Dual PD-1 and JAK2 Inhibition in Hematological Malignancies

NCT04016116 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 17-01435
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Pembrolizumab will have significant clinical activity in patients with Intermediate and high risk MF, advanced PV who have been resistant, failed or are intolerant to JAK2 inhibitor therapy and the activity may be enhanced in combination with JAK2 inhibition by Ruxolitinib; similarly MDS/MPN and CMML patients for who no standard therapies are available will exhibit responses to PD-1 or dual JAK2 and PD-1 treatment. Adding JAK2 inhibitor Ruxolitinib to Pembrolizumab will have significant activity in patients with advanced, progressive HL who failed single agent PD-1 inhibition.

Conditions

Cancer; Hematological Malignancy

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) measured using the Kaplan-Meier Method

  Progression free survival (PFS) is defined as the time from randomization or enrollment registration to the earliest date of documentation of disease progression or death.

  6 Months

Study Arms (3)

Pembrolizumab (Cohort 1)

EXPERIMENTAL

Pembrolizumab IV every 3 weeks (Cohort 1: Advanced progressive MPNs)

Drug: Pembrolizumab

Pembrolizumab + Ruxolitinib

EXPERIMENTAL

Pembrolizumab IV every 3 weeks \& Ruxolitinib po days 1-21 (Cohort 1: Advanced progressive MPNs)

Drug: Pembrolizumab; Drug: Ruxolitinib

Pembrolizumab + Ruxolitinib (Cohort 2)

EXPERIMENTAL

Pembrolizumab IV every 3 weeks \& Ruxolitinib po days 1-21 (Cohort 2, unresponsive to PD-1)

Drug: Pembrolizumab; Drug: Ruxolitinib

Interventions

Pembrolizumab DRUG

Pembrolizumab IV every 3 weeks

Also known as: keytruda

Pembrolizumab (Cohort 1); Pembrolizumab + Ruxolitinib; Pembrolizumab + Ruxolitinib (Cohort 2)

Ruxolitinib DRUG

Ruxolitinib po days 1-21

Also known as: jakafi

Pembrolizumab + Ruxolitinib; Pembrolizumab + Ruxolitinib (Cohort 2)

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• advanced progressive MPNs, defined as intermediate and high risk MF or advanced PV resistant, failed or intolerant to JAK2 inhibitor therapy requiring medical therapy and patients with MDS/MPN Overlap and CMML having failed or for whom there are no standard therapies are available, are eligible. Patients will be allocated to one of two treatment arms:
• Pembrolizumab
• Pembrolizumab plus JAK2 inhibitor Ruxolitinib
• Patients with relapsed\* or refractory\* Hodgkin lymphoma (HL) who progress on PD-1 inhibitory treatment after achieving a partial response (PR) or complete response (CR) or stable disease (SD) or who are non-responsive to PD-1 inhibitory therapy. Patients must have failed appropriate standard treatment options.
• Relapsed: disease progression after most recent therapy
• Refractory: failure to achieve CR or PR to most recent therapy
• The following laboratory values obtained less than 7 days prior to registration.
• Total bilirubin ≤ 1.5 x Upper Limit normal (ULN) (except Gilbert's syndrome or known hemolysis or leukemic infiltration)
• AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN or \< 5 x ULN if organ involvement
• Alkaline Phosphatase \< 5 x ULN
• Serum creatinine ≤ 2 x ULN or 24 hour Cr clearance \>60ml/min
• MPN: -Platelet count ≥50,000/μL; Absolute neutrophil count (ANC) ≥250/μL
• MPN: -Platelet count ≥50,000/μL ;Absolute neutrophil count (ANC) ≥250/μL
• MDS/MPN Overlap, CMML: Platelet count ≥25,000/μL; Absolute neutrophil count (ANC) ≥250/μ
• HL-Platelet count ≥75,000/μL; Absolute neutrophil count (ANC) ≥1000/μL (800/ μL if marrow disease involvement; ECOG Performance Status (PS) 0 or 1 (Appendix I)

You may not qualify if:

• Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements.
• Any of the following prior therapies:
• Cytotoxic Chemotherapy less than 14 days prior to registration
• Immunotherapy less than 14 days prior to registration
• Biologic therapy (i.e. antibody therapies) less than 28 days prior to registration (see also 3.32)
• Radiation therapy less than 14 days prior to registration
• Targeted therapies (i.e. kinase inhibitors, less than 7 days or 5 half-life's whichever is shorter)
• Hydroxyurea (HU) is allowed for blast count control throughout study
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm ≤ 14 days prior to registration
• Active uncontrolled CNS leukemia. NOTE: Positive (cyto)pathology is allowed and patient can receive intrathecal chemotherapy
• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy.
• Hypersensitivity to Ruxolitinib or any of its excipients.
• Acute Myeloid Leukemia with \> 30% blasts in the bone marrow of peripheral blood
• Major surgery ≤ 28 days prior to treatment
• Clinically significant heart disease

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

New York University School of Medicine

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Neoplasms; Hematologic Neoplasms

Interventions

pembrolizumab; ruxolitinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Raoul Tibes, MD

  New York Langone Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2019
• First Posted: July 11, 2019
• Study Start: December 1, 2019
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2021
• Last Updated: May 27, 2020

Record last verified: 2020-05

Locations

US (1)