Drug SafetyPhase 1NCT01727778
Safety and Preliminary Efficacy Study of the Antibody PAT-SM6 in Patients With Relapsed or Refractory Multiple Myeloma
A Phase 1 study testing Anti-GRP78 monoclonal IgM antibody PAT-SM6 in people with Drug Safety, run by Patrys Ltd. at 1 site in Germany.
Trial summary
Primary To evaluate the safety and tolerability of escalating doses of an intravenous (i.v.) infusion of PAT-SM6 in subjects with relapsed or refractory multiple myeloma. Secondary To evaluate the efficacy and pharmacodynamics by analysis of serum and urine M protein, serum free light chains (FLC) κFLC and λFLC, total… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Drug Safety
- What is being tested?
- Anti-GRP78 monoclonal IgM antibody PAT-SM6
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteGermany
- Study dates
- Oct 2012to Apr 2014
- 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
- Male or female subjects ≥ 18 years of age
- Relapsed or refractory multiple myeloma defined as: Failure of at least 2 previous therapies including an immunomodulatory agent (thalidomide or lenalidomide) and a proteasome inhibitor (unless the subjects were not eligible or refused to receive those treatments), and with progressive disease, defined by an increase of serological or urine myeloma parameters by 25% to the last value
- Presence of serum M-protein ≥ 1 g per 100 mL (≥ 10 g/L) and/or urine M-protein ≥ 200 mg per 24-hour period and/or serum FLCs ≥ 10 mg per 100 mL (≥ 100 mg/L) combined with an abnormal ratio of lambda and kappa chains
- Life expectancy of > 6 months
- Karnofsky performance status ≥ 60%, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Absolute neutrophil count (ANC) ≥ 1.0 (1,000/mm3) and platelets ≥ 30 × 109/L without previous transfusion within the last 2 weeks before first study drug administration
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- Creatinine clearance ≥ 30 mL/min (calculated using the Cockcroft-Gault equation)
- Total bilirubin ≤ 2 × upper normal limit (UNL)
- Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × UNL
- Haemoglobin ≥ 8 g/dL
- If a female of childbearing potential, confirmation of a negative pregnancy test before enrolment and use of double-barrier contraception, oral contraceptive plus barrier contraceptive, or confirmation of having undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation
- If a male, use of an effective barrier method of contraception during the study and for 3 months after the last dose if sexually active with a female of childbearing potential
- Ability to comply with all study-related procedures, medication use, and evaluations
- Ability to understand and give written informed consent, and comply with the protocol
Who cannot join
- Primary refractory multiple myeloma
- Previous treatment with cytotoxic chemotherapy or large-field radiotherapy or other myeloma-specific therapy within 28 days prior to the screening visit (radiation to a single site as concurrent therapy is allowed)
- Treatment with a systemic investigational agent within 28 days prior to the screening visit
- Hypercalcemia (> 2.7 mmol/L)
- Extramedullary plasmocytoma not originating from bone or plasma cell leukaemia
- Previous allogenic stem cell transplantation
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- Known or suspected hypersensitivity to the excipients contained in the study drug formulation
- Significant uncontrolled cardiovascular disease or cardiac insufficiency (New York Heart Association (NYHA) classes III-IV)
- Prior therapy with other monoclonal antibodies
- Clinical or laboratory evidence of active hepatitis B (positive HBsAg with negative HBsAb) or hepatitis C (positive hepatitis c virus antibody and detectable hepatitis C virus RNA with ALT above the normal range)
- Positive HIV test result (ELISA or Western blot)
- History of ischemic colitis, stroke or myocardial infarction within the last 6 months
- Presence of diarrhoea of grade 2 or higher
- Any active uncontrolled systemic infection
- Any antibiotic therapy due to infections 2 weeks prior to first study drug administration
- Regular dose of corticosteroids during the 2 weeks prior to study entry or anticipated need of corticosteroids exceeding prednisone 20 mg/day or equivalent, or any other immunosuppressive therapy within 2 weeks prior to study entry.
- Major surgery ≤ 4 weeks prior to first study drug administration or ongoing side effects of such surgery
- Systemic diseases (cardiovascular, renal, hepatic, etc) that would prevent study treatment
- Multiple myeloma with central nervous system involvement.
- Second active malignant disease, currently requiring treatment (with the exception of basal cell carcinoma of the skin or curative surgery treated tumours).
- Pregnancy or breastfeeding in women and women of childbearing potential not using an acceptable method of birth control
- others
Trial locations and contacts
1 site in 1 country.
Germany1 site
Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II
Würzburg, 97080
About this study
Official title: Open-label, Single-centre, Phase I, Multi-dose Escalating Study to Investigate the Safety and Preliminary Efficacy of an i.v. Infusion of the Anti-GRP78 Monoclonal IgM Antibody PAT-SM6 in Patients With Relapsed or Refractory Multiple Myeloma
Primary
- To evaluate the safety and tolerability of escalating doses of an intravenous (i.v.) infusion of PAT-SM6 in subjects with relapsed or refractory multiple myeloma.
Secondary
- To evaluate the efficacy and pharmacodynamics by analysis of serum and urine M protein, serum free light chains (FLC) κFLC and λFLC, total immunoglobulins, β2-microglobulin, C-reactive protein (CRP), exploratory biomarkers and anti-PAT-SM6 antibodies.
- To evaluate the duration of response and the progression free survival.
Read the detailed description
Open-label, single-centre, dose escalation phase I study designed to investigate the safety and tolerability of intravenous (i.v.) infusions of PAT-SM6 administered over 90 minutes.
A screening examination will be performed within 14 days prior to dosing. Eligible subjects will receive 4 doses of PAT-SM6 (cycle 1: Day 1 and Day 3, cycle 2: Day 8 and Day 10). Subjects will be hospitalised for at least 48 hours after each dose administration (i.e. from Day 1 to Day 5 in cycle 1 and from Day 8 to Day 12 in cycle 2). During hospitalisation subjects will be under constant surveillance. Subjects will return for ambulatory visits on Days 15, 22, 29 and 36 for safety, pharmacokinetic (PK) and pharmacodynamic (PD) assessments.
Serological staging will be performed at baseline, on Day 29 (+/- 2 days) and Day 36 (+/-2 days). Response will be assigned by the International Myeloma Working Group (IMWG) uniform response criteria for multiple myeloma. Complete response (CR) will be confirmed by bone marrow aspiration; CT scans or other radiograph are only intended when clinical symptoms are suspicious for progressing disease or otherwise clinically indicated.
If a subject shows an at least partial response (PR) on Day 29 or Day 36 (4 doses) the sponsor discusses with the Data Safety Monitoring Board (DSMB) to give an additional 2 doses (therefore the maximal number of doses for each subject is 6 doses) and a further staging will be performed 14 and 21 days after the last dose administration.
A completion visit will be performed 4 days after the last serological staging (e.g. after cycle 2 on Day 40).
Four dose groups (cohorts) are planned: 0.3 mg/kg followed by doses of 1 mg/kg, 3 mg/kg and 6 mg/kg. Subjects will be enrolled in a strict sequential order.
Individual safety results obtained until Day 5 will be evaluated by the investigator and the sponsor before the next subject of the same dose group will be treated. After completion of all 3 subjects of a dose group, safety results of all subjects obtained until Day 15 will be reviewed by the DSMB and a decision for dose escalation will be made. Interim doses can be administered if the increase is thought to be too high.
Subjects who show definite signs of progressive disease including hypercalcemia, new osteolytic lesions or new soft tissue plasmocytoma will be withdrawn from the study at any time.
In case dose limited toxicity (DLT) was seen in a subject, further dosing of subjects in the same dose group will be discussed with the DSMB, in case of a second DLT in the same dose group dose escalation will be stopped and the study will be continued at the next lower intermediate dose level or the previous tested dose will be regarded as the maximum tolerated dose (MTD). The MTD is defined as the dose level below the dose inducing a DLT in 2 subjects within one dose level.
- Conditions
- Drug Safety
- Being tested
- Anti-GRP78 monoclonal IgM antibody PAT-SM6
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-GRP78 monoclonal IgM antibody PAT-SM6Biological
| Study group | Role | What they receive |
|---|---|---|
| Antibody treatment | Experimental | Intravenous infusion of the anti-GRP78 monoclonal IgM antibody PAT-SM6 group 1: 0.3mg/kg Group 2: 1.0mg/kg Group 3: 3mg/kg Group 4: 6mg/kg Receives: Biological: Anti-GRP78 monoclonal IgM antibody PAT-SM6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall frequency of adverse events (AEs) (clinical symptoms, laboratory abnormalities, serious adverse events (SAEs) and treatment limiting adverse events)
Measured: 14 days
Secondary outcomes (1)
Serum concentrations of PAT-SM6
Measured: 11 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2012 (estimated)
- Study startOct 2012
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Drug SafetyStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Patrys Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Max Top, MD, Principal investigator, Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Zentrum für Innere Medizin,
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01727778
- Sponsor's protocol ID
- PATCT-SM6-02
- Other IDs
- 2012-001893-27
- Status last verified
- Oct 2015
- First submitted
- 12 Nov 2012
- Last updated
- 22 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rasche L, Duell J, Castro IC, Dubljevic V, Chatterjee M, Knop S, Hensel F, Rosenwald A, Einsele H, Topp MS, Brandlein S. GRP78-directed immunotherapy in relapsed or refractory multiple myeloma - results from a phase 1 trial with the monoclonal immunoglobulin M antibody PAT-SM6. Haematologica. 2015 Mar;100(3):377-84. doi: 10.3324/haematol.2014.117945. Epub 2015 Jan 30.
PubMed 25637055
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Single-centre, Phase I, Multi-dose Escalating Study to Investigate the Safety and Preliminary Efficacy of an i.v. Infusion of the Anti-GRP78 Monoclonal IgM Antibody PAT-SM6 in Patients With Relapsed or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01727778
- Acronym / sponsor ID
- PATCT-SM6-02
- Conditions
- Drug Safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Patrys Ltd.Industry (pharma, biotech, devices)
- Study start
- Oct 2012
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 16 Nov 2012 (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
- To evaluate the safety and tolerability of escalating doses of an intravenous (i.v.) infusion of PAT-SM6 in subjects with relapsed or refractory multiple myeloma.
Secondary
- To evaluate the efficacy and pharmacodynamics by analysis of serum and urine M protein, serum free light chains (FLC) κFLC and λFLC, total immunoglobulins, β2-microglobulin, C-reactive protein (CRP), exploratory biomarkers and anti-PAT-SM6 antibodies.
- To evaluate the duration of response and the progression free survival.
Detailed description
Open-label, single-centre, dose escalation phase I study designed to investigate the safety and tolerability of intravenous (i.v.) infusions of PAT-SM6 administered over 90 minutes.
A screening examination will be performed within 14 days prior to dosing. Eligible subjects will receive 4 doses of PAT-SM6 (cycle 1: Day 1 and Day 3, cycle 2: Day 8 and Day 10). Subjects will be hospitalised for at least 48 hours after each dose administration (i.e. from Day 1 to Day 5 in cycle 1 and from Day 8 to Day 12 in cycle 2). During hospitalisation subjects will be under constant surveillance. Subjects will return for ambulatory visits on Days 15, 22, 29 and 36 for safety, pharmacokinetic (PK) and pharmacodynamic (PD) assessments.
Serological staging will be performed at baseline, on Day 29 (+/- 2 days) and Day 36 (+/-2 days). Response will be assigned by the International Myeloma Working Group (IMWG) uniform response criteria for multiple myeloma. Complete response (CR) will be confirmed by bone marrow aspiration; CT scans or other radiograph are only intended when clinical symptoms are suspicious for progressing disease or otherwise clinically indicated.
If a subject shows an at least partial response (PR) on Day 29 or Day 36 (4 doses) the sponsor discusses with the Data Safety Monitoring Board (DSMB) to give an additional 2 doses (therefore the maximal number of doses for each subject is 6 doses) and a further staging will be performed 14 and 21 days after the last dose administration.
A completion visit will be performed 4 days after the last serological staging (e.g. after cycle 2 on Day 40).
