- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03989466
Itacitinib and Alemtuzumab in Treating Patients With T-Cell Prolymphocytic Leukemia
Phase Ib Pilot Study of Itacitinib With Alemtuzumab in Patients With T-Cell Prolymphocytic Leukemia (T-PLL)
Study Overview
Status
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of itacitinib in combination with alemtuzumab in patients with T-cell prolymphocytic leukemia (T-PLL).
SECONDARY OBJECTIVES:
I. To evaluate the event free survival (EFS) in patients (pts) with T-PLL treated with itacitinib in combination with alemtuzumab.
II. To evaluate response complete remission (CR), complete remission without blood count recovery (CRi), or partial remission (PR) (CR/CRi or PR) of itacitinib in combination with alemtuzumab in patients with T-PLL.
III. To explore the single-agent activity of itacitinib in pts with T-PLL. IV. To assess the time to response, response duration, and overall survival (OS) in pts with T-PLL treated with the combination of itacitinib and alemtuzumab.
EXPLORATORY OBJECTIVES:
I. To explore the effect of itacitinib on STAT5 phosphorylation in pts with T-PLL II. To explore the association of pretreatment somatic mutations and the dynamics of STAT5 phosphorylation with response.
OUTLINE: This is a dose-escalation study of alemtuzumab.
CYCLE 1: Patients receive itacitinib orally (PO) once daily (QD) on days 1-28 and alemtuzumab intravenously (IV) over 2 hours on days 15, 17, 19, 21, 23, 25, and 27 in the absence of disease progression of unacceptable toxicity.
CYCLE 2 AND BEYOND: Patients receive itacitinib PO QD on day 1-28 and alemtuzumab IV over 2 hours on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, and 27. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients who achieve a response (CR/CRi or PR) may receive itacitinib for up to 8 additional cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients with a diagnosis of T-cell prolymphocytic leukemia (T-PLL) will be eligible (both treatment naïve and relapsed patients are eligible).
- Age >/= 18 years.
- Patients must not have had chemotherapy or antibody therapy for 7 days prior to starting ITACITINIB. However, patients with rapidly proliferative disease may receive hydroxyurea or decadron until 24 hours prior to starting therapy on this protocol.
- Adequate organ function as defined below: liver function (bilirubin </=2mg/dL, AST and ALT </=3 x ULN or </=5 x ULN if related to leukemic involvement); kidney function (estimated creatinine clearance > 50); known cardiac ejection fraction of > or = 45% within the past 3 months; and platelet count </=30,000.
- ECOG performance status of </= 2.
- A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
- Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol.
Exclusion Criteria:
- Patients with a diagnosis of T-cell prolymphocytic leukemia (T-PLL) will be eligible (both treatment naïve and relapsed patients are eligible).
- Age >/= 18 years.
- Patients must not have had chemotherapy or antibody therapy for 7 days prior to starting ITACITINIB. However, patients with rapidly proliferative disease may receive hydroxyurea or decadron until 24 hours prior to starting therapy on this protocol.
- Adequate organ function as defined below: liver function (bilirubin </=2mg/dL, AST and ALT </=3 x ULN or </=5 x ULN if related to leukemic involvement); kidney function (estimated creatinine clearance > 50); known cardiac ejection fraction of > or = 45% within the past 3 months; and platelet count </=30,000.
- ECOG performance status of </= 2.
- A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
- Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (itacitinib, alemtuzumab)
CYCLE 1: Patients receive itacitinib PO QD on days 1-28 and alemtuzumab IV over 2 hours on days 15, 17, 19, 21, 23, 25, and 27 in the absence of disease progression of unacceptable toxicity. CYCLE 2 AND BEYOND: Patients receive itacitinib PO QD on day 1-28 and alemtuzumab IV over 2 hours on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, and 27. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients who achieve a response (CR/CRi or PR) may receive itacitinib for up to 8 additional cycles in the absence of disease progression or unacceptable toxicity. |
Given PO
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events (AEs)
Time Frame: Up to 2 years
|
The severity of the toxicities will be graded according to the latest version of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
The number and percent of subjects with treatment-emergent adverse events will be summarized according to intensity and drug relationship, and categorized by System Organ Class and preferred term by dose level/Part.
All reported AEs that occur after signing informed consent will be included in the analysis of all reported AEs.
Exposure to study drug and reasons for discontinuation of study drug will be tabulated.
Data will be summarized using descriptive statistics.
Continuous variables will be summarized using the number of observations, mean, standard deviation, coefficient of variation, median, and range as appropriate.
Categorical values will be summarized using the number of observations and percentages as appropriate.
|
Up to 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response rate (complete remission[CR], complete remission without blood count recovery [CRi], or partial remission [PR])
Time Frame: Up to 2 years
|
The response rate (CR/CRi or PR) will be estimated for all patients along with the 95% confidence interval.
Patients with missing or no response assessments will be classified as non-responders.
The association between response and patient and clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test.
The response rate will be compared between different subgroups (e.g.
mutation types) by Fisher exact test.
|
Up to 2 years
|
Duration of response (DOR)
Time Frame: From the first documented onset of PR or CR/CRi to the date of progressive disease/relapse or death due to underlying disease, assessed up to 2 years
|
Listed and summarized by the Kaplan-Meier estimator.
|
From the first documented onset of PR or CR/CRi to the date of progressive disease/relapse or death due to underlying disease, assessed up to 2 years
|
Time to response
Time Frame: Up to 2 years
|
Listed and summarized by the Kaplan-Meier estimator.
Time to response is defined as the time from treatment start till response (CR/CRi/PR) or last follow-up.
|
Up to 2 years
|
Overall survival
Time Frame: From treatment till death or last follow-up, assessed up to 2 years
|
Listed and summarized by the Kaplan-Meier estimator.
|
From treatment till death or last follow-up, assessed up to 2 years
|
Event-free survival
Time Frame: From start of treatment to the date of event defined as the first documented progressive disease/relapse, or death due to any cause, whichever comes first, assessed up to 2 years
|
Listed and summarized by the Kaplan-Meier estimator.
Logrank test will be used to compare the time-to-event difference between different subgroups.
|
From start of treatment to the date of event defined as the first documented progressive disease/relapse, or death due to any cause, whichever comes first, assessed up to 2 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Tapan M Kadia, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia, Lymphoid
- Leukemia, T-Cell
- Leukemia
- Leukemia, Prolymphocytic
- Leukemia, Prolymphocytic, T-Cell
- Physiological Effects of Drugs
- Antineoplastic Agents
- Immunologic Factors
- Antibodies
- Immunoglobulins
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- Alemtuzumab
Other Study ID Numbers
- 2019-0054 (Other Identifier: M D Anderson Cancer Center)
- NCI-2019-03203 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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