Cyclophosphamide, Carfilzomib, Thalidomide, and Dexamethasone in Treating Patients With Newly Diagnosed Active Multiple Myeloma

NCT01057225 | Completed Phase 1 Results DMC

• 4 other identifiers: MC0982NCI-2009-01699PT-171-50209-004091
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Thalidomide may stop the growth of cancer cells by blocking blood flow to the tumor. Giving combination chemotherapy together with carfilzomib and thalidomide may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of carfilzomib when given together with cyclophosphamide, thalidomide, and dexamethasone in treating patients with newly diagnosed active multiple myeloma.

Conditions

Multiple Myeloma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (Phase I)

  To establish the maximum tolerated dose of carfilzomib given in combination with oral cyclophosphamide and thalidomide and dexamethasone. For this protocol, dose-limiting toxicity (DLT) will be defined as an adverse event attributed (definitely, probably, possibly) in the first or second cycle for patients enrolled to Dose Levels -1 and 0 and in the first cycle only for patients enrolled to Dose Levels 1 and 2. We are reporting the number of DLTs

  From baseline to end of active treatment, up to 12 28-day cycles.

• Percentage of Patients Who Have at Least a Confirmed Very Good Partial Response (Phase II)

  The proportion of patients who have at least a confirmed very good partial response will be calculated by taking the number of patients with a very good partial response or a complete response divided by the total number of patients. A complete response is defined as: * Negative immunofixation of the serum and urine * If at on study, only the measurable non-bone marrow parameter was FLC, normalization of FLC ratio * \< 5% plasma cells in bone marrow * Disappearance of any soft tissue plasmacytomas A very good partial response is defined as: * Serum and urine M-component detectable by immunofixation but not on electrophoresis or * If at on study, serum measurable, ≥ 90% or greater reduction in serum Mcomponent * Urine M-component \<100 mg per 24 hour

  Following the first 4 cycles of treatment (28 day cycles)

Secondary Outcomes (9)

• Progression-free Survival (Phase II)

  From baseline to progression or death up to 3 years

• Time to Treatment Failure

  From baseline to end of active treatment

• Stem Cell Collection and Engraftment (Phase II)

  Following the first 4 courses of treatment

• Complete Response (Phase II)

  Following the first 4 courses of treatment

• Survival Time (Phase II)

  From baseline to death

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive carfilzomib IV on days 1, 2, 8, 9, 15, and 16; oral cyclophosphamide on days 1, 8, and 15; oral dexamethasone on days 1, 8, 15, and 22; and oral thalidomide on days 1-28.

Drug: carfilzomib; Drug: cyclophosphamide; Drug: thalidomide; Drug: dexamethasone

Interventions

carfilzomib DRUG

Given IV

Also known as: PR-171

Arm I

cyclophosphamide DRUG

Given orally

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana, Enduxan

Arm I

thalidomide DRUG

Given orally

Also known as: alpha-phthalimidoglutarimide, Contergan, Kevadon, Synovir, THAL, Thalomid

Arm I

dexamethasone DRUG

Given orally

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

Arm I

Eligibility Criteria

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

You may qualify if:

• Creatinine =\< 2 mg/dL
• Calculated Creatinine Clearance \>= 30 mL/min
• Total Bilirubin =\< 2.0 mg/dL
• Alkaline Phosphatase =\< 3 x ULN
• ALT =\< 3 x ULN
• Absolute neutrophil count \>= 1000/uL
• Platelet \>= 75000/uL
• Hemoglobin \>= 8.0 g/dL
• Untreated symptomatic myeloma: Prior non-systemic therapy for the treatment of solitary plasmacytoma is permitted, but \>= 1 month should have elapsed from the last day of radiation; prior therapy with clarithromycin, DHEA, anakinra, pamidronate or zoledronic acid is permitted; any additional agents not listed must be approved by the Principal Investigator
• Prior high dose corticosteroid therapy for twelve days (480 mg total dose) or less is permitted for emergent complications from newly diagnosed multiple myeloma
• Measurable disease of multiple myeloma, as defined by at least ONE of the following:
• Serum monoclonal protein \>= 1.0 g by protein electrophoresis
• OR \> 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
• OR serum immunoglobulin free light chain \>= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio; OR monoclonal bone marrow plasmacytosis \>= 30% (evaluable disease)
• ECOG performance status (PS) 0, 1, 2; ECOG PS of 3 will be allowed if secondary to pain in the opinion of the Investigator

You may not qualify if:

• MGUS or smoldering myeloma
• Peripheral sensory neuropathy \>= Grade 2 as defined by CTEP Active Version of the CTCAE
• Active malignancy 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
• Known hypersensitivity, allergy or inability to tolerate any of the agents employed
• Active, uncontrolled infection
• Severe cardiac comorbidity
• New York Heart Association Class III or IV Heart Failure
• Recent history of myocardial infarction in the six months prior to registration
• Uncontrolled angina or electrocardiographic evidence of acute ischemia
• Severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of active conduction system abnormalities
• Cardiac amyloidosis with hypotension (systolic BP less than 100 mmHg)
• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425-6350, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Cyclophosphamide; Thalidomide; Dexamethasone; Calcium Dobesilate

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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Joseph Riad Mikhael, M.D.
• Organization: Mayo Clinic

Mikhael.Joseph@mayo.edu

Study Officials

• Joseph R. Mikhael, M.D.

  Mayo Clinic

  STUDY CHAIR

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: January 26, 2010
• First Posted: January 27, 2010
• Study Start: March 1, 2010
• Primary Completion: March 1, 2014
• Study Completion: September 5, 2017
• Last Updated: December 12, 2017
• Results First Posted: September 23, 2016

Record last verified: 2017-11

Locations

US (3)