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

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ClinicalTrials.gov Identifier: NCT01066663
Recruitment Status : Recruiting
First Posted : February 10, 2010
Last Update Posted : January 6, 2020
Sponsor:
Collaborators:
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Lymphoma Research Foundation
Information provided by (Responsible Party):
Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute

Tracking Information
First Submitted Date  ICMJE February 9, 2010
First Posted Date  ICMJE February 10, 2010
Last Update Posted Date January 6, 2020
Actual Study Start Date  ICMJE March 2010
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 9, 2010)
  • Phase I: To determine the maximum tolerated dose and recommended Phase 2 dose of pyrimethamine in relapsed CLL/SLL [ Time Frame: 1 year ]
  • Phase II: To determine the overall response rate of pyrimethamine in relapsed CLL/SLL. [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 9, 2010)
  • To assess the toxicity profile of pyrimethamine in relapsed CLL/SLL, both acutely and over prolonged daily dosing. [ Time Frame: 2 years ]
  • To determine pyrimethamine levels in vivo with prolonged dosing. [ Time Frame: 2 years ]
  • To determine the progression-free survival following pyrimethamine for the treatment of relapsed CLL/SLL [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pyrimethamine for the Treatment of Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Official Title  ICMJE A Phase I/II Study of Pyrimethamine, a STAT3 Inhibitor, for the Treatment of Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Brief 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Leukemia
Intervention  ICMJE Drug: pyrimethamine
Taken orally once a day
Other Name: daraprim
Study Arms  ICMJE Experimental: Pyrimethamine
Single daily oral 50 mg dose.
Intervention: Drug: pyrimethamine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 9, 2010)
26
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2024
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jennifer Brown, MD, PhD 617-632-4165
Contact: Kalin Goldstone, MD, PhD 617-582-8713 Kalin_Goldstone@DFCI.HARVARD.EDU
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01066663
Other Study ID Numbers  ICMJE 09-421
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute
Study Sponsor  ICMJE Dana-Farber Cancer Institute
Collaborators  ICMJE
  • Brigham and Women's Hospital
  • Beth Israel Deaconess Medical Center
  • Lymphoma Research Foundation
Investigators  ICMJE
Principal Investigator: Jennifer Brown, MD, PhD Dana-Farber Cancer Institute
PRS Account Dana-Farber Cancer Institute
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP