Non-Hodgkin LymphomaPhase 1NCT01032681
EMD 521873 in Advanced Solid Tumors, MTD Finding
A Phase 1 study testing EMD 521873 in people with Non-Hodgkin Lymphoma, run by Merck KGaA, Darmstadt, Germany at 5 sites in 2 countries.
Trial summary
Primary trial objective in this three arm trial is to assess the safety and tolerability of EMD 521873, and to determine whether the maximum tolerated dose (MTD) is reached with EMD 521873 doses of up to 1.5 mg/kg given alone or in combination with fixed, low-dose cyclophosphamide (CPA) in patients with metastatic or… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin Lymphoma
- What is being tested?
- EMD 521873
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Dec 2006to Jan 2012
- Phase
- Phase 1
- 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
- Signed written informed consent
- Male or female, aged ≥ 18 years, inpatient for treatment phase of cycle 1 and 2, outpatient treatment possible for subsequent cycles
- Histologically or cytologically proven metastatic or locally advanced solid tumors (epithelial or mesenchymal cancers) or B-cell non-Hodgkin lymphoma for which no standard therapy exists or after failure of standard therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at study entry and an estimated life expectancy of at least 3 months
- Adequate hematological function defined by WBC count ≥ 3 x 109/L with absolute neutrophil count (ANC) ≥ 1.5 x 109/L and lymphocyte count ≥ 0.5 x 109/L; platelet count ≥100 x 109/L; hemoglobin ≥9 g/dL ( If the laboratory values for hemoglobin are outside the required entry level at Screening, a patient may receive a transfusion of RBC. A stable hemoglobin level of ≥9 mg/dL for at least 7 days must be achieved prior to receiving the first dose of study medication.)
- Adequate hepatic function defined by a total bilirubin level ≤ 1.5 times the upper limit of normal (ULN) and aspartate-aminotransferase (AST) and alanine-aminotransferase (ALT) levels ≤ 2.5 x ULN or, for patients with documented metastatic disease to the liver, AST and ALT levels ≤ 5 x ULN
- No history of acute or chronic kidney disease and adequate renal function defined by an estimated creatinine clearance above 50 mL/min determined by 24-hour urine sampling or by the Cockcroft-Gault formula
- Effective contraception for both male and female subjects if the risk of conception exists
Who cannot join
- Prior IL-2 therapy within the last 6 months
- Requirement for concurrent anticancer treatment (chemotherapy, radiotherapy, immune therapy, cytokine therapy except erythropoietin) or for concurrent systemic therapy with steroids or other immunosuppressive agents. Short-term administration of steroids (i.e. for allergic reactions) is allowed.
- Radiotherapy, chemotherapy, surgery (excluding prior diagnostic biopsy) or any investigational drug in the 30 days before the start of treatment in this study
- Acquired immune defects such as human immunodeficiency virus (HIV)
- Systemic autoimmune disease (e.g. lupus erythematodes, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma)
- Organ transplant recipients
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- History of or active inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis)
- Chronic viral infections (e.g. hepatitis B virus [HBV], hepatitis C virus [HCV])
- Uncontrolled hypertension (systolic >180 mmHg, diastolic >100 mmHg)
- Known hypersensitivity reactions to any of the compounds of the study medication
- Confirmed or clinically suspected brain metastases
- Pregnancy (absence to be confirmed by beta-human chorionic gonadotropin [β-HCG] test) or lactation period
- Clinically significant (i.e. active) cardiovascular disease: Cerebral vascular accident /stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina, congestive heart failure or serious cardiac arrhythmia requiring medication.
- Pulmonary disease which, in the opinion of the investigator, might impair the patient's respiratory tolerance to moderate pulmonary fluid overload (e.g. interstitial lung disease, severe chronic obstructive pulmonary disease)
- All conditions which are associated with significant necroses of non tumor-bearing tissues like e.g. esophageal or gastroduodenal ulcers (< 6 months prior to enrolment), organ infarctions (< 6 months prior to enrolment) or active ischemic bowel disease
- Presence of medically significant third space fluid (pericardial effusion or ascites/ pleural infusion requiring repetitive paracentesis)
- Known alcohol or drug abuse
- Participation in another clinical trial within the past 30 days before start of study treatment
- All other significant diseases which, in the opinion of the investigator, might impair the patient's tolerance of study treatment.
- Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Switzerland3 sites
Istituto Oncologico della Svizzera Italiana Ospedale Regionale Bellinzona e Valli (IOSI)
Bellinzona
University of Lausanne Hospitals (CHUV) and Hospitals of Riveria-Chablais
Lausanne
Kantonsspital St. Gallen
Sankt Gallen
Germany2 sites
Universitäts-Klinikum Mainz III.Medizinische Klinik
Mainz
Medizinische Klinik Universitätsklinikum Mannheim Medizinische Fakultät Mannheim
Mannheim
About this study
Official title: A Phase 1, Open-Label, Two-Group, Dose- Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of EMD 521873 Alone and in Combination With Fixed Low Doses of Cyclophosphamide in Patients With Metastatic or Locally Advanced Solid Tumors or B-Cell Non-Hodgkin Lymphoma
Primary trial objective in this three arm trial is to assess the safety and tolerability of EMD 521873, and to determine whether the maximum tolerated dose (MTD) is reached with EMD 521873 doses of up to 1.5 mg/kg given alone or in combination with fixed, low-dose cyclophosphamide (CPA) in patients with metastatic or locally advanced solid tumors or B-cell non-Hodgkin lymphoma.
Secondary objectives are to evaluate pharmacokinetic, immunogenicity, overall and best clinical response, changes in tumor marker levels, survival and biological/immune responses to EMD 521873. A total of 78 patients are planned. Patients will remain on the dose throughout the trial. It is intended to administer 3 cycles (21 d each, or until progression or a xxx line therapy becomes necessary.
- Conditions
- Non-Hodgkin Lymphoma
- Being tested
- EMD 521873
- Keywords
- Solid tumor, B-Cell Non-Hodgkin Lymphoma, Immunocytokine, interleukin-2, immunotherapy, Metastatic or Locally Advanced Solid Tumors or B-Cell Non-Hodgkin Lymphoma
- Medical subject headings
- Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EMD 521873Biological
Dose escalation steps:
Group 1: 0,075mg/kg - 0,15mg/kg - 0,225mg/kg - 0,3mg/kg - 0,45mg/kg - 0,6mg/kg - 0,9mg/kg (-1,8mg/kg - 2,1mg/kg - 2,5mg/kg - 3,0mg/kg)
Disease control and decision of continuation in patient who benefit from the treatment:
Every second cycle
EMD 521873Biological
Dose escalation steps:
Group 2: CPA plus 0,6mg/kg - 0,9mg/kg
Disease control and decision of continuation in patient who benefit from the treatment:
Every second cycle
EMD 521873Biological
Dose escalation steps:
Group 3: 0,9mg/kg - 1,2mg/kg - 1,5mg/kg (-1,8mg/kg - 2,1mg/kg - 2,5mg/kg - 3,0mg/kg)
Disease control and decision of continuation in patient who benefit from the treatment:
Every second cycle
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Dose escalation of EMD 521873 monotheraphy 3 doses per cycle Receives: Biological: EMD 521873 |
| Group 2 | Experimental | Low dose CPA + Dose escalation of EMD 521873 three doses per cycle Receives: Biological: EMD 521873 |
| Group 3 | Experimental | Dose escalation of EMD 521873 monotheraphy 1 dose per cycle Receives: Biological: EMD 521873 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the safety and tolerability of EMD 521873
Measured: First administration of any dose of EMD521873 until last administration plus 30 days.
To determine whether the MTD is reached with EMD 521873 doses of up to 1.5 mg/kg given alone or in combination with fixed, low-dose CPA in patients with metastatic or locally advanced solid tumors or B-cell non-Hodgkin lymphoma
Measured: Incidence of DLTs occurring during the first cycle of administration of any dose of EMD 521873 given alone on 3 times per cycle (group 1) or with fixed low-dose CPA plus EMD 521873 (group 2) or of EMD 521873 given alone on once per cycle (group 3).
Secondary outcomes (5)
Characterize the PK profile of EMD 521873 alone or in combination with fixed lowdose CPA
Measured: Cycle 1-3 of EMD 521873 treatment
Evaluate the immunogenicity of EMD 521873 alone or in combination with CPA measured by the induction of o Specific antibodies against the genetically modified IL-2 o Fc-IL2-specific antibodies o Anti-idiotype antibodies
Measured: Every EMD 521873 treatment cycle
Collect evidence of best overall response, changes in serum tumor marker levels and best clinical response after treatment with EMD 521873 alone or in combination with CPA
Measured: Every second EMD 521873 treatment cycle
Evaluate survival
Measured: Until 1 year after the last patient received his last dose of EMD 521873
Evaluate biological responses to EMD 521873 alone or in combination with CPA as measured by o Absolute cell numbers and ratios of lymphocyte subsets in defined combinations o Change in serum level of sIL2R and neopterin
Measured: Cycle 1-3 of EMD 521873 treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2009 (estimated)
- Study startDec 2006
- Primary completionFeb 2011
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Hodgkin LymphomaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jens-Peter Marschner, MD, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01032681
- Sponsor's protocol ID
- EMR62235_001
- Status last verified
- Oct 2012
- First submitted
- 11 Dec 2009
- Last updated
- 31 Jul 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Two-Group, Dose- Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of EMD 521873 Alone and in Combination With Fixed Low Doses of Cyclophosphamide in Patients With Metastatic or Locally Advanced Solid Tumors or B-Cell Non-Hodgkin Lymphoma
- ClinicalTrials.gov ID
- NCT01032681
- Acronym / sponsor ID
- EMR62235_001
- Conditions
- Non-Hodgkin Lymphoma
- Keywords
- Solid tumor, B-Cell Non-Hodgkin Lymphoma, Immunocytokine, interleukin-2, immunotherapy, Metastatic or Locally Advanced Solid Tumors or B-Cell Non-Hodgkin Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- Dec 2006
- Primary completion
- Feb 2011 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 15 Dec 2009 (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.
Primary trial objective in this three arm trial is to assess the safety and tolerability of EMD 521873, and to determine whether the maximum tolerated dose (MTD) is reached with EMD 521873 doses of up to 1.5 mg/kg given alone or in combination with fixed, low-dose cyclophosphamide (CPA) in patients with metastatic or locally advanced solid tumors or B-cell non-Hodgkin lymphoma.
Secondary objectives are to evaluate pharmacokinetic, immunogenicity, overall and best clinical response, changes in tumor marker levels, survival and biological/immune responses to EMD 521873. A total of 78 patients are planned. Patients will remain on the dose throughout the trial. It is intended to administer 3 cycles (21 d each, or until progression or a xxx line therapy becomes necessary.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Biological: EMD 521873Dose escalation of EMD 521873 monotheraphy 3 doses per cycle |
| Group 2 | Experimental | Biological: EMD 521873Low dose CPA + Dose escalation of EMD 521873 three doses per cycle |
| Group 3 | Experimental | Biological: EMD 521873Dose escalation of EMD 521873 monotheraphy 1 dose per cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Signed written informed consent
- Male or female, aged ≥ 18 years, inpatient for treatment phase of cycle 1 and 2, outpatient treatment possible for subsequent cycles
- Histologically or cytologically proven metastatic or locally advanced solid tumors (epithelial or mesenchymal cancers) or B-cell non-Hodgkin lymphoma for which no standard therapy exists or after failure of standard therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at study entry and an estimated life expectancy of at least 3 months
- Adequate hematological function defined by WBC count ≥ 3 x 109/L with absolute neutrophil count (ANC) ≥ 1.5 x 109/L and lymphocyte count ≥ 0.5 x 109/L; platelet count ≥100 x 109/L; hemoglobin ≥9 g/dL ( If the laboratory values for hemoglobin are outside the required entry level at Screening, a patient may receive a transfusion of RBC. A stable hemoglobin level of ≥9 mg/dL for at least 7 days must be achieved prior to receiving the first dose of study medication.)
