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

NCT03909412 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Pro2018-0531
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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 Granulocyte colony-stimulating factor (G-CSF)

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Safety and tolerability will be assessed by clinical review of all relevant parameters including Adverse Events (CTCAE v4.0)

  24 Months

• Maximum tolerated dose (MTD)

  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

  28 Days

Study Arms (6)

Carfilzomib Mobilization - Dose Level 0

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Granulocyte Colony-Stimulating Factor

Carfilzomib Mobilization - Dose Level 1

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Granulocyte Colony-Stimulating Factor

Carfilzomib Mobilization - Dose Level 2

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Granulocyte Colony-Stimulating Factor

Carfilzomib Mobilization - Dose Level 3

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Granulocyte Colony-Stimulating Factor

Carfilzomib Mobilization - Dose Level 4

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Granulocyte Colony-Stimulating Factor

Carfilzomib Mobilization - Dose Level 5

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Granulocyte Colony-Stimulating Factor

Interventions

Carfilzomib DRUG

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.

Also known as: Kyprolis

Carfilzomib Mobilization - Dose Level 0; Carfilzomib Mobilization - Dose Level 1; Carfilzomib Mobilization - Dose Level 2; Carfilzomib Mobilization - Dose Level 3; Carfilzomib Mobilization - Dose Level 4; Carfilzomib Mobilization - Dose Level 5

Cyclophosphamide DRUG

Cyclophosphamide dosed at 2gm/m2 administered over 1 hour.

Also known as: Cytoxan

Carfilzomib Mobilization - Dose Level 0; Carfilzomib Mobilization - Dose Level 1; Carfilzomib Mobilization - Dose Level 2; Carfilzomib Mobilization - Dose Level 3; Carfilzomib Mobilization - Dose Level 4; Carfilzomib Mobilization - Dose Level 5

Dexamethasone DRUG

Dexamethasone 40mg IV/PO to be administered as a premedication.

Also known as: Decadron

Carfilzomib Mobilization - Dose Level 0; Carfilzomib Mobilization - Dose Level 1; Carfilzomib Mobilization - Dose Level 2; Carfilzomib Mobilization - Dose Level 3; Carfilzomib Mobilization - Dose Level 4; Carfilzomib Mobilization - Dose Level 5

Granulocyte Colony-Stimulating Factor DRUG

On day 7 subjects will initiate high dose G-CSF injections at 14mcg/kg daily (with a cap of 1440mcg daily).

Also known as: G-CSF, Filgrastim, Neupogen

Carfilzomib Mobilization - Dose Level 0; Carfilzomib Mobilization - Dose Level 1; Carfilzomib Mobilization - Dose Level 2; Carfilzomib Mobilization - Dose Level 3; Carfilzomib Mobilization - Dose Level 4; Carfilzomib Mobilization - Dose Level 5

Eligibility Criteria

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

You may qualify if:

• 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
• MRD positivity in peripheral blood by flow cytometry.
• Subject previously received treatment with Carfilzomib.
• 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 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)

You may not qualify if:

• 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.
• Known HIV infection, hepatitis C infection (subjects with hepatitis C that achieve a sustained virologic response after antiviral therapy are allowed), or hepatitis B infection (subjects with hepatitis B surface antigen or core antibody that achieve sustained virologic response with antiviral therapy are permitted with a requirement for regular monitoring for reactivation for the duration of treatment on the study).
• 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.

Sponsors & Collaborators

• Hackensack Meridian Health: lead

Study Sites (1)

Hackensack Meridian Health - John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Related Publications (24)

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MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Cyclophosphamide; Dexamethasone; Calcium Dobesilate; Granulocyte Colony-Stimulating Factor; Filgrastim

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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Central Study Contacts

Mariefel Vendivil

CONTACT

551-996-5828; Mariefel.Vendivil@hmhn.org

Geneva Khan

CONTACT

551-996-3923; Geneva.Khan@hmhn.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: February 19, 2019
• First Posted: April 10, 2019
• Study Start: October 8, 2019
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)