Tivantinib in Treating Patients With Relapsed, or Relapsed and Refractory Multiple Myeloma

NCT01447914 | Completed Phase 2 Results

• 7 other identifiers: NCI-2011-03470CDR00007129842011-01978984U01CA062461P30CA016672N01CM00039
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the side effects and how well tivantinib works in treating patients with relapsed, or relapsed and refractory multiple myeloma. Tivantinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Refractory Multiple Myeloma

Keywords

c-Met Inhibitor ARQ-197; tivantinib; multiple myeloma; plasma cell proliferative disorder; Hypercalcemia; hematologic malignancy; plasma cell dyscrasia; cast nephropathy; amyloidosis; osteolysis; Renal insufficiency; Anemia; Bone lytic lesions; severe osteopenia; pathologic fractures; biopsy-proven plasmacytoma

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR)

  ORR using International Myeloma Working Group Response Criteria, achieve at least a partial response (PR) or better: Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR): CR: Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow; sCR: CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; PR: ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90%; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100mg per 24 hour; Stable Disease (SD): Not CR, VGPR, PR or progressive disease; Progressive Disease (PD):\>25% from lowest value Serum and/or Urine M-component, new lesions or soft tissue plasmacytomas, or hypercalcemia.

  Up to 30 days

• Toxicities of Single Agent Tivantinib: Grade 3 Nonhematologic or Grade 4 Hematologic Toxicities According to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4

  Toxicities with a grade 3 nonhematologic or grade 4 hematologic toxicities according to CTCAE, version 4. Grade 3 and estimated with a 95% credible interval. Summary statistics will be provided for continuous variables.

  Up to 30 days

Secondary Outcomes (1)

• Time to Next Treatment (TTNT)

  From registration on trial to next treatment or death due to any cause, whichever comes first

Other Outcomes (2)

• Duration of Response

  From first observation of partial response to the time of disease progression, assessed up to 30 days

• Progression-free Survival (PFS)

  From start of the treatment to disease progression or death (regardless of cause of death), whichever comes first, assessed up to 30 days

Study Arms (1)

ARQ 197 Treatment (Tivantinib)

EXPERIMENTAL

Oral Tivantinib 360 mg twice daily continuously for each day (days 1-28) of every 4-week treatment cycle (taken as three tablets of 120 mg each). Courses continue every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Tivantinib; Other: Diagnostic laboratory biomarker analysis; Other: Questionnaire administration; Procedure: Quality-of-life assessment

Interventions

Tivantinib DRUG

Given at a dose of 360 mg oral (PO) twice daily continuously for each day of every 4-week treatment cycle, which will be taken as three tablets of 120 mg each.

Also known as: ARQ 197, c-Met Inhibitor ARQ 197

ARQ 197 Treatment (Tivantinib)

Diagnostic laboratory biomarker analysis OTHER

Correlative studies

ARQ 197 Treatment (Tivantinib)

Questionnaire administration OTHER

Ancillary studies

ARQ 197 Treatment (Tivantinib)

Quality-of-life assessment PROCEDURE

Ancillary studies

Also known as: quality of life assessment

ARQ 197 Treatment (Tivantinib)

Eligibility Criteria

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

You may qualify if:

