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Carfilzomib Based Chemotherapy Mobilization for Autologous Stem Cell Transplants in Multiple Myeloma (CarMob)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03909412
Recruitment Status : Recruiting
First Posted : April 10, 2019
Last Update Posted : September 16, 2020
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Hackensack Meridian Health

Brief Summary:
This phase I study utilizes a 3+3 design with escalating cohorts of Carfilzomib at 20mg/m2, 27mg/m2, 36mg/m2, 45mg/m2, 56mg/m2, and 70mg/m2 to be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone and G-CSF

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Carfilzomib Drug: Cyclophosphamide Drug: Dexamethasone Drug: Granulocyte Colony-Stimulating Factor Phase 1

Detailed Description:

This study will be conducted as an open-label Phase I, single-center study in which subjects will receive carfilzomib, in combination cyclophosphamide and dexamethasone, for mobilization of peripheral blood stem cells. Study treatment will be administered in sequential cohorts, with three to six subjects in each cohort.

Following induction therapy, eligible patients will complete screening procedures. Treatment will consist of Dexamethasone 40mg IV/PO to be administered as a premedication. Carfilzomib dosed at each respective cohort level to be administered over 30 minutes followed by Cyclophosphamide dosed at 2gm/m2 administered over 1 hour.

For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.

On day 7 subjects will initiate high dose G-CSF injections at 14mcg/kg daily (with a cap of 1440mcg daily). On day 12 peripheral blood stem cell collection will begin per institutional protocol.

After successful peripheral blood stem cell mobilization, patients will proceed to a melphalan based autologous stem cell transplant.

Patients will have disease parameters assessed monthly after the transplant.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: This phase I study utilizes a 3+3 design with escalating cohorts of Carfilzomib at 20mg/m2, 27mg/m2, 36mg/m2, 45mg/m2, 56mg/m2, and 70mg/m2 to be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone and G-CSF
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Carfilzomib-based Chemotherapy Mobilization for Autologous Stem Cell Transplantation in Multiple Myeloma
Actual Study Start Date : October 8, 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Carfilzomib

Arm Intervention/treatment
Experimental: Carfilzomib Mobilization - Dose Level 0

Carfilzomib at 20mg/m2 over 10 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.

For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.

Drug: Carfilzomib
Carfilzomib will be administered over 10 minutes for the 20 mg/m2 and 27 mg/m2 dose and over 30 minutes for all higher doses.
Other Name: Kyprolis

Drug: Cyclophosphamide
Cyclophosphamide dosed at 2gm/m2 administered over 1 hour.
Other Name: Cytoxan

Drug: Dexamethasone
Dexamethasone 40mg IV/PO to be administered as a premedication.
Other Name: Decadron

Drug: Granulocyte Colony-Stimulating Factor
On day 7 subjects will initiate high dose G-CSF injections at 14mcg/kg daily (with a cap of 1440mcg daily).
Other Names:
  • G-CSF
  • Filgrastim
  • Neupogen

Experimental: Carfilzomib Mobilization - Dose Level 1

Carfilzomib at 27mg/m2 over 10 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.

For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.

Drug: Carfilzomib
Carfilzomib will be administered over 10 minutes for the 20 mg/m2 and 27 mg/m2 dose and over 30 minutes for all higher doses.
Other Name: Kyprolis

Drug: Cyclophosphamide
Cyclophosphamide dosed at 2gm/m2 administered over 1 hour.
Other Name: Cytoxan

Drug: Dexamethasone
Dexamethasone 40mg IV/PO to be administered as a premedication.
Other Name: Decadron

Drug: Granulocyte Colony-Stimulating Factor
On day 7 subjects will initiate high dose G-CSF injections at 14mcg/kg daily (with a cap of 1440mcg daily).
Other Names:
  • G-CSF
  • Filgrastim
  • Neupogen

Experimental: Carfilzomib Mobilization - Dose Level 2

Carfilzomib at 36mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.

For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.

Drug: Carfilzomib
Carfilzomib will be administered over 10 minutes for the 20 mg/m2 and 27 mg/m2 dose and over 30 minutes for all higher doses.
Other Name: Kyprolis

Drug: Cyclophosphamide
Cyclophosphamide dosed at 2gm/m2 administered over 1 hour.
Other Name: Cytoxan

Drug: Dexamethasone
Dexamethasone 40mg IV/PO to be administered as a premedication.
Other Name: Decadron

Drug: Granulocyte Colony-Stimulating Factor
On day 7 subjects will initiate high dose G-CSF injections at 14mcg/kg daily (with a cap of 1440mcg daily).
Other Names:
  • G-CSF
  • Filgrastim
  • Neupogen

Experimental: Carfilzomib Mobilization - Dose Level 3

Carfilzomib at 45mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.

For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.

Drug: Carfilzomib
Carfilzomib will be administered over 10 minutes for the 20 mg/m2 and 27 mg/m2 dose and over 30 minutes for all higher doses.
Other Name: Kyprolis

Drug: Cyclophosphamide
Cyclophosphamide dosed at 2gm/m2 administered over 1 hour.
Other Name: Cytoxan

Drug: Dexamethasone
Dexamethasone 40mg IV/PO to be administered as a premedication.
Other Name: Decadron

Drug: Granulocyte Colony-Stimulating Factor
On day 7 subjects will initiate high dose G-CSF injections at 14mcg/kg daily (with a cap of 1440mcg daily).
Other Names:
  • G-CSF
  • Filgrastim
  • Neupogen

Experimental: Carfilzomib Mobilization - Dose Level 4

Carfilzomib at 56mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.

For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.

Drug: Carfilzomib
Carfilzomib will be administered over 10 minutes for the 20 mg/m2 and 27 mg/m2 dose and over 30 minutes for all higher doses.
Other Name: Kyprolis

Drug: Cyclophosphamide
Cyclophosphamide dosed at 2gm/m2 administered over 1 hour.
Other Name: Cytoxan

Drug: Dexamethasone
Dexamethasone 40mg IV/PO to be administered as a premedication.
Other Name: Decadron

Drug: Granulocyte Colony-Stimulating Factor
On day 7 subjects will initiate high dose G-CSF injections at 14mcg/kg daily (with a cap of 1440mcg daily).
Other Names:
  • G-CSF
  • Filgrastim
  • Neupogen

Experimental: Carfilzomib Mobilization - Dose Level 5

Carfilzomib at 70mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.

For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.

Drug: Carfilzomib
Carfilzomib will be administered over 10 minutes for the 20 mg/m2 and 27 mg/m2 dose and over 30 minutes for all higher doses.
Other Name: Kyprolis

Drug: Cyclophosphamide
Cyclophosphamide dosed at 2gm/m2 administered over 1 hour.
Other Name: Cytoxan

Drug: Dexamethasone
Dexamethasone 40mg IV/PO to be administered as a premedication.
Other Name: Decadron

Drug: Granulocyte Colony-Stimulating Factor
On day 7 subjects will initiate high dose G-CSF injections at 14mcg/kg daily (with a cap of 1440mcg daily).
Other Names:
  • G-CSF
  • Filgrastim
  • Neupogen




Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 24 Months ]
    Safety and tolerability will be assessed by clinical review of all relevant parameters including Adverse Events (CTCAE v4.0)

  2. Maximum tolerated dose (MTD) [ Time Frame: 28 Days ]
    To determine the maximum tolerated dose (MTD) of carfilzomib in combination with cyclophosphamide, dexamethasone and G-CSF in mobilizing and collecting peripheral blood stem cells



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA

  • Subject has voluntarily agreed to participate by giving written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. Informed Consent must be obtained prior to mobilization.
  • Subject has a confirmed diagnosis of multiple myeloma as specified by the International Myeloma Working Group criteria and must have measurable disease as defined by at least one of the following criteria:
  • Serum monoclonal protein ≥ 0.5 g/dL
  • ≥200 mg of monoclonal protein in the urine on 24-hour electrophoresis
  • Serum immunoglobulin free light chain: involved FLC ≥ 10 mg/dL (≥ 100 mg/L) AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
  • Subject is ≥18 years of age at the time of signing the informed consent form.
  • Subject has an ECOG performance status of < 2.
  • Subjects must have measurable monoclonal protein, free light chains, and/or M-spike in blood or urine.
  • Subjects must have completed any "induction therapy"and have achieved less than a CR.
  • Subject has a life expectancy of >12 weeks.

