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

NCT03989466 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2019-0054NCI-2019-03203
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent T-Cell Prolymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events (AEs)

  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 Outcomes (5)

• Response rate (complete remission[CR], complete remission without blood count recovery [CRi], or partial remission [PR])

  Up to 2 years

• Duration of response (DOR)

  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

  Up to 2 years

• Overall survival

  From treatment till death or last follow-up, assessed up to 2 years

• Event-free survival

  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

Study Arms (1)

Treatment (itacitinib, alemtuzumab)

EXPERIMENTAL

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; Drug: Itacitinib

Interventions

Alemtuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD52 Monoclonal Antibody, Campath, Campath-1H, LDP-03, Lemtrada, MabCampath, Monoclonal Antibody Campath-1H

Treatment (itacitinib, alemtuzumab)

Itacitinib DRUG

Given PO

Also known as: INCB 039110, INCB-039110, INCB039110

Treatment (itacitinib, alemtuzumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Kadia TM, Jain A, Rausch CR, Bataller A, Ravandi F, Jabbour E, Qiao W, Borthakur G, Short N, Montalban-Bravo G, Quesada AE, Burger J, Ferrajoli A, Wierda W, Hosing C, Kantarjian H. Phase 1B pilot study of itacitinib with alemtuzumab in patients with T-cell prolymphocytic leukemia. Blood Neoplasia. 2025 Oct 24;3(1):100175. doi: 10.1016/j.bneo.2025.100175. eCollection 2026 Feb.

  PMID: 41536780 DERIVED

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Prolymphocytic, T-Cell

Interventions

Alemtuzumab; itacitinib; INCB039110

Condition Hierarchy (Ancestors)

Leukemia, Prolymphocytic; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Leukemia, T-Cell; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Tapan M Kadia

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2019
• First Posted: June 18, 2019
• Study Start: January 15, 2020
• Primary Completion: September 24, 2024
• Study Completion: September 24, 2024
• Last Updated: October 10, 2024

Record last verified: 2024-10

Locations

US (1)