Trial record 1 of 1 for:    NCT 01903811
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S1304, Testing Two Doses of Carfilzomib With Dexamethasone for Relapsed or Refractory Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Southwest Oncology Group
Sponsor:
Collaborators:
Onyx Pharmaceuticals
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT01903811
First received: July 16, 2013
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

This randomized phase II trial studies how well two doses of carfilzomib work with dexamethasone in treating patients with relapsed or refractory multiple myeloma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving carfilzomib together with dexamethasone may kill more cancer cells. This study is looking to see if giving a higher or lower dose of carfilzomib with dexamethasone is more beneficial than the other.


Condition Intervention Phase
Relapsed or Refractory Multiple Myeloma
Drug: dexamethasone
Drug: carfilzomib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: S1304, A Phase II Randomized Study Comparing Two Doses of Carfilzomib (NSC-756640) With Dexamethasone for Multiple Myeloma Patients With Relapsed or Refractory Disease

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    Assessed in each arm using the method of Kaplan Meier and compared between arms using the stratified long-rank test.


Secondary Outcome Measures:
  • Response rate (stringent complete response [sCR], complete response [CR], very good partial response [VGPR], partial response [PR]) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Assessed in each arm and compared between arms using Fisher's exact test.

  • Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Assessed in each arm using the method of Kaplan Meier and compared between arms using the stratified log-rank test.


Estimated Enrollment: 140
Study Start Date: September 2013
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (dexamethasone, low-dose carfilzomib)
Patients receive dexamethasone IV and low-dose carfilzomib IV over 2-10 minutes on days 1, 2, 8, 9, 15, and 16. (Note that cycle 1 is given at a reduced dose.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients with progression cross-over to Arm II.
Drug: dexamethasone
given IV
Other Name: decadron
Drug: carfilzomib
given IV
Other Names:
  • kyprolis
  • PR-171
Experimental: Arm II (dexamethasone, high-dose carfilzomib)
Patients receive dexamethasone IV and high-dose carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16. (Note that cycle 1 is given at a reduced dose over 2-10 minutes.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Drug: dexamethasone
given IV
Other Name: decadron
Drug: carfilzomib
given IV
Other Names:
  • kyprolis
  • PR-171

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate and compare progression free survival (PFS) of two different doses of carfilzomib with dexamethasone in multiple myeloma (MM) patients with relapsed and/or refractory disease.

SECONDARY OBJECTIVES:

I. To evaluate and compare response rates (RR) for each arm. II. To evaluate response rates (RR) for patients that relapse on low dose carfilzomib and subsequently cross-over to high dose carfilzomib.

III. To evaluate the safety of this combination for this patient population. IV. To evaluate overall survival (OS).

TERTIARY OBJECTIVES:

I. To explore the molecular variability in MM cells obtained from extramedullary bone marrow relapse sites.

II. To explore the role of positron emission tomography (PET) scanning in assessing disease burden and as a tool to assess treatment response.

III. To explore changes in left ventricular ejection fraction (LVEF) in patients with relapsed or refractory multiple myeloma treated with low dose carfilzomib or high dose carfilzomib plus dexamethasone.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive dexamethasone intravenously (IV) and low-dose carfilzomib IV over 2-10 minutes on days 1, 2, 8, 9, 15, and 16. Patients with progression cross-over to Arm II.

ARM II: Patients receive dexamethasone IV and high-dose carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16.

Note that for the first course of treatment on both arms carfilzomib is given at a reduced rate to assess toxicity.

In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years from initial registration.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • REGISTRATION STEP 1: INITIAL RANDOMIZATION
  • Patients must have a confirmed diagnosis of symptomatic multiple myeloma and must be relapsed or refractory; all tests for establishing disease status must be completed within 28 days prior to registration and documented on the Baseline Tumor Assessment Form for Multiple Myeloma
  • Patients must have measurable disease within 28 days prior to registration
  • Patients must have received at least one prior regimen of chemotherapy for symptomatic multiple myeloma; patients may not have more than six (6) previous regimens of therapy for the disease; prior chemotherapy must have been completed at least 28 days prior to registration; for study purposes, a regimen is defined as follows:

    • An anti-myeloma therapy used at the time of initial diagnosis or documented disease progression which is given with the intent to decrease disease burden
    • Any maintenance therapy used after an Induction should be considered part of that Induction regimen
    • Use of any agent or combination of agents more than once during the patient's disease history for separate documented disease progressions will be counted as separate regimens (e.g., if a patient receives lenalidomide/bortezomib at initial diagnosis and achieves response, but then progresses and receives lenalidomide/bortezomib after progression, these count as 2 separate regimens)
    • In cases of autologous stem cell transplant, the entire induction + stem cell mobilization + conditioning + planned maintenance should be considered one regimen
  • Patients may not have received any prior carfilzomib treatment
  • Patients must not be receiving any other concurrent therapy considered to be investigational; patients must not be planning to receive any radiotherapy (except localized radiation for palliative care); patients must not be planning to receive any concurrent chemotherapy, immunotherapy, radiotherapy or other treatment with curative intent
  • Patients must have complete history and physical examination within 28 days prior to registration
  • Patients must have baseline PET scan within 28 days prior to registration; note that images are submitted centrally for review
  • Patients with non-secretory MM or known primary amyloidosis are not eligible
  • Patients must have Zubrod performance status 0-2
  • Patients must not have clinically significant illness including uncontrolled, active infection requiring intravenous antibiotics, New York Heart Association (NYHA) class III or class IV heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or >= grade 3 cardiac arrhythmias
  • Patients must have undergone an electrocardiogram (EKG) within 28 days prior to registration
  • Patients must have either echocardiogram (ECHO) with ejection fraction >= 45% within 28 days prior to registration
  • Patients must not have > grade 2 neuropathy and/or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 3 x ULN
  • Absolute neutrophil count (ANC) >= 1,000 cell/mm^3 without growth factor support within 14 days prior to registration
  • Platelets >= 50,000 cells/mm^3 for patients who have bone marrow plasmacytosis < 50% or >= 30,000 cells/mm^3 for patients who have bone marrow plasmacytosis of >= 50% within 14 days prior to registration
  • Calculated or measured creatinine clearance >= 30 ml/min within 14 days prior to registration
  • Patients who are known to be human immunodeficiency virus positive (HIV+) are eligible providing they meet all of the following additional criteria within 28 days prior to registration:

    • Cluster of differentiation (CD)4 cells >= 500/mm^3
    • Viral load of < 50 copies HIV messenger ribonucleic acid (mRNA)/mm^3 if on combination antiretroviral therapy (cART) or < 25,000 copies HIV mRNA if not on cART
    • No zidovudine or stavudine as part of cART
    • Patients who are HIV+ and do not meet all of these criteria are not eligible for this study
  • Patients with known hepatitis B or hepatitis C infection must have viral load < 800,000 IU/L within 28 days prior to registration
  • Patients must have baseline skeletal survey to document lytic lesions, osteopenia or compression fracture within 28 days prior to registration
  • Patients must be off myelosuppressive chemotherapy and non-myelosuppressive chemotherapy and external beam radiation therapy (XRT) for >= 28 days (>= 6 weeks for nitrosoureas) and must have recovered to =< grade 1 from all treatment associated toxicities prior to registration; patients are allowed to have treatment for up to 7 days with pulse steroids for a myeloma-related complication prior to registration, as considered necessary by the treating physician
  • Patients must be offered participation in specimen submission for translational medicine studies and banking; with patient consent, specimens must be submitted
  • Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years
  • Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  • REGISTRATION STEP 2: CROSSOVER
  • Patient must have been eligible for and initially randomized to Arm 1 (low dose carfilzomib) and progressed prior to completing 12 cycles of protocol therapy
  • At least 14 days and no more than 28 days must have elapsed between the last day of treatment on Arm 1 and registration to Arm 3
  • Patients must have recovered from all non-hematologic toxicities to =< grade 2 and from all hematologic toxicities to =< grade 3 prior to registration
  • Patients must have been able to complete their last treatment cycle prior to progression at the full assigned dose (i.e. no dose reduction for toxicity)
  • Patients must have serum protein electrophoresis (SPEP) and kappa and lambda light chain testing performed within 14 days prior to registration in order to establish baseline measurements
  • Patients must not have ejection fraction decrease > 10% from baseline (as determined by ECHO) or other ejection fraction decrease accompanied by other clinical signs/symptoms of New York Heart Association (NYHA) class III or IV heart failure, measured within 28 days prior to registration; if any question exists regarding individual patient eligibility in this situation, contact the study coordinator for determination
  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 ClinicalTrials.gov identifier: NCT01903811

Contacts
Contact: Sandi J Fredette 210/614-8808 sfredette@swog.org
Contact: Dana B Sparks, MAT 210/614-8808 dsparks@swog.org

  Show 171 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Onyx Pharmaceuticals
Investigators
Study Chair: Sikander Ailawadhi, MD Southwest Oncology Group
Study Chair: Muneer Abidi, MD` Southwest Oncology Group
  More Information

No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT01903811     History of Changes
Other Study ID Numbers: S1304, U10CA032102, NCI-2013-00796, S1304
Study First Received: July 16, 2013
Last Updated: April 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:
carfilzomib
relapsed, refractory, multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 22, 2014