BB-10901 in Treating Patients With Relapsed and/or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as BB-10901, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. PURPOSE: This phase I trial is studying the side effects and best dose of BB-10901 in treating patients with relapsed and/or refractory multiple myeloma.

Detailed Description
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OBJECTIVES: Primary Determine the dose-limiting toxicity and the maximum tolerated dose of BB-10901 in patients with relapsed and/or refractory CD56-positive multiple myeloma. Secondary To determine the qualitative and quantitative toxicities of BB-10901 administered on this schedule. To evaluate the pharmacokinetics of BB-10901. To recommend a dose for Phase II clinical studies with BB-10901 given on this specific regimen. To observe any evidence of anti-tumor activity with BB-10901. Objectives of MTD Expansion Cohort To evaluate response rate including overall response rate (ORR) and complete response rate (CRR), and duration of response (DOR). To further assess time to progression (TTP), progression free survival (PFS), and overall survival (OS). OUTLINE: This is an open-label, non-randomized, dose-escalation, multicenter study. Patients receive BB-10901 IV over 1-2 hours on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of BB-10901 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Up to 40 patients are treated at the MTD. After completion of study treatment, patients are followed for short term follow-up and long term (up to 3 years) survival status. PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

Official Title
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A Phase I Study to Assess The Safety and Pharmacokinetics of BB-10901 (huN901-DM1) Given as an Intravenous Infusion Weekly for Two Consecutive Weeks Every Three Weeks to Subjects With Relapsed and Relapsed Refractory CD56-Positive Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: BB-10901


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed multiple myeloma Relapsed or relapsed/refractory disease Failed ≥ 1 prior therapy for multiple myeloma Once the MTD is defined, only patients who have received at least 1 but equal or less than 6 prior chemotherapy regimens will be enrolled at this dose level CD56-positive disease confirmed by immunohistochemistry or flow cytometry PATIENT CHARACTERISTICS: ECOG (Zubrod) performance status 0-2 Life expectancy ≥ 12 weeks Platelet count ≥ 75,000/mm^3 Absolute neutrophil count > 1,000/mm^3 Hemoglobin ≥ 8.5 g/dL AST and ALT ≤ 3 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN Amylase and lipase within normal limits Creatinine ≤ 2 mg/dL Left ventricular ejection fraction ≥ lower limit of normal on MUGA or ECHO Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No peripheral neuropathy ≥ grade 3 or painful grade 2 neuropathy No significant cardiac disease, including any of the following: Myocardial infarction within the past 6 months Unstable angina Uncontrolled congestive heart failure Uncontrolled hypertension (i.e., recurrent or persistent increases in systolic blood pressure ≥ 180 mm Hg or diastolic blood pressure ≥ 110 mm Hg) Uncontrolled cardiac arrhythmias Cardiac toxicity ≥ grade 3 after prior chemotherapy No history of multiple sclerosis or other demyelinating disease No hemorrhagic or ischemic stroke within the past 6 months No Eaton-Lambert syndrome (para-neoplastic syndrome) No CNS injury with residual neurological deficit (other than peripheral neuropathy ≤ grade 2) No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, or in situ prostate cancer No clinically relevant active infection, including active hepatitis B or C infection or HIV infection No other condition or disease, including laboratory abnormalities, that, in the opinion of the investigator, may preclude study treatment No known recent biochemical or clinical evidence of pancreatitis or extensive metastatic disease involving the pancreas PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) At least 4 weeks since prior radiotherapy At least 4 weeks since prior major surgery (except placement of a vascular access device or tumor biopsies) More than 4 weeks since prior investigational agents At least 2 weeks since prior antineoplastic therapy with biological agents No prior hypersensitivity to monoclonal antibody therapy No other concurrent investigational agents No concurrent corticosteroids (except as indicated for other medical conditions [< 10 mg prednisone or equivalent]; as pre-medication for administration of certain medications or blood products [≤ 100 mg hydrocortisone]; or for treatment of infusion reactions) Concurrent topical steroids allowed No other concurrent antineoplastic treatment (e.g., chemotherapy, radiotherapy, or biological agents) Concurrent bisphosphonates allowed provided patient began bisphosphonates before study entry and is maintained on a stable dose during study treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: BB-10901|dose escalation study, doses will vary per cohort. patients will receive an IV infusion weekly for two weeks every three weeks.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity |  | through cycle 1 | 
| Maximum tolerated dose |  | for the duration of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Qualitative and quantitative toxicities |  | for the duration of the study | 
| Pharmacokinetics |  | for the duration of the study | 
| Anti-tumor activity including overall response rate, time to progression and survival |  | for the duration of the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma