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Trial record 1 of 1 for:    NKTR-255
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NKTR-255 in Relapsed/Refractory Multiple Myeloma & Non-Hodgkin Lymphoma

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ClinicalTrials.gov Identifier: NCT04136756
Recruitment Status : Recruiting
First Posted : October 23, 2019
Last Update Posted : June 16, 2020
Sponsor:
Information provided by (Responsible Party):
Nektar Therapeutics

Brief Summary:

Patients will receive intravenous NKTR-255 in 21-day treatment cycles. During the Part 1 dose escalation portion of the trial, NKTR-255 will be given as monotherapy. After determination of the recommended Phase 2 dose (RP2D) of NKTR-255, NKTR-255 will be evaluated in 3 expansion Cohorts in Part 2. Cohort A will enroll Non-Hodgkin Lymphoma (NHL) patients that have relapsed after CAR-T therapy. Cohort B will enroll patients with relapsed/refractory Multiple Myeloma (MM). Cohort C will enroll patients with relapsed/refractory indolent Non-Hodgkin Lymphoma (iNHL).

This is a Phase 1 study to evaluate safety and tolerability of NKTR-255 alone and in combination with daratumumab or rituximab.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Non-Hodgkin Lymphoma Indolent Non-Hodgkin Lymphoma Drug: NKTR-255 Drug: Daratumumab Drug: Rituximab Phase 1

Detailed Description:

NKTR-255 is a cytokine that is designed to regulate T and natural killer cell activation, proliferation and promote their anti-tumor effects.

This is a Phase 1, open-label, multi-center, dose escalation, dose expansion, safety follow-up, and survival follow-up of NKTR-255 as a single agent and NKTR-255 in combination with daratumumab or ritixumab. Study treatment is defined as any investigational treatment(s) or marketed product(s), intended to be administered to a study patient according to the study enrollment.

Part 1 will enroll relapsed/refractory MM and NHL patients. In Part 2, Cohort A will enroll NHL patients who have progressed on a chimeric antigen receptor T-cell (CAR-T) product, Cohort B will enroll MM patients who previously received daratumumab and other anti-CD38 therapies to receive NKTR-255 alone and/or in combination with daratumumab, and Cohort C will enroll iNHL patients who previously received rituximab and other therapies to receive NKTR-255 alone and/or in combination with rituximab.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 87 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-label, Multi-center, Dose Escalation and Dose Expansion Study of NKTR-255 as a Single Agent in Relapsed or Refractory Hematological Malignancies
Actual Study Start Date : October 7, 2019
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : October 2023


Arm Intervention/treatment
Experimental: Dose Escalation of NKTR-255
Patients will receive intravenous (IV) NKTR-255 every 21 days (q21d) to establish RP2D.
Drug: NKTR-255
NKTR-255 administered by intravenous infusion (IV) every 21 days to establish safety and tolerability

Experimental: Dose Expansion of NKTR-255 alone
The selected RP2D of NKTR-255 will be evaluated in expansion cohorts. Cohort A in patients with relapsed NHL after CAR-T therapy as a salvage regimen to further characterize safety and tolerability. Cohort B1 will evaluate NKTR-255 in patients with MM with progressive disease who have had at least 3 prior lines of therapy treatment. Cohort C1 will evaluate patients with iNHL that has progressed during or following 1 or more prior systemic rituximab-containing (or another treatment with an anti-CD20 antibody-containing) regimens for lymphoma.
Drug: NKTR-255
NKTR-255 administered by intravenous infusion (IV) every 21 days to establish safety and tolerability

Experimental: Dose Expansion of NKTR-255 with Daratumumab
The selected RP2D of NKTR-255 will be evaluated in expansion Cohort B2, which will combine NKTR-255 with daratumumab in patients with MM with progressive disease who have had at least 3 prior lines of therapy treatment.
Drug: NKTR-255
NKTR-255 administered by intravenous infusion (IV) every 21 days to establish safety and tolerability

Drug: Daratumumab
Daratumumab administered by IV at a dose of 16 mg/kg weekly for 8 weeks, then every 2 weeks for 16 weeks, and then every 4 weeks thereafter
Other Name: Darzalex

Experimental: Dose Expansion of NKTR-255 with Rituximab
The selected RP2D of NKTR-255 will be evaluated in Cohort C2, which will combine NKTR-255 with rituximab in patients with iNHL that has progressed during or following 1 or more prior systemic rituximab-containing (or another treatment with an anti-CD20 antibody-containing) regimens for lymphoma.
Drug: NKTR-255
NKTR-255 administered by intravenous infusion (IV) every 21 days to establish safety and tolerability

Drug: Rituximab
In the induction period, patients will receive IV rituximab 375 mg/m2 given once a week for 4 weeks, combined with 3 doses of NKTR-255 at the selected RP2D (given once every 21 days [q21d] for 3 cycles). Eligible patients (patients who achieve CR/PR or clinical benefit deemed by the Investigator and Medical Monitor) will receive maintenance with 4 additional doses of rituximab administered once every other 28-day cycle in combination with NKTR-255 q28d.
Other Name: Rituxan




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 [ Time Frame: Through study completion, an expected average of 6 months ]
    Safety and tolerability of NKTR-255 as evaluated by incidence of Dose Limiting Toxicities (DLTs), drug-related Adverse Events (AEs), Serious Adverse Events (SAEs), AEs leading to discontinuation, deaths, clinical laboratory abnormalities per CTCAE v5.

