BB-10901 in Treating Patients With Relapsed and/or Refractory Multiple Myeloma (IMGN901)

ImmunoGen

Status and phase

Completed

Phase 1

Conditions

Multiple Myeloma

Treatments

Drug: BB-10901

Study type

Interventional

Funder types

Industry

Identifiers

NCT00346255

IMMUNO-003

DFCI-05031

CDR0000491241

Details and patient eligibility

About

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.

Full description

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.

Enrollment

37 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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