatment of Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia · Small Lymphocytic Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT01066663 ↗Enrolled (actual)
16
Serious AEs
56.3%
Results posted
Dec 2022
Primary outcome: Primary: Phase I: Maximum Tolerated Dose (MTD) — NA mg
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- pyrimethamine (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Dana-Farber Cancer Institute
- Primary completion
- Feb 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase I: Maximum Tolerated Dose (MTD) |
NA | — |
| PRIMARY Phase II: Overall Response Rate (ORR) |
— | — |
| SECONDARY Incidence of Grade 3 or Higher Treatment-Related Toxicity |
1; 5; 8 | — |
| SECONDARY Median Progression Free Survival (PFS) |
1.116; 3.677; 0.969 | — |
Summary
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.
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
Data sourced from ClinicalTrials.gov (NCT01066663). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.