Trial Outcomes & Findings for Pyrimethamine for the Treatment of Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (NCT NCT01066663)

NCT ID: NCT01066663

Last Updated: 2023-02-22

Results Overview

maximum tolerated dose and recommended Phase 2 dose pyrimethamine

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

20 participants

Primary outcome timeframe

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.

Results posted on

2023-02-22

Participant Flow

from May 2010 to April 2012

Participant milestones

Participant milestones
Measure	DL1: Pyrimethamine 12.5 mg Pyrimethamine single daily oral 12.5 mg dose.	DL2: Pyrimethamine 25 mg Pyrimethamine single daily oral 25 mg dose.	DL3: Pyrimethamine 50 mg Pyrimethamine single daily oral 50 mg dose.
Overall Study STARTED	3	3	10
Overall Study COMPLETED	3	3	9
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	DL1: Pyrimethamine 12.5 mg Pyrimethamine single daily oral 12.5 mg dose.	DL2: Pyrimethamine 25 mg Pyrimethamine single daily oral 25 mg dose.	DL3: Pyrimethamine 50 mg Pyrimethamine single daily oral 50 mg dose.
Overall Study Adverse Event	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DL1: Pyrimethamine 12.5 mg n=3 Participants Pyrimethamine single daily oral 12.5 mg dose.	DL2: Pyrimethamine 25 mg n=3 Participants Pyrimethamine single daily oral 25 mg dose.	DL3: Pyrimethamine 50 mg n=10 Participants Pyrimethamine single daily oral 50 mg dose.	Total n=16 Participants Total of all reporting groups
Age, Continuous	53 years n=5 Participants	54 years n=7 Participants	60 years n=5 Participants	56 years n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants
Race/Ethnicity, Customized White	2 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants	14 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

maximum tolerated dose and recommended Phase 2 dose pyrimethamine

Outcome measures

Outcome measures
Measure	Pyrimethamine Phase 1 (Dose-escalation) n=16 Participants Pyrimethamine single daily oral 12.5 mg. 25 mg, or 50 mg dose for dose escalation to determine the MTD	DL2: Pyrimethamine 25 mg Pyrimethamine single daily oral 25 mg dose.	DL3: Pyrimethamine 50 mg Pyrimethamine single daily oral 50 mg dose.
Phase I: Maximum Tolerated Dose (MTD)	NA mg too few dose limiting toxicities so it is not statistically detectable	—	—

PRIMARY outcome

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

Population: The phase 2 study were not done and data not collected

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

All grade 3 or higher adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAE as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 3 or higher AE of any type during the time of observation.

Outcome measures

Outcome measures
Measure	Pyrimethamine Phase 1 (Dose-escalation) n=3 Participants Pyrimethamine single daily oral 12.5 mg. 25 mg, or 50 mg dose for dose escalation to determine the MTD	DL2: Pyrimethamine 25 mg n=3 Participants Pyrimethamine single daily oral 25 mg dose.	DL3: Pyrimethamine 50 mg n=10 Participants Pyrimethamine single daily oral 50 mg dose.
Incidence of Grade 3 or Higher Treatment-Related Toxicity	1 number of new cases per 1000 person year	5 number of new cases per 1000 person year	8 number of new cases per 1000 person year

SECONDARY outcome

Timeframe: 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.

Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

Outcome measures

Outcome measures
Measure	Pyrimethamine Phase 1 (Dose-escalation) n=3 Participants Pyrimethamine single daily oral 12.5 mg. 25 mg, or 50 mg dose for dose escalation to determine the MTD	DL2: Pyrimethamine 25 mg n=3 Participants Pyrimethamine single daily oral 25 mg dose.	DL3: Pyrimethamine 50 mg n=10 Participants Pyrimethamine single daily oral 50 mg dose.
Median Progression Free Survival (PFS)	1.116 months Interval 0.46 to Upper confidence interval not statistically reachable	3.677 months Interval 2.791 to Upper confidence interval not statistically reachable	0.969 months Interval 0.591 to Upper confidence interval not statistically reachable

Adverse Events

DL1: Pyrimethamine 12.5 mg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

DL2: Pyrimethamine 25 mg

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

DL3: Pyrimethamine 50 mg

Serious events: 6 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	DL1: Pyrimethamine 12.5 mg n=3 participants at risk Pyrimethamine single daily oral 12.5 mg dose.	DL2: Pyrimethamine 25 mg n=3 participants at risk Pyrimethamine single daily oral 25 mg dose.	DL3: Pyrimethamine 50 mg n=10 participants at risk Pyrimethamine single daily oral 50 mg dose.
Blood and lymphatic system disorders Anemia	0.00% 0/3 • AE 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.	33.3% 1/3 • AE 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.	0.00% 0/10 • AE 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.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	0.00% 0/3 • AE 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.	33.3% 1/3 • AE 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.	0.00% 0/10 • AE 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.
Investigations Blood gonadotrophin abnormal	0.00% 0/3 • AE 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.	0.00% 0/3 • AE 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.	10.0% 1/10 • AE 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.
Blood and lymphatic system disorders Hemolysis	0.00% 0/3 • AE 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.	0.00% 0/3 • AE 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.	10.0% 1/10 • AE 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.
Metabolism and nutrition disorders Hyperuricemia	0.00% 0/3 • AE 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.	0.00% 0/3 • AE 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.	10.0% 1/10 • AE 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.
Investigations Neutrophil count decreased	0.00% 0/3 • AE 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.	66.7% 2/3 • AE 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.	30.0% 3/10 • AE 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.
Investigations Platelet count decreased	33.3% 1/3 • AE 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.	33.3% 1/3 • AE 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.	30.0% 3/10 • AE 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.
Investigations White blood cell decreased	0.00% 0/3 • AE 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.	33.3% 1/3 • AE 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.	10.0% 1/10 • AE 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.

Other adverse events

Additional Information

Jennifer R Brown MD PhD

Dana-Farber Cancer Institute

Phone: l 617-632-4894

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place