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Itacitinib and Alemtuzumab in Treating Patients With T-Cell Prolymphocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03989466
Recruitment Status : Recruiting
First Posted : June 18, 2019
Last Update Posted : January 21, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE June 14, 2019
First Posted Date  ICMJE June 18, 2019
Last Update Posted Date January 21, 2020
Actual Study Start Date  ICMJE January 15, 2020
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 14, 2019)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2019)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
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 Itacitinib and Alemtuzumab in Treating Patients With T-Cell Prolymphocytic Leukemia
Official Title  ICMJE Phase Ib Pilot Study of Itacitinib With Alemtuzumab in Patients With T-Cell Prolymphocytic Leukemia (T-PLL)
Brief Summary This phase Ib trial studies the side effects and best dose of alemtuzumab when given together with itacitinib in treating patients with T-cell prolymphocytic leukemia. Itacitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with alemtuzumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving itacitinib and alemtuzumab may work better in treating patients with T-cell prolymphocytic leukemia compared to standard of care 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent T-Cell Prolymphocytic Leukemia
  • T-Cell Prolymphocytic Leukemia
Intervention  ICMJE
  • Biological: Alemtuzumab
    Given IV
    Other Names:
    • Anti-CD52 Monoclonal Antibody
    • Campath
    • Campath-1H
    • LDP-03
    • Lemtrada
    • MabCampath
    • Monoclonal Antibody Campath-1H
  • Drug: Itacitinib
    Given PO
    Other Names:
    • INCB 039110
    • INCB-039110
    • INCB039110
Study Arms  ICMJE 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.

Interventions:
  • Biological: Alemtuzumab
  • Drug: Itacitinib
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: June 14, 2019)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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: Tapan Kadia 713-563-3534 tkadia@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03989466
Other Study ID Numbers  ICMJE 2019-0054
NCI-2019-03203 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2019-0054 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Tapan M Kadia M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date January 2020

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