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

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

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.

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.

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