Clinical trial NCT00079716: Study of SGN-40 in Patients With Refractory or Recurrent Multiple Myeloma
Official title: A Phase I, Multi-Dose Study of SGN-40 (Anti-huCD40 mAb) in Patients With Refractory or Recurrent Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Antigens, CD40
Antibody, Monoclonal
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immunoproliferative Disorders
Lymphoproliferative Disorders
Paraproteinemias
Vascular Diseases
Antibody-Dependent Cell Cytotoxicity
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
First posted: 2004-03-16
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and activity of SGN-40 in a weekly dosage schedule as a single agent.

Detailed description: This is an open-label, multi-dose, single-arm, phase I, dose-escalation study to define the toxicity profile, maximum tolerated dose (MTD), pharmacokinetics, and antitumor activity of SGN-40 in patients with refractory or recurrent multiple myeloma.

A minimum of three patients will be entered into each dose-level cohort. All patients will receive a dose-loading schedule during the first two weeks. The maximum weekly dose will be 16mg/kg.

Eligibility criteria: Inclusion Criteria:

1. Patients must have refractory or recurrent secretory multiple myeloma (MM).
2. Patients must have failed at least two different prior systemic therapies for MM.
3. Patients may have received a maximum of five cytotoxic regimens.
4. Patients who have received any of the following must complete within the specified time frame below:

   * Autologous stem cell transplant - 12 weeks prior to first dose
   * Nitrogen Mustard agents, Melphalan, BCNU, IVIG, or monoclonal antibody therapy - 6 weeks prior to first dose
   * Chemotherapy, Radiation, or other therapies for MM - 4 weeks prior to first dose
5. Patients who have not undergone autologous stem cell transplantation must be either ineligible for stem cell transplantation or, if eligible, must have refused treatment by autologous stem cell transplantation.
6. Patients must have an ECOG performance status of ≤ 2 and a life expectancy \> three months.
7. Patients must be available for periodic blood sampling, study-related assessments, and management of toxicity at the treating institution for the entire duration of the study.
8. Patients must be at least 18 years of age.
9. Females of childbearing potential must have a negative β-HCG pregnancy test result within three days of enrollment. All patients must plan to use an effective contraceptive method during the course of the study.
10. Patients must meet baseline lab data requirements.
11. Patients must give written informed consent.

Exclusion Criteria:

1. Patients with non-secretory MM or solitary plasmacytoma or plasma cell leukemia.
2. Patients with a history of allogeneic transplantation.
3. Patients receiving plasmapheresis within four weeks prior to enrollment.
4. Patients undergoing major surgery within four weeks prior to enrollment.
5. Patients with a known hypersensitivity to recombinant proteins or any excipient contained in the drug formulation.
6. Patients with a history of other malignancies during the past five years with the exception of adequately treated basal or squamous cell skin cancer or cervical carcinoma in situ.
7. Patients with any active viral, bacterial, or systemic fungal infection within four weeks of enrollment.
8. Patients with a history of significant chronic or recurrent infections requiring treatment.
9. Patients with a history of active thrombosis within three months of enrollment.
10. Patients with a history of pulmonary embolism.
11. Patients with a history of migraines or severe headaches requiring medical therapy within 12 months of enrollment.
12. Patients who are pregnant or breastfeeding.
13. Patients with uncontrolled hypercalcemia.
14. Patients with any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment.
15. Patients with dementia or altered mental status that would preclude understanding and rendering of informed consent.

Primary outcomes:
measure: Adverse events and lab abnormalities.
Secondary outcomes:
Other outcomes:
Locations:
city: West Hollywood
country: United States
facility: James R. Berenson M.D., Inc.
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Cornell University
state: New York
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
Study officials:
affiliation: Seagen Inc.
name: Nancy Whiting, PharmD
role: STUDY_DIRECTOR
References:
citation: Hayashi T, Treon SP, Hideshima T, Tai YT, Akiyama M, Richardson P, Chauhan D, Grewal IS, Anderson KC. Recombinant humanized anti-CD40 monoclonal antibody triggers autologous antibody-dependent cell-mediated cytotoxicity against multiple myeloma cells. Br J Haematol. 2003 May;121(4):592-6. doi: 10.1046/j.1365-2141.2003.04322.x.
citation: Hussein M, Berenson JR, Niesvizky R, Munshi N, Matous J, Sobecks R, Harrop K, Drachman JG, Whiting N. A phase I multidose study of dacetuzumab (SGN-40; humanized anti-CD40 monoclonal antibody) in patients with multiple myeloma. Haematologica. 2010 May;95(5):845-8. doi: 10.3324/haematol.2009.008003. Epub 2010 Feb 4.