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A Phase I/II, Multicenter, Open-label, Dose-escalation Study of Bendamustine in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Refractory Multiple Myeloma

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Trial Information

A Phase I/II, Multicenter, Open-label, Dose-escalation Study of Bendamustine in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma


PRIMARY OBJECTIVES: I. To determine the MTD of bendamustine and lenalidomide in combination
with dexamethasone in subjects with MM in first or second relapse. (Phase I) II. To
evaluate the confirmed response rate of bendamustine in combination with lenalidomide and
dexamethasone in subjects with MM in first or second relapse. (Phase II) SECONDARY
OBJECTIVES: I. To evaluate the safety of bendamustine in combination with lenalidomide and
dexamethasone. (Phase I and II) II. To evaluate time-to-tumor-progression, progression-free
survival, duration of response, and overall survival. (Phase II) OUTLINE: This is a phase I
dose escalation study of bendamustine hydrochloride and lenalidomide followed by a phase II
study. Patients receive dexamethasone orally or IV on days 1, 8, 15, and 22; bendamustine
hydrochloride IV over 30 minutes on days 1 and 2; and oral lenalidomide once daily on days
1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or
unacceptable toxicity. Patients achieving at least stable disease after 6 courses may
continue to receive lenalidomide and dexamethasone as above in the absence of disease
progression or unacceptable toxicity. Dexamethasone may be discontinued after 12 courses of
therapy at the treating investigator's discretion. After completion of study treatment,
patients are followed at 4 weeks and then periodically for up to 2 years.

Inclusion Criteria


Inclusion:

- Diagnosis of MM and documentation of at least 1 prior therapy (induction therapy
followed by stem cell transplantation is considered one prior therapy) but not more
than two previous therapies

- Females of childbearing potential (FCBP) must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to
and again within 24 hours of starting lenalidomide

- Men must agree to use a latex condom during sexual contact with a FCBP even if they
have had a successful vasectomy; all patients must be counseled at a minimum of every
28 days about pregnancy precautions and risks of fetal exposure

- Ability to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use protected health information

- Able to take aspirin (325 mg) daily as prophylactic anticoagulation (patients
intolerant to ASA or at high risk of developing thrombosis may use warfarin or low
molecular weight heparin)

- AST (SGOT) and ALT (SGPT) =< 3.0 x upper limit of normal (ULN)

- Creatinine clearance >= 60 mL/min (Cockcroft-Gault calculation) for patients enrolled
in Phase 1 and Creatinine clearance >= 30 mL/min (Cockcroft-Gault calculation) for
patients enrolled in phase 2 portion

- Patients with measurable disease, defined by any of the following: serum monoclonal
protein >= 1.0 g by protein electrophoresis; > 200 mg of monoclonal protein in the
urine on 24-hour electrophoresis; serum immunoglobulin free light chain >= 10 mg/dL
AND abnormal serum immunoglobulin kappa to lambda free light chain ratio; or
monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)

- All necessary baseline studies for determining eligibility must be obtained within 21
days prior to enrollment

- Subject has an ECOG =< 2 OR Karnofsky >= 60% performance status; patients with lower
performance status based solely on bone pain secondary to multiple myeloma will be
eligible

- FCBP must either commit to continued abstinence from heterosexual intercourse or
begin two acceptable methods of birth control, one highly effective method and one
additional effective method AT THE SAME TIME, at least 28 days before she starts
taking lenalidomide; FCBP must also agree to ongoing pregnancy testing

- Absolute neutrophil count (ANC) >= 1,000 cells/dL (1.0 x 10^9/L) (growth factors
cannot be used within 14 days of first drug administration)

- Untransfused platelet count >= 75,000 cells/dL (50 x 10^9/L) for patients in whom <
50% of bone marrow nucleated cells are plasma cells; but platelet count >=50,000/dL
for patients in whom 50% of bone marrow nucleated cells are plasma cells

- Total Bilirubin =< 1.5 mg/dL

- Hemoglobin >= 8.0 g/dl

Exclusion:

- Diagnosed or treated for another malignancy within 3 years of enrollment, with the
exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy

- Patients may be receiving concomitant therapy with bisphosphonates and low dose
corticosteroids (e.g., prednisone up to but no more than 10 mg p.o. q.d. or its
equivalent) for symptom management and comorbid conditions; doses of corticosteroid
should be stable for at least 7 days prior to study treatment

- Prior radiation therapy within 2 weeks of the first dose of study treatment

- Known active infection requiring parenteral or oral anti-infective treatment

- Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or
confuse follow-up evaluation

- Patient has hypersensitivity to any of the components of study therapy - Known
HIV or active hepatitis B or C viral infection

- Known hypersensitivity to required prophylactic medications

- Patient has received other investigational drugs within 14 days before enrollment

- Pregnant or breast-feeding females (lactating females must agree not to breast feed
while taking lenalidomide)

- Subjects with evidence of mucosal or internal bleeding and/or platelet transfusion
refractory (i.e., unable to maintain a platelet count >= 50,000 cells/mm^3)

- Concurrent therapy with a marketed or investigational anticancer therapy

- Any medical conditions that, in the Investigator's opinion, would impose excessive
risk to the patient

- Other investigational agents are not to be used during the study

- Prior peripheral stem cell transplant within 12 weeks of the first dose of study
treatment

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Maximum tolerated dose of bendamustine hydrochloride and lenalidomide in combination with dexamethasone (phase I)

Safety Issue:

Yes

Principal Investigator

Shaji K. Kumar, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Food and Drug Administration

Study ID:

MMRC-020-021

NCT ID:

NCT01049945

Start Date:

February 2010

Completion Date:

Related Keywords:

  • Refractory Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell

Name

Location

Mayo ClinicRochester, Minnesota  55905
Mayo Clinic in FloridaJacksonville, Florida  32224
City of HopeDuarte, California  91010
University of ChicagoChicago, Illinois  60637
Washington Universtiy School of MedicineSt. Louis, Missouri  63110