Efficacy and Safety Study of 3 Thalidomide Doses for the Treatment of Relapsed Refractory Multiple Myeloma

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00452569
• Date of registration: 23/03/2007
• Prospective Registration: No
• Primary sponsor: Celgene
• Public title: Efficacy and Safety Study of 3 Thalidomide Doses for the Treatment of Relapsed Refractory Multiple Myeloma OPTIMUM
• Scientific title: Randomised, Controlled, Open-labelled, Multi-centre Comparison of Thalidomide Versus High-dose Dexamethasone for the Treatment of Relapsed Refractory Multiple Myeloma
• Date of first enrolment: February 1, 2006
• Target sample size: 499
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00452569
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Bulgaria, Croatia, Czech Republic, Czechia, Former Serbia and Montenegro, France, Germany, Hungary, India, Italy, Philippines, Poland, Portugal, Serbia, Slovakia, South Africa, United Kingdom

Contacts

• Name: Martin Kropff, MD
• Affiliation: Universitatsklinikum Munster

Key inclusion & exclusion criteria

Inclusion Criteria:

- Male or female patients, aged = 18 years at the time of signing the informed consent
form

- Patients who have been previously diagnosed with MM who have received between 1 & 3
prior lines of treatment for their disease, and who require therapy because of disease
progression

- Secretory MM with measurable levels of monoclonal protein in serum (> 10 g/L of IgG
M-protein or > 5 g/L of IgA M-protein) or urine (= 200 mg/ 24hours); Patient with the
following rare subclasses of the immunoglobulin: IgD, IgE, IgM can be included in the
study if the level of monoclonal protein in serum is > 5g/L or = 200 mg/24hours in
urine. As IgM immunoglobulin isotype can be related to Waldenstrom's
macroglobulinemia, it is important to distinguish and not include in the study
patients with Waldenstrom's macroglobulinemia.

- ECOG performance status of 0, 1, or 2

- Life expectancy >3months

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

- Women of child-bearing potential must agree to use 2 methods of contraception for at
least 4weeks before starting the therapy, during the Treatment Period, & for 4 weeks
after the last dose

- Males must agree to use barrier contraception (latex condoms) when engaging in
reproductive activity during the Treatment Period & for 4 weeks after the last dose

- Written, informed consent

Exclusion Criteria:

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the patient from signing the Informed Consent Form

- Pregnant or lactating women. A serum ß-hCG pregnancy test must be performed at the
Screening visit for female patients of child-bearing potential. If the test is
positive, the patient must be excluded from the study. Confirmation that the patient
is not pregnant must be established by a negative serum or urinary pregnancy test with
the result obtained 1day prior to the Baseline visit (or the day of the visit if
results are available before drug delivery). A pregnancy test is not required for
naturally post-menopausal women (who have not had menses at any time in the preceding
24 consecutive months) or surgically sterilized women (hysterectomy, bilateral
ovariectomy, bilateral salpingectomy)

- Non-secretory MM

- Any of the following laboratory abnormalities: Absolute neutrophil count (ANC) <500
cells/mm3 (0.5 x 109/L); Platelet count <30,000/mm3 (30.0 x 109L) without transfusion
support within 7 days before the test; Serum creatinine >3.0mg/dL (265µmol/L); Serum
aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) >3.0 x upper
limit of normal (ULN); Serum total bilirubin >2.0mg/dL (34µmol/L)

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

- Severe cardiac dysfunction (according to the New York Heart Association [NYHA]
classification III-IV)

- Severe bradycardia (<50bpm)

- Peripheral neuropathy =Grade 2 in severity (according to the NCI CTC Version 3.0)

- Prior history of malignancy (except for basal cell or squamous cell carcinoma of the
skin or carcinoma in situ of the cervix or breast) unless the patient has been free of
disease for =5years

- Patient received any chemotherapy, corticosteroids (> 10 mg/day prednisone or
equivalent as a continuous dose) within 4 weeks before randomization

- Previously treated with thalidomide or thalidomide derivatives

- Patients refractory to high-dose dexamethasone (defined as experiencing less than a PR
to dexamethasone, or PD within 6months after discontinuing dexamethasone, or
discontinued dexamethasone because of =Grade 3 dexamethasone-related toxicity.
Previous high-dose dexamethasone therapy is defined as >500mg dexamethasone or
equivalent over a 10week period, whether administered alone or as part of the VAD
regimen)

- Contraindications for high-dose dexamethasone

- Active or chronic gastrointestinal ulcers, active viral infections (herpes, varicella,
HIV, hepatitis B, hepatitis C), glaucoma, uncontrolled hypertension, or diabetes
mellitus, unless well controlled & under strict supervision during dexamethasone
treatment

- Patient enrolled in another clinical trial or who have participated in another trial
with the last 4weeks before randomization



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Myeloma

Intervention(s)

Drug: Dexamethasone

Drug: Thalidomide

Primary Outcome(s)

The evaluation of Independent Review Committee-documented time to progression (TTP). [Time Frame: >160 "IRC confirmed" disease progression in the Dexamethasone or Thalidomide 400 mg/day arms]

Secondary Outcome(s)

Response duration [Time Frame: Every 4 weeks]

Clinical benefit as measured by ECOG performance status, transfusion requirement and Grade =3 infections (assessed by the National Cancer Institute Common Toxicity Criteria) [Time Frame: Every 4 weeks]

Composite of disease progression and death (recurrent time(s) from randomisation to disease progression and/or death) [Time Frame: Evaluated after 160 "IRC confirmed" disease progression in the Dexamethasone or Thalidomide 400 mg/day arms]

Assessment of peripheral neuropathy [Time Frame: Screening, Week 24, Week 48]

Progression-free survival (PFS) [Time Frame: Disease progression evaluated every 4 weeks]

Adverse events (AEs) [Time Frame: Every 4 weeks]

Clinical laboratory tests [Time Frame: Every 4 weeks]

Response rate (CR + PR), according to the EBMT criteria [Time Frame: Every 4 weeks]

Overall survival (OS) [Time Frame: Evaluated after 150 deaths occurring in Dexamethasone and Thalidomide 400 mg arms]

Quality of life as determined by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) [Time Frame: Baseline/Week 8/ Week 16/Week 24/Week 32/Week 40/Week 48]

Vital signs and physical examination [Time Frame: Every 4 weeks]

Secondary ID(s)

THA PH INT 2005 CL001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors