Clinical trial NCT01421186: A Phase 1/2a Study of Human Anti-CD 38 Antibody MOR03087 (MOR202) in Relapsed/Refractory Multiple Myeloma
Official title: A Phase 1/2a, Open-Label, Multicentre, Dose-Escalation Study to Evaluate the Safety and Preliminary Efficacy of the Human Anti-CD 38 Antibody MOR03087 as Monotherapy and in Combination With Standard Therapy in Subjects With Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
MOR03087 (MOR202)
Lenalidomide
Pomalidomide
CD38
Lead sponsor: MorphoSys AG
Sponsor class: INDUSTRY
First posted: 2011-08-22
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, multicentre, dose escalation study to characterize the safety and preliminary efficacy of the human anti-CD38 antibody MOR03087 (MOR202), in adult subjects with relapsed/refractory multiple myeloma, as monotherapy and in adult subjects with relapsed/refractory multiple myeloma in combination with standard therapy.

Detailed description: The study enrolled patients aged 18 years or older with relapsed or refractory multiple myeloma and Karnofsky performance status of 60% or higher. Patients were assigned to the different treatment regimens with MOR202 ranging between 0·01 mg/kg and 16 mg/kg in a 3 + 3 design. Dose-escalation and expansion was done either with MOR202 intravenous infusions alone (MOR202 q2w \[twice a week\] and q1w \[weekly\] groups) or in combination with dexamethasone (MOR202 with dexamethasone group), with dexamethasone plus pomalidomide (MOR202 with dexamethasone plus pomalidomide group) or plus lenalidomide (MOR202 with dexamethasone plus lenalidomide group). Primary endpoints were safety, MOR202 maximum tolerated dose (or recommended dose) and regimen, and immunogenicity.

Eligibility criteria: Inclusion Criteria:

1. Male or female subjects 18 years and older
2. Relapsed or refractory multiple myeloma defined as:

   Parts A, B and C:

   (i) Failure of at least 2 previous therapies which must have included an immunomodulatory agent and a proteasome inhibitor (either together or part of different therapies) (ii) All subjects must have documented progression during or after their last prior therapy for multiple myeloma

   Part D:

   (i) At least 2 previous therapies including lenalidomide and a proteasome inhibitor (ii) All subjects must have documented progression during or within 60 days after their last prior therapy for multiple myeloma

   Part E:

   (i) Received at least one previous therapy (ii) All subjects must have documented progression during or after their last prior therapy for multiple myeloma
3. Presence of serum M-protein ≥ 0.5 g per 100 mL (≥ 5 g/L) and / or urine M-protein ≥ 200 mg per 24-hour period
4. Absolute neutrophil count (ANC) ≥ 1,000 / mm3
5. Haemoglobin ≥ 8 g/dL
6. Ability to comply with all study related procedures, medication use and evaluations

Exclusion Criteria:

1. Primary refractory multiple myeloma
2. History of significant cerebrovascular disease or sensory or motor neuropathy of toxicity grade 3 or higher
3. Treatment with systemic investigational agent within 28 days prior to first study treatment
4. Solitary plasmacytoma or plasma cell leukaemia
5. Previous allogenic stem cell transplant (SCT)
6. Prior therapy with other monoclonal antibodies targeting the CD38 antigen or prior therapy with other IgG monoclonal antibodies within 3 months prior to first study treatment, or IgM monoclonal antibodies within 1 month prior to first study treatment
7. Active systemic infection
8. Systemic disease preventing study treatment
9. Multiple myeloma with central nervous system (CNS) involvement
10. Previous treatment with cytotoxic chemotherapy or large field radiotherapy or other myeloma specific therapy within 28 days prior to first study treatment (radiation to a single site as concurrent therapy is allowed)
11. Significant uncontrolled cardiovascular disease or cardiac insufficiency (New York Heart Association \[NYHA\] classes III, IV)

Primary outcomes:
measure: Determination of Maximum Tolerated Dose and / or Recommended Dose and Dosing Regimen of MOR03087
timeFrame: First cycle of treatment
measure: Number of Participants Who Develop Anti-MOR03087 Antibodies
timeFrame: during treatment period, maximum 3 years after 1st dose
Secondary outcomes:
measure: Overall Response Rate
timeFrame: maximum 3 years after 1st dose
measure: Time to Progression
timeFrame: patients were observed for up to 36 months
measure: Progression-free Survival
timeFrame: patients were observed up to 36 months
measure: Duration of Response
timeFrame: patients were observed up to 36 months
measure: Pharmacokinetics: Cmax - Maximum Observed Serum Concentration for MOR202
timeFrame: up to 7 days after last MOR202 dose
measure: Pharmacokinetics: AUC Cycle 1+2 - Area Under the Time/Concentration Curve for MOR202
timeFrame: 56 days
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: AKH (Allgemeines Krankenhaus der Stadt Wien), Abteilung für Klinische Onkologie, Universitätsklinik für Innere Medizin I
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, CBF: Campus Benjamin Franklin, CC 14: Tumormedizin, Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie
city: Dresden
country: Germany
facility: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus
city: Erlangen
country: Germany
facility: Medizinische Klinik 5 - Hämatologie und Internist. Onkologie, Universitätsklinikum Erlangen
city: Freiburg
country: Germany
facility: Medizinische Universitätsklinik, Abt. Innere Medizin I
city: Heidelberg
country: Germany
facility: Universitäsklinikum Heidelberg, Klin.-Pharmakologisches Studienzentrum
city: Kiel
country: Germany
facility: Sektion für Stammzell- und Immuntherapie, II. Medizinischen Klinik,
city: Munich
country: Germany
facility: Klinikum rechts der Isar/ Studien / III. Med. Klinik
city: Tübingen
country: Germany
facility: Medizinische Klinik II, Abt. Hämatologie, Onkologie,
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Studienambulanz für Hämatologie/Onkologie und Infektiologie
Study officials:
References:
citation: Raab MS, Engelhardt M, Blank A, Goldschmidt H, Agis H, Blau IW, Einsele H, Ferstl B, Schub N, Rollig C, Weisel K, Winderlich M, Griese J, Hartle S, Weirather J, Jarutat T, Peschel C, Chatterjee M. MOR202, a novel anti-CD38 monoclonal antibody, in patients with relapsed or refractory multiple myeloma: a first-in-human, multicentre, phase 1-2a trial. Lancet Haematol. 2020 May;7(5):e381-e394. doi: 10.1016/S2352-3026(19)30249-2. Epub 2020 Mar 11.