NM-IL-12 (rHuIL-12) In Relapsed/Refractory Diffuse Large B- Cell Lymphoma (DLBCL) Undergoing Salvage Chemotherapy

NCT02544724 | Unknown Phase 2 DMC

• 1 other identifier: NM-ONC-002
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

NM-IL-12 is being evaluated as an immunotherapeutic with concomitant hematopoietic regenerating properties for treatment of relapsed/refractory DLBCL, an aggressive type of B-cell non-Hodgkin's lymphoma (NHL). Determination of the maximum tolerated dose (MTD) for NM-IL-12 is not planned in this study, rather, a pre-defined dose of 150 ng/kg will be explored; this dose is based on two safety and tolerability studies of NM-IL-12 in healthy volunteers.

Conditions

Lymphoma, Large B-Cell, Diffuse (DLBCL)

Keywords

Relapsed; Refractory; DLBCL; Chemotherapy

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability

  General safety: Vital signs (temperature, blood pressure, pulse rate, respiratory rate) and physical examination. • Toxicity according to the NCI CTCAE (v4.03) for AEs and clinical laboratory profile; AEs will be collected for all patients who received at least one dose of NM-IL-12 and up to one month post last NM-IL-12 dose.

  4 months

• Immunogenicity of NM-IL-12

  Immunogenicity of NM-IL-12 will be evaluated by the presence of anti-drug antibody (ADA)

  4 months

Secondary Outcomes (9)

• Response rate (Complete Response or Partial Response) as assessed by PET/CT

  4 months

• Time to neutrophil recovery

  4 months

• Time to platelet count recovery

  4 months

• Incidence of systemic infections

  4 months

• Incidence and duration of neutropenic fever

  4 months

Study Arms (1)

NM-IL-12

EXPERIMENTAL

NM-IL-12 will be administered subcutaneously

Biological: NM-IL-12

Interventions

NM-IL-12 BIOLOGICAL

Single SC administration of NM-IL-12 will be administered at least 48 hours after completion of the last chemotherapy dose of each cycle

Also known as: rHu-IL12

NM-IL-12

Eligibility Criteria

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

You may qualify if:

• Diagnosis of relapsed/refractory diffuse large B- cell lymphoma (DLBCL) within 28 days prior to enrollment
• PET/CT evaluation performed within 28 days prior to enrollment demonstrates measurable disease
• Age \>18 years
• Eligible for intensive salvage chemotherapy with R-ICE, R-DHAP
• Patient received first line of chemotherapy when DLBCL was initially diagnosed and did not receive any further chemotherapy until enrollment in this study
• All treatment-related toxicities from prior chemotherapy resolved to grade ≤ 1or resolved to grade 2 only if deemed clinically not significant and approved by the Sponsor
• ECOG performance status ≤ 2
• Adequate organ function obtained within 28 days prior to enrollment:
• Absolute neutrophil count ≥ 1,000/μL
• Platelet count ≥ 50,000/μL
• Total bilirubin ≤ 1.5x institutional upper limit of normal (IULN)
• AST and ALT ≤ 2x IULN
• Creatinine ≤ 2x IULN
• Creatinine clearance ≥ 45 mL/min/1.73m2 for participants with creatinine levels above IULN
• Albumin ≥ 2.5 g/dL

You may not qualify if:

• Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose of the first cycle of the chemotherapy regimen. Infections controlled on concurrent antimicrobial agents are acceptable, and antimicrobial prophylaxis per institutional guidelines are acceptable. Patient needs to be clinically stable as defined as being afebrile and hemodynamically stable for 24-48 hours prior to study enrollment
• Known active hepatitis B or C infections, known human immunodeficiency virus (HIV) infection or known to be positive for HCV RNA or HBsAg (HBV surface antigen)
• History of or active central nervous system (CNS) involvement by lymphoma
• Prior or concomitant malignancy in the past 5 years that is currently active and likely to interfere with the patient's treatment for DLBCL or that is likely to increase the patient's morbidity or mortality
• Concomitant illness associated with a likely survival of \< 1 year
• Any life-threatening illness, medical condition or organ system dysfunction that, in the investigator's opinion, could compromise the patient's safety, or put the study outcomes at undue risk
• Prior chemotherapy or radiation therapy (unless related to NHL / DLBCL treatment) within the last 5 years
• Cytotoxic drug therapy within 21 days prior to enrollment
• Unresolved toxicity from previous anticancer therapy (unless resolved to grade ≤ 1or resolved to grade 2 only if deemed clinically not significant and approved by the Sponsor) or incomplete recovery from surgery
• Major surgery (excluding that for diagnosis) within 28 days of enrollment
• Unstable cardiovascular function defined as:
• Symptomatic ischemia
• Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmic agents are excluded; first degree AV block or asymptomatic left anterior fascicular block \[LAFB\]/right bundle branch block \[RBBB\] will not be excluded), or
• Congestive heart failure NYHA Class ≥ 3, or myocardial infarction within 3 months prior to enrollment
• Cerebrovascular event (transient ischemic attack or stroke) within the last 12 months.

Sponsors & Collaborators

• Neumedicines Inc.: lead

Related Publications (4)

• Gokhale MS, Vainstein V, Tom J, Thomas S, Lawrence CE, Gluzman-Poltorak Z, Siebers N, Basile LA. Single low-dose rHuIL-12 safely triggers multilineage hematopoietic and immune-mediated effects. Exp Hematol Oncol. 2014 Apr 11;3(1):11. doi: 10.1186/2162-3619-3-11.

  PMID: 24725395 BACKGROUND

• Gluzman-Poltorak Z, Vainstein V, Basile LA. Recombinant interleukin-12, but not granulocyte-colony stimulating factor, improves survival in lethally irradiated nonhuman primates in the absence of supportive care: evidence for the development of a frontline radiation medical countermeasure. Am J Hematol. 2014 Sep;89(9):868-73. doi: 10.1002/ajh.23770. Epub 2014 Jun 19.

  PMID: 24852354 BACKGROUND

• Gluzman-Poltorak Z, Mendonca SR, Vainstein V, Kha H, Basile LA. Randomized comparison of single dose of recombinant human IL-12 versus placebo for restoration of hematopoiesis and improved survival in rhesus monkeys exposed to lethal radiation. J Hematol Oncol. 2014 Apr 6;7:31. doi: 10.1186/1756-8722-7-31.

  PMID: 24708888 BACKGROUND

• Basile LA, Ellefson D, Gluzman-Poltorak Z, Junes-Gill K, Mar V, Mendonca S, Miller JD, Tom J, Trinh A, Gallaher TK. HemaMax, a recombinant human interleukin-12, is a potent mitigator of acute radiation injury in mice and non-human primates. PLoS One. 2012;7(2):e30434. doi: 10.1371/journal.pone.0030434. Epub 2012 Feb 24.

  PMID: 22383962 BACKGROUND

MeSH Terms

Conditions

Lymphoma; Recurrence

Interventions

Interleukin-12 Subunit p35

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Interleukin-12; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Yossef Kalish, MD

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lena A Basile, PhD, JD

CONTACT

626-844-3800; basile@neumedicines.com

Shawn Jackson, M.Ed.

CONTACT

626-773-4920

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2015
• First Posted: September 9, 2015
• Study Start: November 1, 2016
• Primary Completion: August 1, 2017
• Study Completion: December 1, 2017
• Last Updated: August 3, 2016

Record last verified: 2016-08