Lymphoma, Large B-Cell, Diffuse (DLBCL)Phase 2NCT02544724
NM-IL-12 (rHuIL-12) In Relapsed/Refractory Diffuse Large B- Cell Lymphoma (DLBCL) Undergoing Salvage Chemotherapy
A Phase 2 study testing NM-IL-12 in people with Lymphoma, Large B-Cell, Diffuse (DLBCL), run by Neumedicines Inc..
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Large B-Cell, Diffuse (DLBCL)
- What is being tested?
- NM-IL-12
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- No sites listed yet
- Study dates
- Nov 2016to Dec 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 20Show fewer
- 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
- Prothrombin time (PT) and PTT 80% to 120% of institutional normal range
- Women of childbearing potential must have a negative serum pregnancy test and must agree to use effective contraception, defined as intrauterine devices, double barrier method (condom plus spermicide or diaphragm) or abstain from sexual intercourse during the study
- Male subjects must be willing to use an appropriate method of contraception (e.g., condoms) or abstain from sexual intercourse and inform any sexual partners that they must also use a reliable method of contraception (e.g., birth control pills) during the study
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures
- Ability to understand and willingness to sign a written informed consent document
Who cannot join
- 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
Show all 19Show fewer
- 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.
- Major bleeding within the last 6 months.
- Bleeding involving CNS within the last 12 months.
- Use of any investigational agents within 30 days prior to enrollment and for the duration of the study
- Pregnancy or lactation -
Trial locations and contacts
No sites are listed yet.
Shawn Jackson, M.Ed. contact
About this study
Official title: Single-Arm, Open-Label Study To Evaluate The Safety, Tolerability And Preliminary Efficacy Of NM-IL-12 (rHuIL-12) In Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Undergoing Salvage Chemotherapy
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.
Read the detailed description
This is a single-arm, open-label, non-randomized, multi-center study with NM-IL-12 dosed in combination with salvage chemotherapy regimens (R-ICE = rituximab plus ifosfamide-carboplatin-etoposide, R-DHAP = rituximab plus cytosine arabinoside-cisplatin-dexamethasone) for treatment of patients with relapsed/refractory DLBCL.
NM-IL-12 (150 ng/kg) will be administered subcutaneously. Patients will be monitored as routinely practiced; in addition, approximately 1 day after NM-IL-12 injection, patients will have a home visit by a nurse for blood sampling related to pharmacokinetic and pharmacodynamic (PK/PD) evaluation.
Twelve patients are planned to be enrolled into the study; initially 6 patients will be enrolled. The decision to continue and recruit the remaining six patients will be made by Data Safety Monitoring Board (DSMB) after review of relevant safety data, clinical laboratory evaluations, and vital signs collected up to 21 days post enrollment of the last patient in the first treated group. Common Terminology Grades for Adverse Events (CTCAE) guidelines will be used to determine dose-modifying criteria (DMC).
- Conditions
- Lymphoma, Large B-Cell, Diffuse (DLBCL)
- Being tested
- NM-IL-12
- Keywords
- Relapsed, Refractory, DLBCL, Chemotherapy
- Medical subject headings
- Lymphoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NM-IL-12Biological
Also called rHu-IL12
Single SC administration of NM-IL-12 will be administered at least 48 hours after completion of the last chemotherapy dose of each cycle
| Study group | Role | What they receive |
|---|---|---|
| NM-IL-12 | Experimental | NM-IL-12 will be administered subcutaneously Receives: Biological: NM-IL-12 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 months
Immunogenicity of NM-IL-12
Immunogenicity of NM-IL-12 will be evaluated by the presence of anti-drug antibody (ADA)
Measured: 4 months
Secondary outcomes (9)
Response rate (Complete Response or Partial Response) as assessed by PET/CT
Comparison will be made between the status before salvage regimen initiation, after the second chemotherapy cycle, and after completion of all salvage chemotherapy cycles. CR and PR will be assessed according to the revised International Working Group Criteria for non-Hodgkin Lymphoma.
