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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Dana-Farber Cancer Institute
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
ClinicalTrials.gov Identifier:
NCT01066663
First received: February 9, 2010
Last updated: June 23, 2014
Last verified: April 2014
  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.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Small Lymphocytic Leukemia
Drug: pyrimethamine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Pyrimethamine, a STAT3 Inhibitor, for the Treatment of Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Phase I: To determine the maximum tolerated dose and recommended Phase 2 dose of pyrimethamine in relapsed CLL/SLL [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Phase II: To determine the overall response rate of pyrimethamine in relapsed CLL/SLL. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the toxicity profile of pyrimethamine in relapsed CLL/SLL, both acutely and over prolonged daily dosing. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To determine pyrimethamine levels in vivo with prolonged dosing. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To determine the progression-free survival following pyrimethamine for the treatment of relapsed CLL/SLL [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 26
Study Start Date: March 2010
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pyrimethamine
Single daily oral 50 mg dose.
Drug: pyrimethamine
Taken orally once a day

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01066663

Contacts
Contact: Jennifer Brown, MD, PhD 617-632-6692
Contact: Elizabeth Coughlin 617-582-8713

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Robin Joyce, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Jennifer Brown, MD, PhD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Lymphoma Research Foundation
Investigators
Principal Investigator: Jennifer Brown, MD, PhD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Jennifer R. Brown, MD, PhD, Assistant Professor of Medicine, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01066663     History of Changes
Other Study ID Numbers: 09-421
Study First Received: February 9, 2010
Last Updated: June 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
CLL
SLL
relapsed
pyrimethamine

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pyrimethamine
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014