Key exclusion criteria (20 listed)
- Prior IL-2 therapy within the last 6 months
- Requirement for concurrent anticancer treatment (chemotherapy, radiotherapy, immune therapy, cytokine therapy except erythropoietin) or for concurrent systemic therapy with steroids or other immunosuppressive agents. Short-term administration of steroids (i.e. for allergic reactions) is allowed.
- Radiotherapy, chemotherapy, surgery (excluding prior diagnostic biopsy) or any investigational drug in the 30 days before the start of treatment in this study
- Acquired immune defects such as human immunodeficiency virus (HIV)
- Systemic autoimmune disease (e.g. lupus erythematodes, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma)
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 |
|---|---|---|
| EMD 521873Dose escalation steps: Group 1: 0,075mg/kg - 0,15mg/kg - 0,225mg/kg - 0,3mg/kg - 0,45mg/kg - 0,6mg/kg - 0,9mg/kg (-1,8mg/kg - 2,1mg/kg - 2,5mg/kg - 3,0mg/kg) Disease control and decision of continuation in patient who benefit from the treatment: Every second cycle | Biological | Group 1 |
| EMD 521873Dose escalation steps: Group 2: CPA plus 0,6mg/kg - 0,9mg/kg Disease control and decision of continuation in patient who benefit from the treatment: Every second cycle | Biological | Group 2 |
| EMD 521873Dose escalation steps: Group 3: 0,9mg/kg - 1,2mg/kg - 1,5mg/kg (-1,8mg/kg - 2,1mg/kg - 2,5mg/kg - 3,0mg/kg) Disease control and decision of continuation in patient who benefit from the treatment: Every second cycle | Biological | Group 3 |
Primary outcome
Assess the safety and tolerability of EMD 521873
Time frame: First administration of any dose of EMD521873 until last administration plus 30 days.
To determine whether the MTD is reached with EMD 521873 doses of up to 1.5 mg/kg given alone or in combination with fixed, low-dose CPA in patients with metastatic or locally advanced solid tumors or B-cell non-Hodgkin lymphoma
Time frame: Incidence of DLTs occurring during the first cycle of administration of any dose of EMD 521873 given alone on 3 times per cycle (group 1) or with fixed low-dose CPA plus EMD 521873 (group 2) or of EMD 521873 given alone on once per cycle (group 3).
5 secondary outcomes
Characterize the PK profile of EMD 521873 alone or in combination with fixed lowdose CPA
Time frame: Cycle 1-3 of EMD 521873 treatment
Evaluate the immunogenicity of EMD 521873 alone or in combination with CPA measured by the induction of o Specific antibodies against the genetically modified IL-2 o Fc-IL2-specific antibodies o Anti-idiotype antibodies
Time frame: Every EMD 521873 treatment cycle
Collect evidence of best overall response, changes in serum tumor marker levels and best clinical response after treatment with EMD 521873 alone or in combination with CPA
Time frame: Every second EMD 521873 treatment cycle
Evaluate survival
Time frame: Until 1 year after the last patient received his last dose of EMD 521873
Evaluate biological responses to EMD 521873 alone or in combination with CPA as measured by o Absolute cell numbers and ratios of lymphocyte subsets in defined combinations o Change in serum level of sIL2R and neopterin
Time frame: Cycle 1-3 of EMD 521873 treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2014.
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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.
Jens-Peter Marschner, MD study director
Merck KGaA, Darmstadt, Germany
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EMD 521873 in people with Non-Hodgkin Lymphoma, run by Merck KGaA, Darmstadt, Germany at 5 sites in 2 countries.
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 8 inclusion and 20 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: finished, as of the sponsor's last update on 31 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Switzerland, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess the safety and tolerability of EMD 521873 (time frame: First administration of any dose of EMD521873 until last administration plus 30 days.). 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?
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 31 Jul 2014.