A Phase I/IIa Study of Human Anti-CD38 Antibody MOR03087 (MOR202) in Relapsed/Refractory Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by MorphoSys AG
Sponsor:
Information provided by (Responsible Party):
MorphoSys AG
ClinicalTrials.gov Identifier:
NCT01421186
First received: July 29, 2011
Last updated: March 18, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: MOR03087 phase 1 dose escalation
Drug: MOR03087
Drug: Dexamethasone
Drug: Pomalidomide
Drug: Lenalidomide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/IIa, Open-Label, Multicentre, Dose-Escalation Study to Evaluate the Safety and Preliminary Efficacy of the Human Anti-CD38 Antibody MOR03087 as Monotherapy and in Combination With Standard Therapy in Subjects With Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by MorphoSys AG:

Primary Outcome Measures:
  • Determination of maximum tolerated dose and / or recommended dose and dosing regimen of MOR03087 [ Time Frame: First cycle of treatment ] [ Designated as safety issue: Yes ]
    1. As monotherapy
    2. In combination with dexamethasone
    3. In combination with pomalidomide + dexamethasone
    4. In combination with lenalidomide + dexamethasone

  • Safety will be evaluated by assessing adverse events, clinical laboratory data and vital signs [ Time Frame: until PD, maximum 2 years after 1st dose ] [ Designated as safety issue: Yes ]
  • Number of participants who develop anti-MOR03087 antibodies as a measure of immunogenicity [ Time Frame: until PD, maximum 2 years after 1st dose ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics of MOR03087 +/- lenalidomide or pomalidomide (pharmacokinetic assessment comprises: C max, t max, t 1/2, CL, AUC) [ Time Frame: until PD, maximum 2 years after 1st dose ] [ Designated as safety issue: No ]
  • Overall response rate, duration of response, time to progression (TTP) and progression-free survival (PFS) [ Time Frame: maximum 2 years after 1st dose ] [ Designated as safety issue: No ]

Estimated Enrollment: 126
Study Start Date: July 2011
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1 dose escalation

Part A: MOR03087 dose escalation; biweekly treatment

Part B: MOR03087 dose escalation; weekly treatment

Part C: MOR03087 dose escalation (weekly treatment) + dexamethasone

Part D: MOR03087 weekly treatment in combination with pomalidomide + dexamethasone

Part E: MOR03087 weekly treatment in combination with lenalidomide + dexamethasone

For all parts, patients will be treated until disease progression or until a maximum of 2 years after first treatment.

Drug: MOR03087 phase 1 dose escalation

Treatment cycles will be 28 days. Initial MOR03087 doses will be 0.01 mg/kg in part A, 4 mg/kg in parts B and C and 8 mg/kg in parts D and E; in all parts MOR03087 doses will be escalated to a maximum of 16 mg/kg. In part A, patients will receive a biweekly intravenous infusion of MOR03087 which will be administered on days 1 and 15 of the cycle. In parts B to E patients will receive a weekly intravenous infusion of MOR03087 which will be administered on days 1, 8, 15, and 22 of the cycle.

In all parts a loading dose of MOR03087 will be additionally administered on day 4 of cycle 1.

Drug: Dexamethasone
Dexamethasone will be administered to patients orally; 40 mg (≤ 75 years old) or 20 mg (> 75 years old) on days 1, 8, 15, and 22 of the 28-day cycle. An additional dose will be administered in cycle 1 on day 4.
Drug: Pomalidomide
Pomalidomide will be administered to patients orally 4 mg on days 1-21 of the 28-day cycle.
Drug: Lenalidomide
Lenalidomide will be administered to patients orally 25 mg on days 1-21 of the 28-day cycle.
Experimental: Phase 2a confirmatory cohorts

Confirmatory cohorts of MOR03087 monotherapy (plus or minus dexamethasone), in combination with pomalidomide plus dexamethasone, and in combination with lenalidomide plus dexamethasone.

Following completion of Parts A, B, and C (dose escalation of MOR03087 biweekly and weekly schedules), the MTD or recommended dose and dosing regimen will be confirmed in a minimum of 6 subjects.

Following completion of Parts D (dose escalation of MOR03087 in combination with pomalidomide + dexamethasone) and E (dose escalation of MOR03087 in combination with lenalidomide + dexamethasone), the MTD and/or recommended dose in each part will be confirmed in a minimum of 6 subjects.

For all parts, patients will be treated until disease progression or until a maximum of 2 years after first treatment.

Drug: MOR03087
MOR03087 will be administered according to the MTD or recommended dose and dosing regimen for MOR03087 from parts A-E of the phase I dose escalation. The biweekly MOR03087 regimen as described in part A; the weekly regimen as described for parts B-E.
Drug: Dexamethasone
Dexamethasone will be administered to patients orally; 40 mg (≤ 75 years old) or 20 mg (> 75 years old) on days 1, 8, 15, and 22 of the 28-day cycle. An additional dose will be administered in cycle 1 on day 4.
Drug: Pomalidomide
Pomalidomide will be administered to patients orally 4 mg on days 1-21 of the 28-day cycle.
Drug: Lenalidomide
Lenalidomide will be administered to patients orally 25 mg on days 1-21 of the 28-day cycle.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01421186

Contacts
Contact: Study Contact info@morphosys.com

Locations
Austria
AKH (Allgemeines Krankenhaus der Stadt Wien), Abteilung für Klinische Onkologie, Universitätsklinik für Innere Medizin I Recruiting
Vienna, Austria, 1090
Germany
Charité - Universitätsmedizin Berlin, CBF: Campus Benjamin Franklin, CC 14: Tumormedizin, Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie Recruiting
Berlin, Germany, 12200
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Recruiting
Dresden, Germany, 01307
Medizinische Klinik 5 - Hämatologie und Internist. Onkologie, Universitätsklinikum Erlangen Recruiting
Erlangen, Germany, 91054
Medizinische Universitätsklinik, Abt. Innere Medizin I Recruiting
Freiburg, Germany, 79106
Asklepios Klinik Altona, II. Medizinische Abteilung für Hämatologie/Onkologie Recruiting
Hamburg, Germany, 22763
Universitäsklinikum Heidelberg, Klin.-Pharmakologisches Studienzentrum Recruiting
Heidelberg, Germany, 69120
Sektion für Stammzell- und Immuntherapie, II. Medizinischen Klinik, Recruiting
Kiel, Germany, 24105
Klinikum rechts der Isar/ Studien / III. Med. Klinik Recruiting
Munich, Germany, 81675
Medizinische Klinik II, Abt. Hämatologie, Onkologie, Recruiting
Tübingen, Germany, 7206
Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Studienambulanz für Hämatologie/Onkologie und Infektiologie Recruiting
Würzburg, Germany, 97080
Sponsors and Collaborators
MorphoSys AG
  More Information

No publications provided

Responsible Party: MorphoSys AG
ClinicalTrials.gov Identifier: NCT01421186     History of Changes
Other Study ID Numbers: MOR202C101, DRKS00003145
Study First Received: July 29, 2011
Last Updated: March 18, 2015
Health Authority: Germany: Paul-Ehrlich-Institut
Austria: Federal Office for Safety in Health Care

Keywords provided by MorphoSys AG:
Multiple Myeloma
MOR03087 (MOR202)
Lenalidomide
Pomalidomide
CD38

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Pomalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents

ClinicalTrials.gov processed this record on September 03, 2015