Measured: 4 months
Time to neutrophil recovery
Time to neutrophil recovery, as defined by first day of ANC ≥ 500/μL
Measured: 4 months
Time to platelet count recovery
Time to platelet count recovery, as defined by first day of self-sustained platelet count ≥ 20,000/μL
Measured: 4 months
Incidence of systemic infections
Measured: 4 months
Incidence and duration of neutropenic fever
Measured: 4 months
Need for RBC and platelet transfusion
Measured: 4 months
Peak Plasma Concentration (Cmax) of NM-IL-12
Measured: 2 months
Area under the plasma concentration versus time curve (AUC) of NM-IL-12
Measured: 2 months
Peak Plasma Concentration (Cmax) of IFN-g and IP-10
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2015 (estimated)
- Study startNov 2016
- Primary completionAug 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Lymphoma, Large B-Cell, Diffuse (DLBCL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Neumedicines Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yossef Kalish, MD, Principal investigator, Hadassah Medical Organization
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02544724
- Sponsor's protocol ID
- NM-ONC-002
- Status last verified
- Aug 2016
- First submitted
- 4 Sep 2015
- Last updated
- 3 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24725395Gluzman-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.
PubMed 24852354Gluzman-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.
PubMed 24708888Basile 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.
PubMed 22383962
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-Arm, Open-Label Study To Evaluate The Safety, Tolerability And Preliminary Efficacy Of NM-IL-12 (rHuIL-12) In Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Undergoing Salvage Chemotherapy
- ClinicalTrials.gov ID
- NCT02544724
- Acronym / sponsor ID
- NM-ONC-002
- Conditions
- Lymphoma, Large B-Cell, Diffuse (DLBCL)
- Keywords
- Relapsed, Refractory, DLBCL, Chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Neumedicines Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2016
- Primary completion
- Aug 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 9 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a single-arm, open-label, non-randomized, multi-center study with NM-IL-12 dosed in combination with salvage chemotherapy regimens (R-ICE = rituximab plus ifosfamide-carboplatin-etoposide, R-DHAP = rituximab plus cytosine arabinoside-cisplatin-dexamethasone) for treatment of patients with relapsed/refractory DLBCL.
NM-IL-12 (150 ng/kg) will be administered subcutaneously. Patients will be monitored as routinely practiced; in addition, approximately 1 day after NM-IL-12 injection, patients will have a home visit by a nurse for blood sampling related to pharmacokinetic and pharmacodynamic (PK/PD) evaluation.
Twelve patients are planned to be enrolled into the study; initially 6 patients will be enrolled. The decision to continue and recruit the remaining six patients will be made by Data Safety Monitoring Board (DSMB) after review of relevant safety data, clinical laboratory evaluations, and vital signs collected up to 21 days post enrollment of the last patient in the first treated group. Common Terminology Grades for Adverse Events (CTCAE) guidelines will be used to determine dose-modifying criteria (DMC).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NM-IL-12 | Experimental | Biological: NM-IL-12NM-IL-12 will be administered subcutaneously |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NM-IL-12Also: rHu-IL12Single SC administration of NM-IL-12 will be administered at least 48 hours after completion of the last chemotherapy dose of each cycle | Biological | NM-IL-12 |
Primary outcome
Safety and tolerability
Time frame: 4 months
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.
Immunogenicity of NM-IL-12
Time frame: 4 months
Immunogenicity of NM-IL-12 will be evaluated by the presence of anti-drug antibody (ADA)
9 secondary outcomes
Response rate (Complete Response or Partial Response) as assessed by PET/CT
Time frame: 4 months
Time to neutrophil recovery
Time frame: 4 months
Time to platelet count recovery
Time frame: 4 months
Incidence of systemic infections
Time frame: 4 months
Incidence and duration of neutropenic fever
Time frame: 4 months
Need for RBC and platelet transfusion
Time frame: 4 months
Peak Plasma Concentration (Cmax) of NM-IL-12
Time frame: 2 months
Area under the plasma concentration versus time curve (AUC) of NM-IL-12
Time frame: 2 months
Peak Plasma Concentration (Cmax) of IFN-g and IP-10
Time frame: 2 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2016.
- Background: PubMed 24725395Gokhale 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.
- Background: PubMed 24852354Gluzman-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.
- Background: PubMed 24708888Gluzman-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.
- Background: PubMed 22383962Basile 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shawn Jackson, M.Ed. contact
Yossef Kalish, MD principal investigator
Hadassah Medical Organization
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NM-IL-12 in people with Lymphoma, Large B-Cell, Diffuse (DLBCL), run by Neumedicines Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lena A Basile, PhD, JD (626-844-3800, basile@neumedicines.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability (time frame: 4 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02544724, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2016.