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A Phase II, Multi-center, Open-label, Randomized Study of Vorinostat Plus Lenalidomide and Dexamethasone or Lenalidomide Plus Dexamethasone in Multiple Myeloma Patients Who Experience Biochemical Relapse During Lenalidomide Maintenance Therapy


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

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Trial Information

A Phase II, Multi-center, Open-label, Randomized Study of Vorinostat Plus Lenalidomide and Dexamethasone or Lenalidomide Plus Dexamethasone in Multiple Myeloma Patients Who Experience Biochemical Relapse During Lenalidomide Maintenance Therapy


Inclusion Criteria:



- Age ≥ 18 years.

- Patient is, in the investigator(s) opinion, willing and able to comply with the
protocol requirements.

- Patient has given 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consent may be withdrawn by the patient at any time without prejudice to their future
medical care.

- Female patient is either post-menopausal for 24 consecutive months or surgically
sterilized or agree to continuous abstinence from heterosexual sexual contact or
willing to use effective contraception for 4 weeks prior to beginning study drug
therapy, during study drug therapy (including dose interruption) and for 4 weeks
after discontinuation of therapy; female patients not pregnant or nursing; female
with a negative pregnancy test.

- Male patient agrees to use an acceptable method for contraception during study drug
therapy (including dose interruption) and for 4 weeks after discontinuation of
therapy.

- Patient diagnosed with MM based on standard criteria, and has measurable disease
(14,15), defined as follows:

- Secretory myeloma: any quantifiable serum monoclonal protein value (generally, but
not necessarily, greater than 1 g/dL of IgG M-Protein and greater than 0.5 g/dL of
IgA M-Protein), and/or where applicable, urine light-chain excretion of > 200 mg/24
hours or involved free light chain (FLC) level > 10 mg/dl provided serum FLC ratio is
abnormal;

- Non-secretory myeloma: > 30% plasma cells in the bone marrow and at least one
plasmacytoma > 2 cm as determined by clinical examination or applicable radiographs
(i.e., MRI or CT scan).

- Patient receiving Lenalidomide maintenance therapy as part of first line treatment
(concomitant use of prednisone is accepted) and has experienced a biochemical
relapse, with evidence of progressive disease defined as increase of 25% from lowest
response value in any one or more of the following: Serum M-component (absolute
increase must be ≥ 0.5 g/100 ml) and/or Urine M-component (absolute increase must be
≥ 200 mg per 24 h); only in patients without measurable serum and urine M-protein
levels: the difference between involved and uninvolved FLC levels (absolute increase
must be > 10 mg/l) (12).

- No evidence of end organ damage that can be attributed to the underlying plasma cell
proliferative disorder, specifically hypercalcemia (serum calcium ≥ 11.5 mg/100 ml)
or renal insufficiency (serum creatinine > 1.73 mmol/l), or anemia (hemoglobin value
of > 2 g/100 ml below the lower limit of normal or a hemoglobin value < 10 g/100 ml)
or bone lesions (lytic lesions, severe osteopenia or pathologic fractures) (11).

- Patient has a Karnofsky performance status ≥ 60%.

- Patient has a life-expectancy > 3 months.

- Patient has not active infectious hepatitis type B or C and no known HIV infection.

- Patient has not to have congenital long QT syndrome or right bundle branch block +
left anterior hemiblock (bifascicular block).

Screening ECG with a QTc < 450 msec.

- Patient has not to take anti-arrhythmic drugs or other medicinal products which led
to QT prolongation and cumulative high dose of anthracycline.

- Patient has not clinically significant illness that would, in the investigator's
opinion, increase the patient's risk for toxicity.

- Patient has not a currently active malignancy, other than non melanoma skin cancer
and carcinoma in situ of the cervix. Patients are not considered to have a currently
active second malignancy if they have completed therapy for a prior malignancy, are
disease free from prior malignancies for > 5 years and are considered by their
physicians to be at less than 30% risk of relapse.

- No history of allergic reactions attributed to study agents.

- No prior exposure to HDACi. Patients exposed to valproic acid could be eligible with
a wash out period of at least 30 days.

- More than 30 days since prior class Ia, Ib and Ic antiarrhythmic medications.

- Patient has the following laboratory values within 28 days before baseline day 1 of
the cycle 1:

- Platelets count ≥ 75 x 109/L

- Absolute neutrophil count (ANC) ≥ 1.0 x 109/L

- Aspartate transaminase (AST), Alanine transaminase (ALT), total bilirubin: ≤ 2 x the
upper limit of normal (ULN).

- Calculated or measured creatinine clearance: ≥ 20 mL/minute

- PT and PTT: ≤ 1.5 the ULN

- Serum potassium ≥ LLN

- Serum magnesium ≥ LLN

- Serum phosphorus ≥ LLN

Exclusion Criteria:

- Any serious medical condition, laboratory abnormality, or psychiatric illness or
social situation that would prevent the subject from signing the informed consent
form or limit the compliance with study medications and requirements.

- Pregnant or beast feeding females.

- Use of any other concomitant standard/experimental anti-myeloma drug or therapy.

- Known positive for HIV or active infectious hepatitis, type B or C.

- Known congenital long QT syndrome or right bundle branch block + left anterior
hemiblock (bifascicular block).

- Screening ECG with a QTc > 450 msec.

- Ongoing therapy with anti-arrhythmic drugs or other medicinal products which led to
QT prolongation and cumulative high dose of anthracycline.

- Patient with currently active malignancy, other than non melanoma skin cancer and
carcinoma in situ of the cervix. Patients are not considered to have a currently
active second malignancy if they have completed therapy for a prior malignancy, are
disease free from prior malignancies for > 5 years and are considered by their
physicians to be at less then 30% risk of relapse.

- History of allergic reactions attributed to study agents.

- Prior exposure to HDACi. Patients exposed to valproic acid could be eligible with a
wash out period of at least 30 days.

- Less than 30 days since prior class Ia, Ib and Ic antiarrhythmic medications

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Rate of PR (PARTIAL RESPONSE) with the association of ZLd and Ld

Outcome Description:

Determine the rate of PR with the association of ZLd and Ld in patients who experience biochemical relapse during Lenalidomide maintenance therapy. ZLd and Ld: responses will be evaluated after the enrollment of 10 and 18 pts respectively. If ≤1 and ≤2 respectively responses will be observed the trial will be stopped. Otherwise 19 and 25 pts respectively will be enrolled: if ≤5 for Zld and ≤7 for Ld responses will be observed, no further investigation will be needed

Outcome Time Frame:

Responses will be evaluated after 112 days from enrollment of each patients (4 cycles of therapy)

Safety Issue:

Yes

Principal Investigator

Antonio Palumbo, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Division of Hematology, University of Turin, Italy

Authority:

Italy: Ethics Committee

Study ID:

UNITO-MM-01

NCT ID:

NCT01501370

Start Date:

January 2012

Completion Date:

February 2017

Related Keywords:

  • Multiple Myeloma
  • Myeloma
  • Biochemical relapse
  • Multiple Myeloma
  • Neoplasms, Plasma Cell

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