NCT01066663

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Mar 2010

Longer than P75 for phase_1

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 9, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 10, 2010

Completed
19 days until next milestone

Study Start

First participant enrolled

March 1, 2010

Completed
11.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2022

Completed
10 months until next milestone

Results Posted

Study results publicly available

December 1, 2022

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2023

Completed
Last Updated

February 22, 2023

Status Verified

January 1, 2023

Enrollment Period

11.9 years

First QC Date

February 9, 2010

Results QC Date

April 4, 2022

Last Update Submit

January 30, 2023

Conditions

Chronic Lymphocytic LeukemiaSmall Lymphocytic Leukemia

Keywords

CLLSLLrelapsedpyrimethamine

Outcome Measures

Primary Outcomes (2)

  • Phase I: Maximum Tolerated Dose (MTD)

    maximum tolerated dose and recommended Phase 2 dose pyrimethamine

    Disease were evaluated weekly in 1st 28 days, and every 2 weeks in 2nd cycle then monthly. Median treatment duration is 1.07 months with range 0.23-9.99 months.

  • Phase II: Overall Response Rate (ORR)

    The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

    Within 10 days of the completion of the cycle required for response evaluation

Secondary Outcomes (2)

  • Incidence of Grade 3 or Higher Treatment-Related Toxicity

    Disease were evaluated weekly in 1st 28 days, and every 2 weeks in 2nd cycle then monthly. Median treatment duration is 1.07 months with range 0.23-9.99 months.

  • Median Progression Free Survival (PFS)

    Disease were evaluated weekly in 1st 28 days, and every 2 weeks in 2nd cycle then monthly, and every 3-6 months during the follow-up.

Study Arms (3)

DL1: Pyrimethamine 12.5 mg

EXPERIMENTAL

Pyrimethamine single daily oral 12.5 mg dose.

Drug: pyrimethamine

DL2: Pyrimethamine 25 mg

EXPERIMENTAL

Pyrimethamine single daily oral 25 mg dose.

Drug: pyrimethamine

DL3: Pyrimethamine 50 mg

EXPERIMENTAL

Pyrimethamine single daily oral 50 mg dose.

Drug: pyrimethamine

Interventions

pyrimethamineDRUG

Taken orally once a day

Also known as: daraprim
DL1: Pyrimethamine 12.5 mgDL2: Pyrimethamine 25 mgDL3: Pyrimethamine 50 mg

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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.

You may not qualify if:

  • 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
  • Uncontrolled intercurrent illness
  • Pregnant or breastfeeding women
  • HIV-positive individuals on combination antiretroviral therapy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-CellRecurrence

Interventions

Pyrimethamine

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
Jennifer R Brown MD PhD
Organization
Dana-Farber Cancer Institute
Jennifer_Brown@dfci.harvard.edu
l 617-632-4894

Study Officials

  • Jennifer Brown, MD, PhD

    Dana-Farber Cancer Institute

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor of Medicine

Study Record Dates

First Submitted

February 9, 2010

First Posted

February 10, 2010

Study Start

March 1, 2010

Primary Completion

February 1, 2022

Study Completion

January 1, 2023

Last Updated

February 22, 2023

Results First Posted

December 1, 2022

Record last verified: 2023-01

Locations

US(2)