Four dose groups (cohorts) are planned: 0.3 mg/kg followed by doses of 1 mg/kg, 3 mg/kg and 6 mg/kg. Subjects will be enrolled in a strict sequential order.
Individual safety results obtained until Day 5 will be evaluated by the investigator and the sponsor before the next subject of the same dose group will be treated. After completion of all 3 subjects of a dose group, safety results of all subjects obtained until Day 15 will be reviewed by the DSMB and a decision for dose escalation will be made. Interim doses can be administered if the increase is thought to be too high.
Subjects who show definite signs of progressive disease including hypercalcemia, new osteolytic lesions or new soft tissue plasmocytoma will be withdrawn from the study at any time.
In case dose limited toxicity (DLT) was seen in a subject, further dosing of subjects in the same dose group will be discussed with the DSMB, in case of a second DLT in the same dose group dose escalation will be stopped and the study will be continued at the next lower intermediate dose level or the previous tested dose will be regarded as the maximum tolerated dose (MTD). The MTD is defined as the dose level below the dose inducing a DLT in 2 subjects within one dose level.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Antibody treatment | Experimental | Biological: Anti-GRP78 monoclonal IgM antibody PAT-SM6Intravenous infusion of the anti-GRP78 monoclonal IgM antibody PAT-SM6 group 1: 0.3mg/kg Group 2: 1.0mg/kg Group 3: 3mg/kg Group 4: 6mg/kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Male or female subjects ≥ 18 years of age
- Relapsed or refractory multiple myeloma defined as: Failure of at least 2 previous therapies including an immunomodulatory agent (thalidomide or lenalidomide) and a proteasome inhibitor (unless the subjects were not eligible or refused to receive those treatments), and with progressive disease, defined by an increase of serological or urine myeloma parameters by 25% to the last value
- Presence of serum M-protein ≥ 1 g per 100 mL (≥ 10 g/L) and/or urine M-protein ≥ 200 mg per 24-hour period and/or serum FLCs ≥ 10 mg per 100 mL (≥ 100 mg/L) combined with an abnormal ratio of lambda and kappa chains
- Life expectancy of > 6 months
- Karnofsky performance status ≥ 60%, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Key exclusion criteria (22 listed)
- Primary refractory multiple myeloma
- Previous treatment with cytotoxic chemotherapy or large-field radiotherapy or other myeloma-specific therapy within 28 days prior to the screening visit (radiation to a single site as concurrent therapy is allowed)
- Treatment with a systemic investigational agent within 28 days prior to the screening visit
- Hypercalcemia (> 2.7 mmol/L)
- Extramedullary plasmocytoma not originating from bone or plasma cell leukaemia
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 |
|---|---|---|
| Anti-GRP78 monoclonal IgM antibody PAT-SM6 | Biological | Antibody treatment |
Primary outcome
Overall frequency of adverse events (AEs) (clinical symptoms, laboratory abnormalities, serious adverse events (SAEs) and treatment limiting adverse events)
Time frame: 14 days
1 secondary outcome
Serum concentrations of PAT-SM6
Time frame: 11 days
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 22 Oct 2015.
- Derived from this study: PubMed 25637055Rasche L, Duell J, Castro IC, Dubljevic V, Chatterjee M, Knop S, Hensel F, Rosenwald A, Einsele H, Topp MS, Brandlein S. GRP78-directed immunotherapy in relapsed or refractory multiple myeloma - results from a phase 1 trial with the monoclonal immunoglobulin M antibody PAT-SM6. Haematologica. 2015 Mar;100(3):377-84. doi: 10.3324/haematol.2014.117945. Epub 2015 Jan 30.
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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.
Max Top, MD principal investigator
Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Zentrum für Innere Medizin,
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Anti-GRP78 monoclonal IgM antibody PAT-SM6 in people with Drug Safety, run by Patrys Ltd. at 1 site in Germany.
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 14 inclusion and 22 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 22 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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?
Overall frequency of adverse events (AEs) (clinical symptoms, laboratory abnormalities, serious adverse events (SAEs) and treatment limiting adverse events) (time frame: 14 days). 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 NCT01727778, which also lists 1 linked publication.
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 22 Oct 2015.