A Combination of Zarnestra With Velcade for Patients With Relapsed Multiple Myeloma

NCT00361088 | Terminated Phase 1 DMC

• 2 other identifiers: MCC-139717032
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

In Phase I, patients will receive a combination of PS-341 (Velcade) and R115777 (Zarnestra) to determine the dose limiting toxicity (DLT). Once DLT is determined, patients in Phase II will be receive the maximum tolerated dose (MTD) to complete 8 cycles of therapy. Treatment will continue if there is evidence of continued response for 8 cycles. Patients will receive follow up to include normal laboratory evaluations at least every 3 months and a skeletal survey will be performed at least every 6 months.

Conditions

Multiple Myeloma

Keywords

Velcade (PS-341); Bortezomib; Zarnestra (R115777); Tipifarnib

Outcome Measures

Primary Outcomes (4)

• Dose Limiting Toxicity (DLT)

  Determine the dose limiting toxicity at 3 weeks post treatment

  Average of 6 months

• Maximum Tolerated Dose

  Determine the maximum tolerated dose

  Average of 6 months

• Response Rates

  Determine response rates after 8 cycles of treatment

  Average of 6 months

• Toxicity

  Determine toxicity profiles

  Average of 6 months

Secondary Outcomes (1)

• Progression Free Survival

  Average of 12 months

Study Arms (2)

Phase I

EXPERIMENTAL

Drug: PS-341; Drug: R11577

Phase II

EXPERIMENTAL

Drug: PS-341; Drug: R11577

Interventions

PS-341 DRUG

Phase I and II: 1.3mg/m2 iv days 1,4,8,11

Also known as: bortezomib, Velcade®

Phase I; Phase II

R11577 DRUG

Phase I: 100mg po BID days 1014 for Cohort 1, 200mg po BID days 1014 for Cohort 2, 300mg po BID days 1014 for Cohort 3. Phase II: Maximum Tolerated Dose (MTD)

Also known as: Zarnestra

Phase I; Phase II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary written informed consent
• Female subject is either post-menopausal/surgically sterilized or willing to use an acceptable method of birth control for the duration of the study.
• Male subject agrees to use an acceptable method for contraception for the duration of the study.
• Diagnosis of stage II or III multiple myeloma and have relapsed after at least one prior therapies confirmed by the presence of:
• A new lytic lesion
• A 25% increase in urine or serum monoclonal protein
• Patient can have received PS-341 (Velcade) previously and does not require a previous response.
• Patients must have measurable disease. One or more of the following must be present to qualify for this study:
• Serum M-component greater than or equal to 1.0 gm/dl (10.0 g/L) by serum protein electrophoresis
• Urine M-protein excretion \> 200 mg/24 (0.2 g/24h) hours, by urine protein electrophoresis
• Abnormal serum free light chain ratio with elevated Kappa or Lambda light chains in serum
• Baseline measurements must be done within 21 days of study entry.
• Karnofsky Performance Status Scale \> 60.
• Greater than or equal to 18 years of age.
• Expected survival of greater than 8 weeks.

You may not qualify if:

• Previously treated with R115777 (Zarnestra).
• Undergone an allogeneic bone marrow transplant.
• A platelet count of \<100,000 x 10 to the 9 power/L within 14 days before enrollment.
• Absolute neutrophil count of \<1.0 x 10 to the 9 power/L within 14 days before enrollment.
• Measured creatinine \> 1.5 X the upper limits of normal within 14 days before enrollment.
• Greater than or equal to Grade 2 peripheral neuropathy within 14 days before enrollment.
• Hypersensitivity to bortezomib, boron, mannitol or imidazole compounds
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening.
• Received other investigational drugs within 14 days of enrollment or immunotherapy within 30 days of enrollment.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Ongoing radiation therapy or radiation therapy within 14 days prior to first treatment.
• Cytotoxic chemotherapy within 30 days prior to first treatment.
• Therapy with high-dose corticosteroids within 14 days prior to first treatment.
• Presence of any of the following excludes a patient from entering the study until such condition is resolved (determined within 14 days prior to the first treatment):
• Elevated total bilirubin \> 2mg/dl, or direct bilirubin \> 2 times the ULN.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; tipifarnib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Melissa Alsina, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 3, 2006
• First Posted: August 7, 2006
• Study Start: August 1, 2005
• Primary Completion: June 1, 2007
• Study Completion: June 1, 2007
• Last Updated: November 25, 2013

Record last verified: 2011-05

Locations

US (1)