Carfilzomib and Stem Cell Transplant for Plasma Cell Myeloma

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01658904
First received: August 3, 2012
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

Background:

- Plasma cell myeloma is a type of cancer that affects the plasma cells in the bone marrow. It can be difficult to treat with chemotherapy. One possible treatment combines chemotherapy with a stem cell transplant. To make this treatment more effective, researchers want to give another drug along with the transplant. This drug, carfilzomib, is often used to help treat plasma cell myeloma. However, it is not usually given along with the transplant. Researchers want to see if it is safe and effective to combine the stem cell transplant with carfilzomib, and if it improves the results of the transplant.

Objectives:

- To test the safety and effectiveness of carfilzomib given with stem cell transplant for plasma cell myeloma.

Eligibility:

- Individuals between 18 and 75 years of age who are having a stem cell transplant to treat plasma cell myeloma.

Design:

  • Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies and a bone marrow biopsy will also be performed.
  • Participants will have their own stem cells collected for the transplant. The transplant will be performed according to the standard of care.
  • All participants will receive carfilzomib on the first 2 days after transplant. The study doctors will determine the number of additional doses that they may have.
  • Treatment will be monitored with frequent blood tests and imaging studies.

Condition Intervention Phase
Multiple Myeloma
Leukemia, Plasma Cell
Drug: Carfilzomib
Drug: Melphalan
Drug: Filgrastim
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I / II Study Of Carfilzomib (CFZ) Intensification Early After Autologous Transplantation (AHCT) For Plasma Cell Myeloma

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Engraftment failure transplant related mortality

Secondary Outcome Measures:
  • Response rate at day 100 post-AHCT

Enrollment: 3
Study Start Date: July 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Carfilzomib
    N/A
    Drug: Melphalan
    N/A
    Drug: Filgrastim
    N/A
Detailed Description:

Background:

  • Despite very significant progress in therapy for plasma cell myeloma (PCM) in the last decade, the disease remains mostly incurable.
  • High-dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT) continues to be a critical component of early treatment for PCM, but it is clear that the disease is not eradicated by the present high-dose therapy strategy, while intensifying the preparative regimen has, to this day, resulted in either no improvement in disease control or increased toxicity.
  • Carfilzomib (CFZ) is a newer proteasome inhibitor with increased activity and a safer toxicity profile than bortezomib in PCM. The favorable toxicity profile makes it a likely candidate for increasing anti-PCM drug exposure in the early post-AHCT period.

Objectives:

Primary Objectives

-Evaluate feasibility and toxicity of an increasing number of doses of CFZ administered in the early period post-AHCT for PCM

Secondary Objective

  • Evaluate the immune reconstitution post-AHCT following CFZ therapy
  • Evaluate the effects of the addition of CFZ in the early post-AHCT period on the response rate at day 100 post-AHCT

Eligibility:

  • Newly diagnosed subjects with PCM following induction therapy
  • Subjects with documentation of persistent/refractory disease who have received no more than 2 salvage regimens following relapse and who have not undergone AHCT
  • Adequate organ functions with no major co-morbidity
  • Age greater than 18 years and less than or equal to 75 years

Design:

  • Phase I/II study on the backbone of high-dose melphalan on day -2 pre-AHCT
  • Addition of an increasing number of doses of CFZ in the early post-AHCT period introduced in a step-wise fashion in 3 successive cohorts of 3 to 15 subjects:

Cohort 1: add CFZ 20 mg/m2 on days +1, +2

Cohort 2 : add CFZ 20 mg/m2 on days: +1, +2, +8, +9

Cohort 3: add CFZ 20 mg/m2 on days: +1, +2, +8, +9 and add an early post-AHCT consolidation following

engraftment: CFZ 20 mg/m2 given on days 42-43 then CFZ 56 mg/m2 given on days 49-50, 56-57, then on days 70-71, 77-78 and 84-85

-Dose-limiting toxicity, incidence of engraftment failure and treatment-related mortality are the objects of early stopping rules for safety purposes

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Multiple myeloma criteria for newly or recently diagnosed subjects

  • Presence of clonal plasma cells in the bone marrow greater than or equal to 10% or a documented clonal plasmacytoma (either by immuno-histochemistry or by Ig gene rearrangement), AND
  • Presence of an M-component; an M-component (IgG or IgA) in serum greater than or equal to 1g/dl or in urine greater or equal to 200 mg/24 h.

