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

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ClinicalTrials.gov Identifier: NCT03989466
Recruitment Status : Not yet recruiting
First Posted : June 18, 2019
Last Update Posted : September 17, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
Recurrent T-Cell Prolymphocytic Leukemia T-Cell Prolymphocytic Leukemia Biological: Alemtuzumab Drug: Itacitinib Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib Pilot Study of Itacitinib With Alemtuzumab in Patients With T-Cell Prolymphocytic Leukemia (T-PLL)
Estimated Study Start Date : October 31, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia
Drug Information available for: Alemtuzumab

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.

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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a diagnosis of T-cell prolymphocytic leukemia (T-PLL) will be eligible (both treatment naive and relapsed patients are eligible).
  • 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.
  • Bilirubin =< 2 mg/dL.
  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) or =< 5 x ULN if related to leukemic involvement).
  • Creatinine =< 1.5 x ULN.
  • Known cardiac ejection fraction of >= 45% within the past 3 months.
  • Eastern Cooperative Oncology Group (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:

  • Pregnant women are excluded from this study because the agent used in this study has the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.
  • Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patient with documented hypersensitivity to any of the components of the therapy program.
  • Patients with known active, uncontrolled central nervous system (CNS) leukemia will not be eligible.
  • Patients with prior treatment with a JAK1, JAK2, or JAK3 inhibitor will not be eligible.
  • Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.
  • Known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies).
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment or at risk for HBV reactivation. Hepatitis B virus deoxyribonucleic acid (DNA) and HCV ribonucleic acid (RNA) must be undetectable upon testing. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive. Prior test results obtained as part of standard of care that confirm a subject is immune and not at risk for reactivation (ie, hepatitis B surface antigen negative, surface antibody positive) may be used for purposes of eligibility and tests do not need to be repeated. Subjects with prior positive serology results must have negative polymerase chain reaction results. Subjects whose immune status is unknown or uncertain must have results confirming immune status before enrollment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03989466


Contacts
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Contact: Tapan Kadia 713-563-3534 tkadia@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Tapan M. Kadia    713-563-3534      
Principal Investigator: Tapan M. Kadia         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Tapan M Kadia M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03989466     History of Changes
Other Study ID Numbers: 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 )
First Posted: June 18, 2019    Key Record Dates
Last Update Posted: September 17, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Prolymphocytic
Leukemia, Prolymphocytic, T-Cell
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, T-Cell
Antineoplastic Agents, Immunological
Alemtuzumab
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents