Phase I Bortezomib (VELCADE) in Combo With Pralatrexate in Relapsed/Refractory MM

NCT01114282 | Completed Phase 1

• 2 other identifiers: HEMMYL0014SU-04282010-5783
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this trial is to find out the maximum tolerated dose (MTD) of bortezomib (VELCADE) in combination with pralatrexate in patients with previously treated multiple myeloma, AL amyloid and Waldenstroem's macroglobulinemia.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• The maximum tolerated dose (MTD) for the combination of pralatrexate with VELCADE in previously treated adult patients with multiple myeloma.

  assessed upon completion of cycle 1 of treatment

Secondary Outcomes (5)

• Clinical evidence of anti-tumor activity based on response rates

  assessed after each 4 week cycle (up to 4 cycles)

• Time to progression (TTP)

  assessed after each 4 week cycle (up to 4 cycles) and every 3 months for the first 2 years from protocol registration, every 6 months for years 3-5 and annually thereafter

• Duration of Response Outcome

  assessed after each 4 week cycle (up to 4 cycles) and every 3 months for the first 2 years from protocol registration, every 6 months for years 3-5 and annually thereafter

• Progression free survival (PFS)

  assessed after each 4 week cycle (up to 4 cycles) and every 3 months for the first 2 years from protocol registration, every 6 months for years 3-5 and annually thereafter

• Overall survival (OS)

  assessed after each 4 week cycle (up to 4 cycles) and every 3 months for the first 2 years from protocol registration, every 6 months for years 3-5 and annually thereafter

Study Arms (1)

VELCADE with pralatrexate

EXPERIMENTAL

Pralatrexate,10 mg/m2, IV bolus on days 1, 8, and 15 VELCADE,1.3 mg/m2, IV bolus on days 1, 8, and 15

Drug: velcade; Drug: Pralatrexate

Interventions

velcade DRUG

VELCADE with pralatrexate

Pralatrexate DRUG

VELCADE with pralatrexate

Eligibility Criteria

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

You may qualify if:

• The patient has relapsed or refractory multiple myeloma that has progressed following at least on prior therapy.
• Relapsed myeloma is defined in patients as at least 25% increasing monoclonal (M)-protein in serum or urine or in the size of a plasmacytoma compared to a best response reached after previous therapy.
• Refractory myeloma is defined as failure to achieve at least a minor response (patient achieved stable disease as his/her best response) or progression of disease on current therapy or within 60 days of last dose of current therapy.
• The patient has measurable disease defined as one of the following:
• serum M-protein \>=1 g/dL
• urine M-protein \>=200 mg/24 hours
• Must have received at least one (1) prior line of systemic treatment that may have included VELCADE.
• a. NOTE: Patients may have undergone prior allogeneic or autologous stem cell transplantation (stem cell transplant with high dose induction chemotherapy with/without planned maintenance therapy will be considered one line of therapy).
• No cytotoxic chemotherapy within 4 weeks prior to registration for protocol therapy.
• a. NOTE: this interval may be reduced to 14 days for thalidomide, lenalidomide, VELCADE or corticosteroids, provided other entry criteria are met.
• No concurrent steroid use in doses greater than 10 mg daily of Prednisone (or equivalent) if given for management of co-morbid conditions.
• Age \>= 18 at the time of consent.
• The patient has a life expectancy of more than 3 months.
• No known central nervous system involvement by myeloma.
• ECOG performance status 0-2.

You may not qualify if:

• The patient has nonmeasurable multiple myeloma, defined as less than 1g/dl M-protein in serum and less than 200 mg/24 hours M-protein in urine.
• The patient received glucocorticoid therapy (prednisone \> 10 mg/day orally or equivalent) within the last 2 weeks prior to the first dose of study drug.
• The patient received chemotherapy with approved or investigative anticancer therapeutics within 4 weeks.
• a. NOTE: this interval may be reduced to 14 days for thalidomide, lenalidomide, VELCADE or corticosteroids, provided other entry criteria are met.
• The patient has an acute infection requiring systemic antibiotics, antiviral agents, or antifungal agents within 2 weeks before the first dose of study drug.
• The patient has grade 2 or higher neuropathy within 14 days of enrollment.
• The patient has any serious psychiatric or medical condition that could interfere with treatment and study procedures, place the patient at unacceptable risk, or confound the ability of investigators to interpret study data.
• The patient is a pregnant or lactating woman.
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see Appendix A), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the Investigator as not medically relevant.
• Patient has hypersensitivity to VELCADE, boron or mannitol.
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

Sponsors & Collaborators

• Stanford University: lead
• National Comprehensive Cancer Network: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (1)

• Dunn TJ, Dinner S, Price E, Coutre SE, Gotlib J, Hao Y, Berube C, Medeiros BC, Liedtke M. A phase 1, open-label, dose-escalation study of pralatrexate in combination with bortezomib in patients with relapsed/refractory multiple myeloma. Br J Haematol. 2016 Apr;173(2):253-9. doi: 10.1111/bjh.13946. Epub 2016 Apr 4.

  PMID: 27040320 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; 10-propargyl-10-deazaaminopterin

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

• Michaela Liedtke

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine (Hematology)

Study Record Dates

• First Submitted: April 29, 2010
• First Posted: May 3, 2010
• Study Start: August 1, 2010
• Primary Completion: February 1, 2014
• Last Updated: July 6, 2016

Record last verified: 2016-07

Locations

US (1)