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An Open Label Phase I/II Study of the Safety and Efficacy of Cyclophosphamide, Bortezomib (VELCADE), Pegylated Liposomal Doxorubicin (DOXIL), and Dexamethasone, (CVDD) in Newly Diagnosed Patients With Multiple Myeloma


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Multiple Myeloma

Thank you

Trial Information

An Open Label Phase I/II Study of the Safety and Efficacy of Cyclophosphamide, Bortezomib (VELCADE), Pegylated Liposomal Doxorubicin (DOXIL), and Dexamethasone, (CVDD) in Newly Diagnosed Patients With Multiple Myeloma


The first cohort of 3 participants enrolled into Phase I of the study will receive dose
level 1. A full safety evaluation will be conducted when these participants have completed
one cycle (21 days) of combination therapy. Further patient accrual will be suspended while
the safety data is evaluated at each dose level.

Dose escalation for subsequent patients will proceed through dose levels 2, 3 and 4 as
follows:

- If no dose limiting toxicity (DLT) is reported in the first 3 participants at a dose
level, that dose level will be considered safe and 3 participants will be enrolled at
the next dose level. If 1/3 participants in a cohort at a dose level has a DLT, the
dose level will be expanded to obtain 6 evaluable participants.

- If > 1 of 3 participants in a cohort experience DLT, that dose level will not be
considered safe. No further dose escalation will take place, and the immediate lower
dose level will be considered the maximum tolerated dose (MTD) if 6 patients had been
enrolled at that dose level. Otherwise, expand the immediate lower dose level to 6
evaluable patients*.

- If there are < 2 participants with a DLT among the expanded cohort of 6 evaluable
participants, a cohort of 3 participants will be enrolled in the next higher dose
level.

- If there are 2 or more participants with a DLT among the expanded cohort of 6 evaluable
participants, that dose level will not be considered safe. No further dose escalation
will take place, and the immediate lower dose level will be considered the MTD if 6
patients had been enrolled at that dose level. Otherwise, expand the immediate lower
dose level to 6 evaluable patients*.

- * If DLT occurs in no more than 1 patient in the expanded dose cohort, then that dose
level will be considered MTD. Otherwise, the dose will be further de-escalated in a
similar fashion until the MTD is reached.


Inclusion Criteria:



- Understand and voluntarily sign informed consent form; equal to or greater than 18
years of age at time of consent

- Able to adhere to the study visit schedule and other protocol requirements

- Diagnosed active multiple myeloma

- Measurable myeloma paraprotein levels in serum (≥ 0.5 g/dL) or urine (≥ 0.2 g
excreted in a 24-hour urine collection sample), or serum involved free light chains (
>10mg/dl) provided that the k/l ratio is abnormal

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

- Performance status of 3 allowed if related to bony disease.

- Bilirubin ≤ 1.5x upper limits of normal (ULN)

- Liver enzymes: alanine transaminase (ALT)or aspartic transaminase (AST) ≤ 2.5 x ULN.
In the presence of liver metastases, AST / ALT, alkaline phosphatase and total
bilirubin must not exceed 3x upper limit of normal (i.e.: must be ≤ 3x ULN).

- Adequate bone marrow function:

- Absolute neutrophil count (ANC) ≥ 1,000 cells/mm³ (1.0 x 10^9/L). Patients with bone
marrow >50% plasma cells are permitted to have a neutrophil count of < 1,000
cells/mm³.

- Platelets ≥ 100,000 cells/mm³. Patients with bone marrow >50% plasma cells are
permitted to have a Platelet count ≤ 100, 000 cells/mm³

- Hemoglobin > 8 g/dL (transfusion allowed to increase the Hgb)

- Adequate renal function: Creatinine ≤ 2.5 mg/dL

- Must have 2-d echocardiogram or multigated acquisition (MUGA) scan indicating left
ventricular ejection fraction (LVEF) ≥ 50% within 42 days prior to first dose of
study drug. A MUGA scan or 2- d Echocardiogram may be used, but the same test must be
used throughout study) to evaluate LVEF.

- Women of childbearing potential(WCBP)† must have negative serum or urine pregnancy
test 10 to 14 days prior to starting therapy. Patients with reproductive potential
must use an adequate contraceptive method during treatment and for 3 months after
completing treatment. In addition, sexually active WCBP must agree to use adequate
contraceptive methods per the requirements outlined in protocol document.

- Patients treated with local radiotherapy with or without concomitant exposure to
steroids, for pain control or management of cord/nerve root compression, are
eligible. 4 weeks must have lapsed since last date of radiotherapy. Patients who
require concurrent radiotherapy should have entry to the protocol deferred until
radiotherapy is completed and 4 weeks have passed since last date of therapy.

Exclusion Criteria:

- Ongoing severe infection requiring intravenous antibiotic treatment

- Life expectancy < 3 months

- Prior malignancy, except; adequately treated basal cell or squamous cell skin cancer,
in-situ cervical cancer, or other cancer from which the participant has been
disease-free for at least 5 years. Concurrent prostate cancer for which patient is
receiving therapy will not be considered an exclusion if prostatic specific antigen
(PSA) has been stable for 3 years.

- Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma
cell dyscrasia

- Patients receiving therapeutic dosages of steroids for multiple myeloma

- Myocardial infarct within 6 months before enrollment, New York Heart Association
(NYHA) Class II or greater heart failure, uncontrolled angina, severe uncontrolled
ventricular arrhythmias, clinically significant pericardial disease, or
electrocardiographic evidence of acute ischemic or active conduction system
abnormalities

- Uncontrolled medical problems such as diabetes mellitus, coronary artery disease,
hypertension, unstable angina, arrhythmias, pulmonary, hepatic and renal diseases
unless renal insufficiency is felt to be secondary to multiple myeloma

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the patient from signing the informed consent form

- Pregnant or breast-feeding females. Lactating females must agree not to breast-feed.

- Any condition, including the presence of laboratory abnormalities, which places the
participant at unacceptable risk if he/she were to participate in the study or
confounds the ability to interpret data from the study.

- Prior chemotherapy for multiple myeloma, except for radiation to symptomatic bony
disease, plasmapheresis for hyperviscosity, kyphoplasty and/or vertebroplasty

- History of hypersensitivity reactions attributed to a conventional formulation of
doxorubicin hydrochloride (HC1) or the components of DOXIL®

- Prior anthracycline dose exceeding 360 mg/m² for doxorubicin (including DOXIL) or 720
mg/m² for epirubicin

- Grade 2 or higher peripheral neuropathy on clinical examination within 14 days before
enrollment

- Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes
(POEMS) syndrome or plasma cell leukemia

- Hypersensitivity to bortezomib, boron or mannitol

- Has received other investigational drugs within 14 days before enrollment

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Phase I - Maximum Tolerated Dose (MTD)

Outcome Description:

The primary objective of this phase is to determine the maximum tolerated dose of cyclophosphamide when given in combination with VELCADE, DOXIL and Dexamethasone (CVDD) in patients with newly diagnosed active multiple myeloma.

Outcome Time Frame:

12 months from last enrollment date

Safety Issue:

Yes

Principal Investigator

Melissa Alsina, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute

Authority:

United States: Institutional Review Board

Study ID:

MCC-15399

NCT ID:

NCT00750815

Start Date:

September 2008

Completion Date:

May 2013

Related Keywords:

  • Multiple Myeloma
  • B Cell
  • hematologic malignancy
  • plasma
  • bone marrow
  • Multiple Myeloma
  • Neoplasms, Plasma Cell

Name

Location

H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida  33612