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

Multiple Myeloma Clinical Trial

— IMGN901  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00346255
• Other study ID #: CDR0000491241
• Secondary ID: IMMUNO-003DFCI-0
• Status: Completed
• Phase: Phase 1
• First received: June 28, 2006
• Last updated: April 22, 2013
• Start date: April 2005
• Est. completion date: March 2011

Study information

• Verified date: April 2013
• Source: ImmunoGen, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00625508

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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

Locations

Country	Name	City	State
Argentina	Gascon 450 - (C1181ACH)	Buenos Aires	Capital Federal
Argentina	Juan Domingo Peron 1500 - (B1629AHJ) Pilar	Buenos Aires
Argentina	Av. Naciones Unidas 346. (X5016KEH)-Barrio Parque Velez Sarfield	Córdoba
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Cedars-Sinai Outpatient Cancer Center	Los Angeles	California
United States	St. Vincent's Comprehensive Cancer Center - Manhattan	New York	New York
United States	UCSF	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
ImmunoGen, Inc.

Countries where clinical trial is conducted

United States,  Argentina, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity		through cycle 1	Yes
Primary	Maximum tolerated dose		for the duration of the study	Yes
Secondary	Qualitative and quantitative toxicities		for the duration of the study	Yes
Secondary	Pharmacokinetics		for the duration of the study	No
Secondary	Anti-tumor activity including overall response rate, time to progression and survival		for the duration of the study	No