• Patients must have been previously diagnosed with histologically or cytologically confirmed symptomatic multiple myeloma, which requires the presence of all three of the following International Myeloma Working Group criteria, except as noted:
• Clonal bone marrow plasma cells \>= 10%
• A monoclonal protein in either serum or urine
• Evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder (to include one of the following):
• Hypercalcemia (corrected calcium \> 2.75 mmol/L or 11.5 mg/dL)
• Renal insufficiency attributable to myeloma (serum creatinine \> 1.9 mg/dL)
• Anemia; normochromic, normocytic with a hemoglobin value \>= 2 g/dL below the lower limit of normal, or a hemoglobin or \< 10 g/dL
• Bone lytic lesions, severe osteopenia, or pathologic fractures
• Patients with a biopsy-proven plasmacytoma and either a serum or urine monoclonal protein will also be considered to have met the diagnostic criteria for multiple myeloma in the absence of clonal marrow plasmacytosis of \>= 10%
• Patients must have measurable disease, as defined by at least one of the following:
• Serum monoclonal protein level \>= 0.5 g/dL for immunoglobulin (Ig)G, IgA, or IgM disease
• Monoclonal protein or total serum IgD \>= 0.5 g/dL for IgD disease
• Urinary M-protein excretion of \>= 200 mg over a 24-hour period
• Involved free light chain level \>= 10 mg/dL, along with an abnormal free light chain ratio
• Patients must have had at least one, but not more than four prior lines of therapy for their disease, with lines of therapy being separated by the presence of documented disease progression; using this definition, treatment with induction therapy, followed by high-dose chemotherapy and autologous stem cell transplantation, and finally by maintenance therapy, would constitute one line, provided that multiple myeloma did not meet criteria for progression at any time during this period

You may not qualify if:

• Patients who are receiving any concurrent investigational agent with known or suspected activity against multiple myeloma, or those whose adverse events due to agents administered more than 4 weeks earlier have not recovered to a severity of grade 0 or grade 1
• Patients who have known central nervous system involvement with multiple myeloma will be excluded from this clinical trial
• Patients who have previously been treated with another agent targeting the HGF/c-Met axis, including either monoclonal antibodies to HGF or c-Met, or small molecule inhibitors of c-Met
• Patients with a known history of allergic reactions attributed to compounds of similar chemical or biologic composition to ARQ 197
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, in the opinion of the Principal Investigator
• Pregnant or lactating women are excluded from this study
• HIV positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ARQ 197; however, HIV seropositive patients with acceptable organ function who meet the patient selection criteria, and who are not on combination antiretroviral therapy, will be eligible
• Patients with non-secretory multiple myeloma, active plasma cell leukemia, defined as either having 20% of peripheral white blood cells comprised of CD138+ plasma cells, or an absolute plasma cell count of 2 x 10\^9/L, known amyloidosis, or known POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Patients who have required plasmapheresis and exchange less than 2 weeks prior to initiation of therapy with ARQ 197
• Patients with known active hepatitis A, B, and/or C infection
• Patients with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled; patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for \> 5 years, and are considered by their physician to be at less than 30% risk of relapse; in addition, patients with basal cell carcinoma of the skin, superficial carcinoma of the bladder, carcinoma of the prostate with a current prostate-specific antigen (PSA) value of \< 0.5 ng/mL, or cervical intraepithelial neoplasia will be eligible; finally, patients who are on hormonal therapy for a history of either prostate cancer or breast cancer may enroll, provided that there has been no evidence of disease progression during the previous three years

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Official Website

MeSH Terms

Conditions

Multiple Myeloma; Hypercalcemia; Hematologic Neoplasms; Paraproteinemias; Amyloidosis; Osteolysis; Renal Insufficiency; Anemia; Bone Diseases, Metabolic; Fractures, Spontaneous

Interventions

ARQ 197

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Water-Electrolyte Imbalance; Neoplasms by Site; Proteostasis Deficiencies; Bone Resorption; Bone Diseases; Musculoskeletal Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Fractures, Bone; Wounds and Injuries

Results Point of Contact

• Title: Robert Orlowski, MD, PhD / Professor, Department of Lymphoma/Myeloma
• Organization: University of Texas (UT) MD Anderson Cancer Center

ROrlowski@mdanderson.org

713-792-2860

Study Officials

• Robert Orlowski

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2011
• First Posted: October 6, 2011
• Study Start: November 1, 2011
• Primary Completion: March 1, 2014
• Study Completion: April 1, 2014
• Last Updated: August 28, 2019
• Results First Posted: March 13, 2015

Record last verified: 2019-08

Locations

US (1)