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

NCT01212952 | Completed Phase 1 Results DMC

• 4 other identifiers: MC1082NCI-2010-0196710-001545PO-MM-PI-0019
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Find Maximum Tolerated Dose (MTD) of Bortezomib in Combination With Pomalidomide and Dexamethasone Out to 2.5 Years, by Count of Patients With Dose Limiting Toxicities.

  MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).

  2.5 years

• Number of Participants With a Hematologic Response (PR, VGPR, or CR)

  The number of participants who achieve PR, VGPR, or CR as defined by The International Myeloma Working Group uniform response criteria(2011). sCR: CR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \> 90% reduction in serum M-protein plus urine M-protein level \< 100 mg/24 h. PR: \> 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or to \< 200 mg/24 h. MR: NA. SD: Not meeting criteria for CR, VGPR, PR, or progressive disease. PD: Increase of \> 25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be \> 0.5 g/dL), Urine M-component and/or (the absolute increase must be \> 200 mg/24 h)

  2.5 years

Secondary Outcomes (2)

• Progression Free Survival

  2.5 years

• Number of Participants With Adverse Events

  2.5 years

Study Arms (1)

Arm I

EXPERIMENTAL

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; Drug: bortezomib; Drug: dexamethasone; Other: laboratory biomarker analysis; Other: gene expression analysis

Interventions

pomalidomide DRUG

Given orally

Also known as: CC-4047

Arm I

bortezomib DRUG

Given IV

Also known as: LDP 341, MLN341, PS-341, VELCADE

Arm I

dexamethasone DRUG

Given orally

Also known as: Aeroseb-Dex, Decaderm, Decadron, Decaspray, DM, DXM

Arm I

laboratory biomarker analysis OTHER

Optional correlative studies

Arm I

gene expression analysis OTHER

Optional correlative studies

Arm I

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Paludo J, Mikhael JR, LaPlant BR, Halvorson AE, Kumar S, Gertz MA, Hayman SR, Buadi FK, Dispenzieri A, Lust JA, Kapoor P, Leung N, Russell SJ, Dingli D, Go RS, Lin Y, Gonsalves WI, Fonseca R, Bergsagel PL, Roy V, Sher T, Chanan-Khan AA, Ailawadhi S, Stewart AK, Reeder CB, Richardson PG, Rajkumar SV, Lacy MQ. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed lenalidomide-refractory multiple myeloma. Blood. 2017 Sep 7;130(10):1198-1204. doi: 10.1182/blood-2017-05-782961. Epub 2017 Jul 6.

  PMID: 28684537 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pomalidomide; Bortezomib; Dexamethasone; Calcium Dobesilate; Gene Expression Profiling

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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Genetic Techniques; Investigative Techniques

Results Point of Contact

• Title: Martha Q. Lacy, M.D.
• Organization: Mayo Clinic

lacy.martha@mayo.edu

(507) 284-8430

Study Officials

• Martha Lacy, M.D.

  Mayo Clinic

  STUDY CHAIR

• Joseph R. Mikhael, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Vivek Roy, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2010
• First Posted: October 1, 2010
• Study Start: September 1, 2011
• Primary Completion: August 15, 2017
• Study Completion: March 22, 2018
• Last Updated: April 17, 2020
• Results First Posted: April 17, 2020

Record last verified: 2019-02

Locations

US (3)