  2. Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 with Daratumumab [ Time Frame: Through study completion, an expected average of 1 year ]
    Safety and tolerability of NKTR-255 in combination with daratumumab as evaluated by incidence of drug-related AEs, SAEs, AEs leading to discontinuation, deaths, clinical laboratory abnormalities per CTCAE v5

  3. Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 with Rituximab [ Time Frame: Through study completion, an expected average of 1 year ]
    Safety and tolerability of NKTR-255 in combination with rituximab as evaluated by incidence of drug-related AEs, SAEs, AEs leading to discontinuation, deaths, clinical laboratory abnormalities per CTCAE v5



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Patients must have relapsed or refractory MM or NHL with no available therapies that would confer clinical benefit for their primary disease.
  • Measurable or detectable disease according to International Myeloma Working Group (IMWG) and the Lugano Classification. Extranodal NHL disease that is measurable by fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging only is allowed.
  • Estimated glomerular filtration rate (eGFR) ≥ 40 mL/min/1.73 m2.

Patient has the following laboratory test results during Screening:

  1. Absolute neutrophil count (ANC) or absolute granulocyte count (AGC) ≥ 1000/µL
  2. Platelets ≥ 30,000/µL
  3. Hemoglobin ≥ 8g/dL
  4. Absolute lymphocytes ≥ 800/µL
  5. Leukocytes ≥ 3000/µL

Patients are eligible who also meet all the following criteria in these cohorts of Part 2:

Cohort A only:

• Patients with NHL who received a commercially approved CD19 CAR-T product and had PD. The first dose of NKTR-255 will be administered within 30 days of the PD.

Cohort B only:

  • Patients with MM must have had previous exposure to proteasome inhibitor, immunomodulatory agent (IMiD), and anti-CD38 therapy.
  • Patients who previously received daratumumab or other anti-CD38 therapies must have at least 6 months washout.

Cohort C only:

• Patients with relapsed or refractory iNHL who previously progressed during or following 1 or more prior systemic rituximab-containing (or another treatment with an anti-CD20 antibody-containing) regimens for lymphoma.

Key Exclusion Criteria:

  • Patients who have an active, known, or suspected autoimmune disease.
  • Any treatment-related neurotoxicity or cytokine release syndrome (CRS) prior to enrollment into the study should return to baseline before NKTR-255 treatment.
  • Active central nervous system (CNS) involvement with NHL.
  • Patients who have been previously treated with prior interleukin-2 or interleukin-15.
  • Patients who received daratumumab or other anti-CD38 therapies previously must have 6 months washout.
  • Patients who have had < 28 days since the last anti-cancer treatment, chemotherapy, biological therapy, or < 14 days from approved tyrosine kinase inhibitor therapy (sunitinib, sorafenib, vemurafenib, dabrafenib, cobimetinib), or systemic or inhaled steroid therapy at doses greater than 10 mg of prednisone or equivalent before administration of the first dose of study drug(s).
  • Prolonged Fridericia's corrected QT interval (QTcF) > 450 ms for men and > 470 ms for women at Screening.
  • Contraindication to or unable to receive daratumumab (Cohort B only)

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): NCT04136756


Contacts
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Contact: Nektar Recruitment 855-482-8676 StudyInquiry@nektar.com
Contact: Rebecca Sutton 855-482-8676

Locations
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United States, Arizona
CTCA Phoenix Recruiting
Goodyear, Arizona, United States, 85338
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
University of California at San Francisco Recruiting
San Francisco, California, United States, 94143
United States, Florida
H Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
United States, Georgia
Winship Cancer Institute, Emory University Recruiting
Atlanta, Georgia, United States, 30322
United States, Illinois
Rush University Medical Center Not yet recruiting
Chicago, Illinois, United States, 60612
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
New York Medical College Recruiting
Valhalla, New York, United States, 10595
United States, North Carolina
Duke University Health System Recruiting
Durham, North Carolina, United States, 27705
United States, Texas
MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Nektar Therapeutics
Investigators
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Study Director: Mario Marcondes, MD, PhD Nektar Therapeutics
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Responsible Party: Nektar Therapeutics
ClinicalTrials.gov Identifier: NCT04136756    
Other Study ID Numbers: 18-255-02
First Posted: October 23, 2019    Key Record Dates
Last Update Posted: June 16, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nektar Therapeutics:
relapsed
refractory
NKTR-255
CAR-T
daratumumab
interleukin-15 (IL-15)
MM
NHL
indolent
rituximab
Additional relevant MeSH terms:
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Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Rituximab
Daratumumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents