Safety and Pharmacokinetics of Rising Doses of APO010 in Relapsed/Refractory Multiple Myeloma Patients Selected by DRP

NCT03196947 | Terminated Phase 1 DMC

• 1 other identifier: APO010/P1/002
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Relapsed/Refractory Multiple Myeloma

Keywords

multiple myeloma; APO010; Drug Response Predictor; DRP

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dosage

  To define the Maximum Tolerated Dosage of intravenous bolus administration of APO010

  1 Year

• Recommended Dosage

  To define the Recommended Dosage of intravenous bolus administration of APO010

  1 Year

Secondary Outcomes (9)

• Percentage (%) of patients with drug-related adverse events (adverse reactions)

  1 Year

• The pharmacokinetic profile (AUC INF) for APO010 at doses above 60 µg/m2

  1 Year

• The pharmacokinetic profile (AUC last) for APO010 at doses above 60 µg/m2

  1 Year

• The pharmacokinetic profile (AUC 0-12hr) for APO010 at doses above 60 µg/m2

  1 Year

• The Maximum Plasma Concentration (Cmax), for APO010 at doses above 60 µg/m2

  1 Year

Study Arms (1)

Single arm, APO010 Dose escalation

EXPERIMENTAL

Drug: APO010

Interventions

APO010 DRUG

APO010 is given iv on D1, D8 and D15 followed by a one-week drug rest (cycle duration 4 weeks).

Single arm, APO010 Dose escalation

Eligibility Criteria

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

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Allarity Therapeutics: lead
• Smerud Medical Research International AS: collaborator
• Medical Prognosis Institute A/S: collaborator

Study Sites (1)

University Hospital of Copenhagen

Copenhagen, 2100, Denmark

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Mega-Fas-ligand

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Annette J Vangsted, DMSc

  Rigshospitalet, Finsen Centre, Hematological Department,, Phase 1 Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose Escalation followed by an extension phase using the recommended dosage

Study Record Dates

• First Submitted: May 19, 2017
• First Posted: June 23, 2017
• Study Start: June 13, 2017
• Primary Completion: January 16, 2020
• Study Completion: January 16, 2020
• Last Updated: January 30, 2020

Record last verified: 2020-01

Locations

DK (1)