ALTERNATIVELY, if the M-component criterion is not met:

  • An abnormal serum free light chain (FLC) ratio on the serum FLC assay, or if the FLC ratio is normal,
  • Baseline bone marrow must have 10% or greater clonal plasma cells

AND, IN ADDITION, presence of one or more of the following attributable to the disease (in the presence or absence of an M-component):

  • Calcium elevation greater than 11.5 mg/dl (2.65 mmol/l)
  • Renal insufficiency: serum creatinine greater than 2 mg/dl (177 mmol/l) or less than 60ml/min.
  • Hemoglobin less than 10 g/dl (12.5 mmol/l) or 2 g/dl (1.25 mmol/l) below lower normal
  • Bone disease (lytic lesions or osteopenia)
  • Other evidence of disease activity: repeated infections, secondary amyloidosis, hyperviscosity, hypogammablobulinemia

Criteria for subjects with persistent or recurrent disease

Subjects with recurrent or persistent disease are eligible if:

  • Criteria for initiating therapy for PCM had been present at the time of initiation of therapy or there is clear clinical indication for salvage therapy.
  • They have not undergone an autologous transplant for the treatment of PCM
  • They have received no more than two salvage regimens for the treatment of recurrent or persistent PCM (each regimen may include more than one cycle)

Other eligibility criteria

-Age > 18 years and less than or equal to 75 years.

In subjects between 65 and 75 years of age, physiologic age and co-morbidity will be thoroughly evaluated before enrolling. Specifically, any history of cardiovascular pathology or symptoms not clearly fitting the exclusion criteria of Section 2.1.2 will prompt an evaluation by a Clinical Center Cardiologist and eligibility will be considered on a case-by-case basis.

  • Karnofsky performance status of 70% or greater (ECOG 0 or 1)
  • Ejection fraction (EF) by MUGA or 2-D echocardiogram within institution normal limits. In case of low EF, the subject may remain eligible after a stress echocardiogram is performed if the EF is more than 35% and if the increase in EF with stress is estimated at 10% or more.
  • creatinine clearance > 25ml/min (measured on a 24 hour urine collection)
  • AST and ALT less than or equal to 3 x upper limit of normal
  • Bilirubin less than or equal to1.5 (except if due to Gilbert's disease)
  • Corrected DLCO greater than or equal to 40% on pulmonary function tests

EXCLUSION CRITERIA:

  • Prior allogeneic or autologous stem cell transplantation
  • Prior treatment with CFZ is not an exclusion
  • History of recent (< 6 months) cerebrovascular accident
  • History of documented recent (< 6 months) pulmonary embolus
  • Clinically significant cardiac pathology:
  • Myocardial infarction within 6 months prior to enrollment,
  • Class III or IV heart failure according to NYHA,
  • Uncontrolled angina,
  • Severe uncontrolled ventricular arrhythmias, or
  • Electrocardiographic evidence of acute ischemia or active conduction abnormalities felt to pose a significant cardiac riks by a Cardiology consultant
  • Patients with a history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis.
  • HIV seropositive
  • Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrollment
  • Active hepatitis B or C infection
  • Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment
  • Major surgery within 21 days prior to enrollment
  • Non-hematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
  • Significant neuropathy (Grades 3 4, or Grade 2 with pain) within 14 days prior to randomization
  • Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize CFZ)
  • Patients known or found to be pregnant
  • Female patients of childbearing age who are unwilling to practice contraception
  • Patients may be excluded at the discretion of the PI if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk.
  • Patients must be able to give informed consent
  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: NCT01658904

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Ronald E Gress, M.D. National Cancer Institute (NCI)
  More Information

Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01658904     History of Changes
Other Study ID Numbers: 120179, 12-C-0179
Study First Received: August 3, 2012
Last Updated: May 28, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Autologous Transplant
Proteasome Inhibitor
Melphalan
Filgrastim

Additional relevant MeSH terms:
Leukemia, Plasma Cell
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Leukemia
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Lenograstim
Melphalan
Adjuvants, Immunologic
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014