Relapsed/Refractory Multiple MyelomaPhase 1/2SMR-3184NCT03196947
Safety and Pharmacokinetics of Rising Doses of APO010 in Relapsed/Refractory Multiple Myeloma Patients Selected by DRP
A Phase 1/2 study testing APO010 in people with Relapsed/Refractory Multiple Myeloma, run by Allarity Therapeutics at 1 site in Denmark.
Trial summary
Multicentre, open label, uncontrolled, phase I pharmacokinetic study, to determine the Maximum Tolerated Dose (MTD) of APO010 administered intravenously on D1, D8 and D15 followed by a one-week drug rest, in patients with multiple myeloma for who have relapsed or are refractory to 2 (in high-risk patients 1) or more… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed/Refractory Multiple Myeloma
- What is being tested?
- APO010
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteDenmark
- Study dates
- 13 Jun 2017to 16 Jan 2020
- Phase
- Phase 1/2
- 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
- Relapsed or relapsed/refractory to 2 (in high-risk patients 1) or more different prior therapies, including IMiDs and PI
- Measurable disease
- Serum M-protein > 10 g/l, or
- Urine M-protein > 200 mg/24 hours, or
- Serum involved-FLC (iFLC) > 100 mg/l and abnormal FLC ratio
- Have participated in the APO010 screening protocol in which Drug Response Predictor (DRP) outcome is measured as being in the upper likelihood of response (50% in dose-finding part and 25% in the expansion cohort)
Show all 18Show fewer
- Age > 18 years
- Adequate organ and bone marrow function as defined below:
- Absolute neutrophil count > 1.5 x 109/l (> 0.75 x 109/l in case > 50% plasma cell count in bone marrow)
- Platelet count > 50 x 109/l (> 30 x 109/l in case > 50% plasma cell count in bone marrow)
- Haemoglobin > 4.6 mmol/l (> 7.5 g/l)
- Bilirubin ≤ upper limit of normal
- aspartate aminotransferase (SGOT)/alanine transaminase (SGPT) ≤ upper limit of normal
- Creatinine < 1.5 x upper limit of normal or creatinine clearance > 50 ml/min calculated according to Cockcroft-Gault
- Eastern Cooperative Oncology Group (ECOG) performance status < 2
- Life expectancy of at least 3 months.
- Capability of understanding the nature of the study and giving written informed consent
- Signed informed consent form
Who cannot join
- Have central nervous system (CNS) myeloma
- Have plasma cell leukaemia defined as plasma cell count > 2000 / µL in peripheral blood
- Have symptomatic amyloidosis
- Have anti-myeloma treatment or radiotherapy within 3 weeks from first infusion
- Have received a cumulative dose of corticosteroid > 200 mg (dexamethasone, or equivalent dose of prednisone) within 2 weeks of the first infusion
- Have received any experimental drug or experimental therapy within 3 weeks before the first infusion
Show all 28Show fewer
- Have received autologous-stem cell transplantation (SCT) within 12 weeks before the first infusion
- Have received an allogeneic stem cell transplantation (SCT)
- Have had past or current malignancy except for:
- Cervical carcinoma < Stage 1B
- Non-invasive basal cell or squamous cell skin carcinoma
- Malignant melanoma with CR of > 10 years
- Any other curable cancer with a CR > 5 years
- Have major surgery within 4 weeks prior to the first infusion
- Have severe infection requiring iv treatment
- Have known HIV positivity
- Have known active hepatitis B or C
- Have had clinical significant arteriosclerotic events:
- Ischemic heart disease
- Unstable angina
- Myocardial infarction
- Transient ischemic attack
- Ischemic stroke
- Documented peripheral arteriosclerosis
- Have baseline QT interval as corrected by Fridericia's formula (QTcF) > 470 msec for female patients or > 450 msec for male patients or a complete left bundle branch block (defined as QRS interval > 120 msec in left bundle branch block form)
- CNS disease including epilepsy or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
- Women of childbearing age and potential who are not willing to use effective contraception during the study and at least until 90 days after last dose of study drug. Male patients or male patients who have female partners of childbearing age and potential who are not willing to use effective contraception during the study and at least until 90 days after last dose of study drug. Highly effective methods of birth control are defined as those which result in a low failure rate, i.e., less than 1% per year, when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intra-uterine devices, sexual abstinence or vasectomized partner
- Pregnant or breast-feeding women
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I, Open Label, Dose Escalation Study to Investigate the Tolerability and Efficacy of APO010 in Patients With Relapsed/Refractory Multiple Myeloma Selected by Drug Response Predictor (DRP)
Multicentre, open label, uncontrolled, phase I pharmacokinetic study, to determine the Maximum Tolerated Dose (MTD) of APO010 administered intravenously on D1, D8 and D15 followed by a one-week drug rest, in patients with multiple myeloma for who have relapsed or are refractory to 2 (in high-risk patients 1) or more different prior therapies and who have Drug Response Predictor (DRP) for APO010 indicating a higher likelihood for response to APO010. The study will contain an extension phase where the recommended Dose will be tested on additional patients.
Read the detailed description
APO010 is a novel investigational antitumour agent. It is a recombinant form of human Fas ligand (FasL), a protein with the function of inducing programmed cell death (apoptosis). Preclinical studies indicate that multiple myeloma is sensitive for APO010. Estimation of DRP for APO010 in myeloma patients suggests that it may be possible to identify patients with high and low likelihood for response, and thereby allocate the predicted high likelihood patients to the treatment. Preclinical results indicate that, in comparison with other single agents, APO010 exercises superior anti-tumour effect by inducing apoptosis.
The study will include patients with multiple myeloma who have relapsed or are refractory to 2 (in high-risk patients 1) or more different prior therapies, including IMiDs and PI and who have Drug Response Predictor (DRP) for APO010 indicating a higher likelihood for response to APO010.
This study is a multicentre, open label, uncontrolled, phase I, dose escalation, pharmacokinetic study, to determine the Maximum Tolerated Dose (MTD) of APO010 administered intravenously on D1, D8 and D15 followed by a one-week drug rest i.e. cycle duration is 4 weeks. The study will contain an extension phase where the Recommended Dose will be tested on additional patients.
The primary endpoint is determination of the Maximum Tolerated Dose (MTD)based upon first cycle drug-related dose-limiting toxicity and the recommended dose of APO010. Safety will be evaluated during the study and for 30 days after the last administration of study drug. Adverse events and laboratory studies will be graded according to NCI-CTCAE v. 4.03.
The proportion of patients with positive HADA assessment will be investigated and a description of any objective tumour response based on International Myeloma Working Group criteria and from changes in M-protein and iFLC.
- Conditions
- Relapsed/Refractory Multiple Myeloma
- Being tested
- APO010
- Keywords
- multiple myeloma, APO010, Drug Response Predictor, DRP
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APO010Drug
APO010 is given iv on D1, D8 and D15 followed by a one-week drug rest (cycle duration 4 weeks).
| Study group | Role | What they receive |
|---|---|---|
| Single arm, APO010 Dose escalation | Experimental | Not described Receives: Drug: APO010 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dosage
To define the Maximum Tolerated Dosage of intravenous bolus administration of APO010
Measured: 1 Year
Recommended Dosage
To define the Recommended Dosage of intravenous bolus administration of APO010
Measured: 1 Year
Secondary outcomes (9)
Percentage (%) of patients with drug-related adverse events (adverse reactions)
To define the safety profile of a weekly schedule of APO010, including Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.03, Physical examination, vital signs, concomitant medications and laboratory data. To define the safety profile of APO010 after chronic administration (beyond 3 consecutive administrations, i.e., two or more cycles) and to define local toxicity at the site of administration through observation of the area of infusion.
Measured: 1 Year
The pharmacokinetic profile (AUC INF) for APO010 at doses above 60 µg/m2
The PK variable that will be evaluated are Area Under the curve (AUC INF). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2
Measured: 1 Year
The pharmacokinetic profile (AUC last) for APO010 at doses above 60 µg/m2
The PK variable that will be evaluated are Area Under the curve (AUC last). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2
Measured: 1 Year
The pharmacokinetic profile (AUC 0-12hr) for APO010 at doses above 60 µg/m2
The PK variable that will be evaluated are Area Under the curve (AUC 0-12hr). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2
Measured: 1 Year
The Maximum Plasma Concentration (Cmax), for APO010 at doses above 60 µg/m2
The PK variable that will be evaluated is Maximum Plasma Concentration (Cmax). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2
Measured: 1 Year
The Observed maximum (Tmax), for APO010 at doses above 60 µg/m2
The PK variable that will be evaluated is, time of observed maximum (Tmax). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2
Measured: 1 Year
The Terminal half-life (T½), for APO010 at doses above 60 µg/m2
Pharmacokinetic (PK) parameters will be calculated or estimated by using a model independent approach. The PK variable that will be evaluated is the terminal half-life (T½)). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2
Measured: 1 Year
The HADA Antibody Response
Assays will be performed to detect the production of antibodies against APO010 (HADA) in the serum of treated patients. If antibodies are formed, their ability to neutralize the biological activity of APO010 in in vitro cytotoxicity assay will be measured.
Measured: 1 Year
The Tumor Response
Using International Myeloma Working Group (IMWG) response criteria, based on measurements in blood and urine and in case of disappearance of M-proteins with additional confirmatory bone-marrow investigation, the number of patients with either stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD) or progressive disease (PD) will be measured.
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2017
- Study start13 Jun 2017
- Primary completion16 Jan 2020
- Study completion16 Jan 2020
Why it stopped: The study was terminated early due to sponsors decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory Multiple MyelomaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Dose Escalation followed by an extension phase using the recommended dosage
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Allarity Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Smerud Medical Research International AS, Medical Prognosis Institute A/S
- Responsible party
- Sponsor
- Investigators
- Annette J Vangsted, DMSc, Principal investigator, Rigshospitalet, Finsen Centre, Hematological Department,, Phase 1 Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03196947
- Sponsor's protocol ID
- APO010/P1/002
- Acronym
- SMR-3184
- Status last verified
- Jan 2020
- First submitted
- 19 May 2017
- Last updated
- 30 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Open Label, Dose Escalation Study to Investigate the Tolerability and Efficacy of APO010 in Patients With Relapsed/Refractory Multiple Myeloma Selected by Drug Response Predictor (DRP)
- ClinicalTrials.gov ID
- NCT03196947
- Acronym / sponsor ID
- SMR-3184 / APO010/P1/002
- Conditions
- Relapsed/Refractory Multiple Myeloma
- Keywords
- multiple myeloma, APO010, Drug Response Predictor, DRP
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early due to sponsors decision
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Allarity TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Smerud Medical Research International AS, Medical Prognosis Institute A/S
- Study start
- 13 Jun 2017 (actual)
- Primary completion
- 16 Jan 2020 (actual)
- Study completion
- 16 Jan 2020 (actual)
- First posted
- 23 Jun 2017 (actual)
- 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.
Multicentre, open label, uncontrolled, phase I pharmacokinetic study, to determine the Maximum Tolerated Dose (MTD) of APO010 administered intravenously on D1, D8 and D15 followed by a one-week drug rest, in patients with multiple myeloma for who have relapsed or are refractory to 2 (in high-risk patients 1) or more different prior therapies and who have Drug Response Predictor (DRP) for APO010 indicating a higher likelihood for response to APO010. The study will contain an extension phase where the recommended Dose will be tested on additional patients.
Detailed description
APO010 is a novel investigational antitumour agent. It is a recombinant form of human Fas ligand (FasL), a protein with the function of inducing programmed cell death (apoptosis). Preclinical studies indicate that multiple myeloma is sensitive for APO010. Estimation of DRP for APO010 in myeloma patients suggests that it may be possible to identify patients with high and low likelihood for response, and thereby allocate the predicted high likelihood patients to the treatment. Preclinical results indicate that, in comparison with other single agents, APO010 exercises superior anti-tumour effect by inducing apoptosis.
The study will include patients with multiple myeloma who have relapsed or are refractory to 2 (in high-risk patients 1) or more different prior therapies, including IMiDs and PI and who have Drug Response Predictor (DRP) for APO010 indicating a higher likelihood for response to APO010.
This study is a multicentre, open label, uncontrolled, phase I, dose escalation, pharmacokinetic study, to determine the Maximum Tolerated Dose (MTD) of APO010 administered intravenously on D1, D8 and D15 followed by a one-week drug rest i.e. cycle duration is 4 weeks. The study will contain an extension phase where the Recommended Dose will be tested on additional patients.
The primary endpoint is determination of the Maximum Tolerated Dose (MTD)based upon first cycle drug-related dose-limiting toxicity and the recommended dose of APO010. Safety will be evaluated during the study and for 30 days after the last administration of study drug. Adverse events and laboratory studies will be graded according to NCI-CTCAE v. 4.03.
The proportion of patients with positive HADA assessment will be investigated and a description of any objective tumour response based on International Myeloma Working Group criteria and from changes in M-protein and iFLC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Dose Escalation followed by an extension phase using the recommended dosage
| Arm | Type | Receives |
|---|---|---|
| Single arm, APO010 Dose escalation | Experimental | Drug: APO010 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Relapsed or relapsed/refractory to 2 (in high-risk patients 1) or more different prior therapies, including IMiDs and PI
- Measurable disease
- Serum M-protein > 10 g/l, or
- Urine M-protein > 200 mg/24 hours, or
- Serum involved-FLC (iFLC) > 100 mg/l and abnormal FLC ratio
Key exclusion criteria (28 listed)
- Have central nervous system (CNS) myeloma
- Have plasma cell leukaemia defined as plasma cell count > 2000 / µL in peripheral blood
- Have symptomatic amyloidosis
- Have anti-myeloma treatment or radiotherapy within 3 weeks from first infusion
- Have received a cumulative dose of corticosteroid > 200 mg (dexamethasone, or equivalent dose of prednisone) within 2 weeks of the first infusion
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 |
|---|---|---|
| APO010APO010 is given iv on D1, D8 and D15 followed by a one-week drug rest (cycle duration 4 weeks). | Drug | Single arm, APO010 Dose escalation |
Primary outcome
Maximum Tolerated Dosage
Time frame: 1 Year
To define the Maximum Tolerated Dosage of intravenous bolus administration of APO010
Recommended Dosage
Time frame: 1 Year
To define the Recommended Dosage of intravenous bolus administration of APO010
9 secondary outcomes
Percentage (%) of patients with drug-related adverse events (adverse reactions)
Time frame: 1 Year
The pharmacokinetic profile (AUC INF) for APO010 at doses above 60 µg/m2
Time frame: 1 Year
The pharmacokinetic profile (AUC last) for APO010 at doses above 60 µg/m2
Time frame: 1 Year
The pharmacokinetic profile (AUC 0-12hr) for APO010 at doses above 60 µg/m2
Time frame: 1 Year
The Maximum Plasma Concentration (Cmax), for APO010 at doses above 60 µg/m2
Time frame: 1 Year
The Observed maximum (Tmax), for APO010 at doses above 60 µg/m2
Time frame: 1 Year
The Terminal half-life (T½), for APO010 at doses above 60 µg/m2
Time frame: 1 Year
The HADA Antibody Response
Time frame: 1 Year
The Tumor Response
Time frame: 1 Year
Results and safety
The study was stopped early (reason given: The study was terminated early due to sponsors decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2020.
Related trials for Relapsed/Refractory Multiple Myeloma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 3
A Trial to Learn How Well Linvoseltamab Works Compared to the Combination of Elotuzumab, Pomalidomide and Dexamethasone for Adult Participants With Relapsed/Refractory Multiple Myeloma
Relapsed Refractory Multiple Myeloma (RRMM)
RecruitingPhase 1/2
A Trial to Study if REGN17372 in Combination With Linvoseltamab is Tolerable for Adult Participants With Relapsed/Refractory Multiple Myeloma
Relapsed Refractory Multiple Myeloma (RRMM)
RecruitingPhase 1
A Study to Examine the Effects of Novel Therapy Linvoseltamab in Combination With Other Cancer Treatments for Adult Participants With Multiple Myeloma That is Resistant to Current Standard of Care Treatments
Multiple Myeloma
RecruitingPhase 1
A Study Evaluating the Safety, Pharmacokinetics, and Activity of the Combination of Cevostamab and Elranatamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)
Relapsed or Refractory Multiple Myeloma
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.
Annette J Vangsted, DMSc principal investigator
Rigshospitalet, Finsen Centre, Hematological Department,, Phase 1 Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing APO010 in people with Relapsed/Refractory Multiple Myeloma, run by Allarity Therapeutics at 1 site in Denmark.
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 18 inclusion and 28 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: stopped early, as of the sponsor's last update on 30 Jan 2020. 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 Denmark. 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 combined 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.
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?
The study was stopped early (reason given: The study was terminated early due to sponsors decision). Results are not available in the source record.
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?
Maximum Tolerated Dosage (time frame: 1 Year). 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 30 Jan 2020.