    • Absolute neutrophil count (ANC) ≥1000 cells/mm3 (≥500 for patients with bone marrow biopsy displaying >50% involvement by myeloma)
    • Platelets count ≥ 50,000/mm3 (≥ 30,000 for patients with bone marrow biopsy displaying >50% involvement by myeloma)
    • Hemoglobin > 9.0 g/dL
    • Serum SGOT/AST <3.0 x upper limits of normal (ULN)
    • Serum SGPT/ALT <3.0 x upper limits of normal (ULN)
    • Serum total bilirubin <1.5 x ULN
  • Subject must have a MUGA scan or echo with LVEF >50% within 6 months of enrollment.
  • Females of childbearing potential (FCBP) must have a negative serum pregnancy test should be done within 7 days of treatment initiation and a negative urine pregnancy test within the 24 hours prior to the first study drug administration
  • FCBP and male subjects who are sexually active with FCBP must agree to use 2 highly effective concomitant methods of contraception including a male condom during the study and for 90 days following the last dose of study treatment
  • Male subjects must agree to not donate sperm while taking carfilzomib and for 90 days after the last dose of carfilzomib.

EXCLUSION CRITERIA

  • Subject has a history of allergic reactions to compounds containing captisol, or Carfilzomib
  • Subject has a NYHA Class III or IV heart disease and/or a history of active unstable angina, congestive heart disease, severe uncontrolled cardiac arrhythmia, electrocardiographic evidence of acute ischemia, active conduction system abnormalities or myocardial infarction within 6 months prior to enrollment. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
  • Uncontrolled hypertension
  • Pulmonary hypertension
  • Subject has a known HIV or hepatitis A, B, or C positivity---ONLY IF ACTIVE
  • Subject has active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.
  • Subject has concurrent, uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place him/her at unacceptable risk, including, but not limited to, uncontrolled hypertension, uncontrolled diabetes, active uncontrolled infection, and/or acute chronic liver disease (i.e., hepatitis, cirrhosis).
  • Subject has ≥Grade 2 peripheral neuropathy.
  • Subject has been 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.
  • Subject has received radiation therapy within 3 weeks of enrollment Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.
  • Subject has had prior mobilization or stem cell transplant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03909412


Contacts
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Contact: Mariefel Vendivil 551-996-5828 Mariefel.Vendivil@Hackensackmeridian.org
Contact: Andrea Ortega 551-996-3923 Andrea.Ortega@Hackensackmeridian.org

Locations
Layout table for location information
United States, New Jersey
Hackensack Meridian Health - John Theurer Cancer Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Mariefel Vendivil    551-996-5828    Mariefel.Vendivil@Hackensackmeridian.org   
Contact: Andrea Ortega    551-996-3923    Andrea.Ortega@Hackensackmeridian.org   
Principal Investigator: David Vesole, MD, PhD         
Sponsors and Collaborators
Hackensack Meridian Health
Amgen
Publications:
Munshi NC, Tricot G, Barlogie B: Plasma cell neoplasms, in De Vita VT, Hellman S, Rosenberg SA (ed): Cancer : Principles & Practice on Oncology, 6th edition, Philadelphia, PA. Lippincott Williams & Wilkins, 2001, pp 2465-2499
Niesvizky R, Choy CG, Fine J, Glassman J, Reich L, Straus D, Zhu A, Michaeli J: Impact of initial response on disease progression following tandem peripheral blood stem cell transplants in patients with poor prognosis multiple myeloma. ASH December, 1998. Abstract # 2728.
Demo SD, Buchholz TJ, Laidig GL, Parlati F, Shenk KD, Smyth MS, et al. Biochemical and cellular characterization of the novel proteasome inhibitor PR-171. Blood 2005;106:455a, Abstract 1588.
Velcade® (bortezomib) [full prescribing information]. Cambridge, MA: Millennium Pharmaceuticals, Inc.; 2008.
Ivancsits D, Nimmanapali R, Sun M, Shenk K, Demo SD, Bennett MK, et al. The proteasome inhibitor PR-171 inhibits cell growth, induces apoptosis, and overcomes de novo and acquired drug resistance in human multiple myeloma cells. Blood 2006;106:452a.
Herve Avet-Loiseau eta al., Evaluation of Minimal Residual Disease (MRD) By Next Generation Sequencing (NGS) Is Highly Predictive of Progression Free Survival in the IFM/DFCI 2009 Trial. ASH annual meeting abstracts. Blood 2015 126:191

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Responsible Party: Hackensack Meridian Health
ClinicalTrials.gov Identifier: NCT03909412    
Other Study ID Numbers: Pro2018-0531
First Posted: April 10, 2019    Key Record Dates
Last Update Posted: September 16, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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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
Cyclophosphamide
Lenograstim
Sargramostim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents