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

This study has been completed.
Sponsor:
Information provided by:
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00452569
First received: March 23, 2007
Last updated: March 27, 2013
Last verified: September 2009
  Purpose

The primary objective is to compare the time to progression (TTP) of three daily doses of thalidomide (100, 200 and 400 mg) with high-dose dexamethasone in relapsed refractory multiple myeloma (MM) patients and to subsequently select the optimum thalidomide dose in terms of median TPP and toxicity.


Condition Intervention Phase
Multiple Myeloma
Drug: Thalidomide
Drug: Dexamethasone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomised, Controlled, Open-labelled, Multi-centre Comparison of Thalidomide Versus High-dose Dexamethasone for the Treatment of Relapsed Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate (CR + PR), according to the EBMT criteria [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
  • Response duration [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) [ Time Frame: Disease progression evaluated every 4 weeks ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: Evaluated after 150 deaths occurring in Dexamethasone and Thalidomide 400 mg arms ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Adverse events (AEs) [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]
  • Assessment of peripheral neuropathy [ Time Frame: Screening, Week 24, Week 48 ] [ Designated as safety issue: Yes ]
  • Vital signs and physical examination [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]
  • Clinical laboratory tests [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 499
Study Start Date: February 2006
Study Completion Date: January 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Oral thalidomide (100mg/day) administered to the patient once daily until progression of the disease and for a maximum of 336 +/- 36 days (12 cycles of 28 +/- 3 days).
Drug: Thalidomide
Oral thalidomide (100mg or 200mg or 400 mg/day) administered to the patient once daily until progression of the disease and for a maximum of 336 + 36 days (12 cycles of 28 +/- 3 days).
Experimental: B
Oral thalidomide (200mg/day) administered to the patient once daily until progression of the disease and for a maximum of 336 +/- 36 days (12 cycles of 28 +/- 3 days).
Drug: Thalidomide
Oral thalidomide (100mg or 200mg or 400 mg/day) administered to the patient once daily until progression of the disease and for a maximum of 336 + 36 days (12 cycles of 28 +/- 3 days).
Experimental: C
Oral thalidomide (400mg/day) administered to the patient once daily until progression of the disease and for a maximum of 336 +/- 36 days (12 cycles of 28 +/- 3 days).
Drug: Thalidomide
Oral thalidomide (100mg or 200mg or 400 mg/day) administered to the patient once daily until progression of the disease and for a maximum of 336 + 36 days (12 cycles of 28 +/- 3 days).
Active Comparator: D
High dose oral dexamethasone will be administered at a dose of 40mg/day on days 1-4, 9-12 and 17-20 of each 28-day cycle for cycles 1-4. Beginning with cycle 5, the oral dexamethasone dosing schedule will be reduced to 40mg/day on days 1-4 of each 28-day cycle. Dexamethasone will be administered until progression of the disease and for a maximum of 336 +/- 36 days (12 cycles of 28 +/- 3 days).
Drug: Dexamethasone
High dose oral dexamethasone will be administered at a dose of 40mg/day on days 1-4, 9-12 and 17-20 of each 28-day cycle for cycles 1-4. Beginning with cycle 5, the oral dexamethasone dosing schedule will be reduced to 40mg/day on days 1-4 of each 28-day cycle. Dexamethasone will be administered until progression of the disease and for a maximum of 336 +/- 36 days (12 cycles of 28 +/- 3 days).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 β-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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00452569

  Show 86 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Principal Investigator: Martin Kropff, MD Universitatsklinikum Munster
  More Information

No publications provided by Celgene Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Elisabeth Kueenburg, Medical Project Director Multiple Myeloma, Celgene Corporation
ClinicalTrials.gov Identifier: NCT00452569     History of Changes
Other Study ID Numbers: THA PH INT 2005 CL001
Study First Received: March 23, 2007
Last Updated: March 27, 2013
Health Authority: European Union: European Medicines Agency

Keywords provided by Celgene Corporation:
Relapsed Refractory Multiple Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on July 31, 2014