Overview

Phase II Study of Subcutaneous (SC) Bortezomib, Lenalidomide and Dexamethasone for Relapsed and/or Refractory Multiple Myeloma; Followed by SC Bortezomib Maintenance

Status:
Withdrawn
Trial end date:
2015-06-26
Target enrollment:
0
Participant gender:
All
Summary
Background: Bortezomib is a drug approved by the Food and Drug Administration (FDA) to treat patients with multiple myeloma. It is given by intravenous injection. Lenalidomide is a drug that alters the immune system. It may also help suppress tumor growth. It is approved by the FDA to treat some types of blood cancers. Dexamethasone prevents or treats inflammation. It is sometimes used to treat multiple myeloma. Objectives: The purpose of this study examine how the combination of the study drugs affects myeloma. - Eligibility: - Participants at least 18 years old who have multiple myeloma that has come back, did not respond to treatment, or worsened while being treated. - Participants who may be pregnant will be tested to ensure that they are not pregnant. Design: - Participants will be screened with a history and physical examination. Blood work and urine samples will be taken. A series of x-rays of all bones will be done. A bone marrow biopsy will be done. - Treatment will be monitored with frequent blood tests and imaging studies. - Treatment will continue as long as the cancer does not grow or spread and no serious side effects develop. - There will be up to eight 21-day treatment cycles. - Bortezomib is given by subcutaneous (under the skin) (SC) injection on days 1, 4, 8, and 11 of the cycle. - Lenalidomide is given by mouth on days 1 14 of the cycle. - Dexamethasone is given by mouth on days 1, 2, 4, 5, 8, 9, 11, and 12 of the cycle. - Following cycle eight, if the disease is stable or better, participants will receive bortezomib SC at the dose given at the end of cycle eight. - Participants will take valacyclovir or acyclovir while taking bortezomib to prevent virus infections.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Cancer Institute (NCI)
Collaborator:
Millennium Pharmaceuticals, Inc.
Treatments:
BB 1101
Bortezomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Thalidomide
Criteria
- INCLUSION CRITERIA:

2.1.1.1 Relapsed and/or refractory histologically confirmed multiple myeloma as defined by:

1. Relapse from complete response with reappearance of the serum or urinary paraprotein,
more or equal than 5% bone marrow plasma cells, new lytic bone lesions and /or soft
tissue plasmacytomas, an increase in size of residual bone lesions and /or development
of hypercalcemia (corrected serum calcium >11.5 mg/dl) not attributable to another
cause.

2. Progressive disease: when a complete response has not been achieved, include new or
expanding bone lesions, hypercalcemia, and a >25% increase in serum monoclonal
paraprotein concentration, 24-hour urinary light chain excretion, or plasma cells
within the bone marrow.

3. Refractory disease: Unresponsiveness to current therapy or progressive disease within
60 days of prior treatment.

2.1.1.2 Measurable disease within the past 4 weeks defined by any one of the following:

1. Serum monoclonal protein greater than or equal to 1.0 g/dL

2. Urine monoclonal protein >200 mg/24 hour

3. Serum immunoglobulin free light chain > 10 mg/dL AND abnormal

kappa/lambda ratio (reference 0.26-1.65)

2.1.1.3 Creatinine Clearance greater than or equal to 60 ml/min. CrCl will be calculated by
Cockcroft-Gault method. CrCl (calculated) = (140 Age) times Mass (in kilograms) times [0.85
if Female] 72 times Serum Creatinine (in mg/dL). If calculated CrCl based on
Cockcroft-Gault method is < 60 mL/min, patient will have a 24 hr urine collection to
measure CrCl. The measured CrCl must also be greater than or equal to 60 ml/min for the
patient to be eligible.

2.1.1.4 Age > 18 years

2.1.1.5 Eastern Cooperative Oncology Group (ECOG) performance status 0-2

2.1.1.6 Female subject is either postmenopausal for at least 1 year before the screening
visit, is surgically sterilized or if they are of childbearing potential, agree to practice
2 effective methods of contraception from the time of signing the informed consent form
through 30 days after the last dose of VELCADE, or agree to completely abstain from
heterosexual intercourse.

2.1.1.7 Absolute neutrophil count (ANC) greater than or requal to 1.0 K/uL, hemoglobin
greater than or equal to 8 g/dL (transfusions are permissible), and platelet count greater
than or equal to 75K/uL within 7 days before enrollment.

2.1.1.8 Adequate hepatic function, with bilirubin < 1.5 times ULN; AST and ALT < 3.0 times
ULN

2.1.1.9 Patients must have completed prior treatments (except steroids) at least 30 days
before enrollment.

2.1.1.10 Prior allogeneic stem cell transplant without evidence of graft versus host
disease. (GVHD) will be eligible at the investigator s discretion.

2.1.1.11 Permitted concurrent systemic treatment for MM.

1. Treatment of hypercalcemia or spinal cord compression or aggressively progressing
myeloma with corticosteroids is permitted.

2. Bisphosphonates are permitted.

3. Radiotherapy is permitted. Enrollment of subjects who require concurrent radiotherapy
(which must be localized in its field size) should be deferred until the radiotherapy
is completed and 3 weeks have elapsed since the last date of therapy.

2.1.1.12 All study participants must be registered into the mandatory RevAssist
program, and be willing and able to comply with the requirements of RevAssist .

2.1.1.13 Females of childbearing potential (FCBP) (Cross) must have a negative serum
beta-human chorionic gonadotropin (beta-hCG) or urine pregnancy test within 10 14 days
and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions
must be filled within 7 days) and 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. Men must agree to use a latex condom during sexual contact with a FCBP even
if they have had a successful vasectomy.

2.1.1.14 Male subjects, even if surgically sterilized (ie, status prostatectomy) must
agree to 1 of the following: practice effective barrier contraception during the
entire study treatment period and through a minimum of 30 days after the last dose of
study drug, or completely abstain from heterosexual intercourse.

2.1.1.15 Subjects must be able to give voluntary written informed consent before
performance of any study-related procedure not part of normal medical care, with the
understanding that consent may be withdrawn by the subject at any time without
prejudice to future medical care.

2.1.1.16 Known HIV infected patients meeting the following characteristics are
eligible:

- CD4 cell count greater than or equal to 334/mm(3)

- Meeting either of the following:

- Willing to suspend antiretroviral therapy for duration of protocol therapy or

- On stable regimen of combination antiretroviral therapy that does not include
either zidovudine or stavudine for at least 12 weeks and without evidence of
toxicity

EXCLUSION CRITERIA:

2.1.2.1 Refractory to lenalidomide and/or bortezomib in the most recent line of
therapy

2.1.2.2 Prior allogeneic stem cell transplant if the patient has graft versus host
disease (GVHD).

2.1.2.3 Plasma cell leukemia

2.1.2.4 Pregnant or lactating females. Confirmation that the subject is not pregnant
must be established by a negative serum <=-human chorionic gonadotropin (beta hCG)
pregnancy test result obtained during screening. Pregnancy testing is not required for
postmenopausal or surgically sterilized women.

2.1.2.5 Female patients who are lactating or have a positive serum pregnancy test
during the screening period, or a positive urine pregnancy test on Day 1 before first
dose of study drug, if applicable.

2.1.2.6 Uncontrolled hypertension or diabetes

2.1.2.7 Active hepatitis B or C infection

2.1.2.8 Patient had myocardial infarction within 6 months prior to enrollment or has
New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina,
severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities. Prior to study entry, any ECG
abnormality at screening must be documented by the investigator as not medically
relevant.

2.1.2.9 Has refractory GI disease with refractory nausea/vomiting, inflammatory bowel
disease, or bowel resection that would prevent absorption

2.1.2.10 Uncontrolled intercurrent illness including but not limited to active
infection or psychiatric illness/social situations that would compromise compliance of
study requirements

2.1.2.11 Significant neuropathy greater than or equal to Grade 1 with pain or Grade 2
at the time of first dose or within 14 days of enrollment.

2.1.2.12 Contraindication to any concomitant medication, including antivirals,
anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to
therapy

2.1.2.13 Active infection requiring treatment within two weeks prior to first dose

2.1.2.14 Major surgery within 1 month prior to enrollment

2.1.2.15 Hypersensitivity to bortezomib, boron, mannitol or lenalidomide

2.1.2.16 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.

2.1.2.17 Participation in clinical trials with other investigational agents not
included in this trial, within 14 days of the start of this trial and throughout the
duration of this trial.