Pomalidomide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01212952
First received: September 29, 2010
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

RATIONALE: Pomalidomide and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bortezomib may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pomalidomide and bortezomib together with dexamethasone may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib when given together with pomalidomide and dexamethasone and to see how well it works in treating patients with relapsed or refractory multiple myeloma.


Condition Intervention Phase
Refractory Multiple Myeloma
Drug: pomalidomide
Drug: bortezomib
Drug: dexamethasone
Other: laboratory biomarker analysis
Other: gene expression analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: MC1082: A Phase I/II Trial of Pomalidomide (CC-4047), Bortezomib, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of bortezomib in combination with pomalidomide and dexamethasone out to 2.5 years. [ Time Frame: 2.5 years ] [ Designated as safety issue: Yes ]
  • Hematologic response rate (PR, VGPR, or CR) of pomalidomide, bortezomib and dexamethasone in patients with relapsed or refractory myeloma out to 2.5 years [ Time Frame: 2.5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to progression. [ Designated as safety issue: No ]
  • Toxicity of pomalidomide, bortezomib and dexamethasone in this patient population. [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 61
Study Start Date: September 2011
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral pomalidomide on days 1-21; bortezomib IV on days 1, 8, 15, 22; and oral dexamethasone on days 1, 8, 15, 22. Treatment repeats every 28 days for 8 courses. Patients then receive maintenance therapy comprising oral pomalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: pomalidomide
Given orally
Other Name: CC-4047
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • PS-341
  • VELCADE
Drug: dexamethasone
Given orally
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • Decaspray
  • DM
  • DXM
Other: laboratory biomarker analysis
Optional correlative studies
Other: gene expression analysis
Optional correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of bortezomib in combination with pomalidomide and dexamethasone.

II. To evaluate the hematologic response rate (PR, VGPR, or CR) of pomalidomide, bortezomib and dexamethasone in patients with relapsed or refractory myeloma.

SECONDARY OBJECTIVES:

I. Time to progression.

II. To assess the toxicity of pomalidomide, bortezomib and dexamethasone in this patient population.

OUTLINE : This is a phase I, dose-escalation study of bortezomib followed by a phase II study. Patients receive oral pomalidomide on days 1-21; bortezomib IV on days 1, 8,15, 22; and oral dexamethasone on days 1, 8, 15, 22 . Treatment repeats every 28 days for 8 courses. Patients then receive maintenance therapy comprising oral pomalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Serum Creatinine =< 3 mg/dL
  • Absolute neutrophil count >= 1000/uL
  • Platelet count >= 75,000/uL
  • Measurable disease of multiple myeloma as defined by at least ONE of the following:

    • serum monoclonal protein >= 1.0 g/dL
    • > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
    • serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
    • monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)
    • measurable plasmacytoma that has not been radiated
  • ECOG Performance status (PS) 0, 1, or 2
  • Previously treated relapsed or refractory multiple myeloma
  • Patients must have received at least one prior therapy but no more than 4 therapies.

    • one or more of the prior regimens must have included lenalidomide and it has been determined the patient is refractory, resistant, or relapsed this therapy
    • prior bortezomib not required but if prior exposure, patients should not be refractory (Refractory means progression on therapy or within 60 days from the last dose of bortezomib.)
  • Provide informed written consent
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide; FCBP must also agree to ongoing pregnancy testing
  • Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy
  • All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • Willing and able to take aspirin or alternate prophylactic anticoagulation
  • All previous cancer therapy, including chemotherapy, high dose corticosteroids, immune modulatory drugs or proteosome inhibitors must have been discontinued >= 2 weeks prior to study registration
  • Any prior treatment with investigational agents must be discontinued >= 28 days prior to study registration
  • Willing to abstain from donating blood during study participation and for 28 days after discontinuation of study drug
  • Men must agree to abstain from donating semen or sperm during study participation and for 28 days after discontinuation of study drug
  • Willingness to return to enrolling institution for follow-up

Exclusion Criteria:

  • Concomitant high dose corticosteroids (concurrent use of corticosteroids); EXCEPTION: Patients may be on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if they are being given for disorders other than myeloma, i.e., adrenal insufficiency, rheumatoid arthritis, etc
  • Another malignancy undergoing active treatment with the exception of non melanoma skin cancer or in situ cervical or breast cancer
  • Pregnant women or women of reproductive ability who are unwilling to use effective contraception
  • Nursing women
  • Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment
  • Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
  • Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational: NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
  • Active DVT or PE that has not been therapeutically anticoagulated
  • Known positive for HIV or active hepatitis infection
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Known hypersensitivity to thalidomide or lenalidomide including development of erythema nodosum if characterized by a desquamating rash
  • > grade 2 peripheral neuropathy
  • Any prior use of pomalidomide
  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: NCT01212952

Locations
United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States
Contact: Mayo Clinic Clinical Trials Office    507-538-7623      
Principal Investigator: Joseph R. Mikhael, M.D.         
United States, Florida
Mayo Clinic in Florida Recruiting
Jacksonville, Florida, United States
Contact: Mayo Clinic Clinical Trials Office    507-538-7623      
Principal Investigator: Vivek Roy, M.D.         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mayo Clinic Clinical Trials Office    507-538-7623      
Principal Investigator: Martha Q. Lacy, M.D.         
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Martha Lacy, M.D. Mayo Clinic
Principal Investigator: Joseph R. Mikhael, M.D. Mayo Clinic in Arizona
Principal Investigator: Vivek Roy, M.D. Mayo Clinic in Florida
  More Information

No publications provided

Responsible Party: Martha Q. Lacy, M.D., Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT01212952     History of Changes
Other Study ID Numbers: MC1082, NCI-2010-01967, 10-001545, PO-MM-PI-0019, MC1082
Study First Received: September 29, 2010
Last Updated: March 4, 2014
Health Authority: United States: Federal Government

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
Bortezomib
Pomalidomide
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

ClinicalTrials.gov processed this record on August 28, 2014