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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Stanford University
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Michaela Liedtke, Stanford University Identifier:
First received: April 29, 2010
Last updated: November 10, 2013
Last verified: November 2013

This is an open-label Phase I dose-escalation safety study of VELCADE in combination with pralatrexate in patients with previously treated multiple myeloma. In a standard 3+3 dose escalation trial design, escalating doses of pralatrexate in combination with VELCADE will be studied sequentially, with at least 3 patients in each dose level until the MTD is determined. Dose limiting toxicity (DLT) and MTD are determined during cycle 1 of treatment.

Condition Intervention Phase
Multiple Myeloma
Drug: velcade
Drug: Pralatrexate
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Bortezomib (VELCADE) in Combination With Pralatrexate in Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:

Further study details as provided by Stanford University:

Primary Outcome Measures:
  • The maximum tolerated dose (MTD) for the combination of pralatrexate with VELCADE in previously treated adult patients with multiple myeloma. [ Time Frame: assessed upon completion of cycle 1 of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical evidence of anti-tumor activity based on response rates [ Time Frame: assessed after each 4 week cycle (up to 4 cycles) ] [ Designated as safety issue: No ]
  • Time to progression (TTP) [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Duration of Response Outcome [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Progression free survival (PFS) [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 28
Study Start Date: August 2010
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VELCADE with pralatrexate
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


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

Inclusion Criteria:

  • 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:

    1. serum M-protein >=1 g/dL
    2. 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.
  • No poorly controlled intercurrent illness including, but not limited to, ongoing or active infection, poorly controlled diabetes, symptomatic congestive heart failure, or psychiatric illness that in the opinion of the investigator would limit compliance with study requirements.
  • Patients must have adequate bone marrow function: Platelets >100 x 109/L, Hemoglobin > 8.0g/dL and ANC > 1 x 109/L
  • Patients must have adequate liver functions: AST and ALT < 2.5 X upper limit of normal, Total bilirubin <= 1.5 x ULN
  • Patients must have adequate renal function defined as creatinine clearance of 30 ml/minute (Cockcroft-Gault).
  • The patient must have been on a regimen of 1.0 - 1.25 mg PO QD of folic acid for at least 10 days prior to the planned start of pralatrexate and received 1 mg IM of vitamin B12 within 10 weeks of the planned start of pralatrexate.
  • Patients with reproductive potential must use an effective method of contraception to avoid pregnancy for the duration of the trial.
  • If female of childbearing potential, pregnancy test must be negative within 7 days prior to registration for protocol therapy.
  • Ability to understand and the willingness to sign a written informed consent document including HIPAA authorization for release of personal health information.
  • The patient must be willing and able to receive outpatient treatment and laboratory monitoring at the Stanford Cancer Center.

Exclusion Criteria:

  • 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.
  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 identifier: NCT01114282

Contact: Vani Jain (650) 725-5459

United States, California
Stanford University School of Medicine Recruiting
Stanford, California, United States, 94305
Contact: Vani Jain    650-725-5459   
Contact: Cancer Clinical Trials Office    (650) 498-7061      
Principal Investigator: Michaela Liedtke         
Sub-Investigator: Bruno Carneiro de Medeiros         
Sub-Investigator: Steven Edward Coutre         
Sub-Investigator: Jason Robert Gotlib         
Sponsors and Collaborators
Michaela Liedtke
National Comprehensive Cancer Network
Principal Investigator: Michaela Liedtke Stanford University
  More Information

No publications provided

Responsible Party: Michaela Liedtke, Assistant Professor of Medicine (Hematology), Stanford University Identifier: NCT01114282     History of Changes
Other Study ID Numbers: HEMMYL0014, SU-04282010-5783
Study First Received: April 29, 2010
Last Updated: November 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists processed this record on July 20, 2014