Safety and Preliminary Efficacy Study of the Antibody PAT-SM6 in Patients With Relapsed or Refractory Multiple Myeloma

NCT01727778 | Completed Phase 1 DMC

• 2 other identifiers: PATCT-SM6-022012-001893-27
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Drug Safety

Outcome Measures

Primary Outcomes (1)

• Overall frequency of adverse events (AEs) (clinical symptoms, laboratory abnormalities, serious adverse events (SAEs) and treatment limiting adverse events)

  14 days

Secondary Outcomes (1)

• Serum concentrations of PAT-SM6

  11 days

Other Outcomes (2)

• Pharmacodynamics

  40 days

• Efficacy

  40 days

Study Arms (1)

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

Biological: Anti-GRP78 monoclonal IgM antibody PAT-SM6

Interventions

Anti-GRP78 monoclonal IgM antibody PAT-SM6 BIOLOGICAL

Antibody treatment

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Patrys Ltd.: lead

Study Sites (1)

Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II

Würzburg, 97080, Germany

Location

Related Publications (1)

• 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.

  PMID: 25637055 DERIVED

Study Officials

• Max Top, MD

  Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Zentrum für Innere Medizin,

  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

Study Record Dates

• First Submitted: November 12, 2012
• First Posted: November 16, 2012
• Study Start: October 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: October 22, 2015

Record last verified: 2015-10

Locations

DE (1)