Busulfan, Melphalan, Escalating Carfilzomib Conditioning Auto Stem Cell Transplantation for Multiple Myeloma (MM) (BuMelCarAuto)

April 23, 2021 updated by: Patrick Stiff, Loyola University

Phase I/II Study Utilizing High Dose Busulfan and Melphalan With Escalating Carfilzomib as Conditioning in Autologous Peripheral Blood Stem Cell Transplantation for Patients With Multiple Myeloma

In this protocol, the investigators hypothesize that the combination of intravenous busulfan and melphalan with carfilzomib will be an effective preparative regimen with acceptable toxicity for participants with multiple myeloma who are candidates for autologous stem cell transplantation. To test this hypothesis, the investigators designed a phase I/II trial combining IV busulfan 130 mg/m2 plus melphalan 140 mg combined with escalating doses of carfilzomib ranging from 20 mg/m2 to 45 mg/m2. These results will be compared with the center's historical controls of participants treated with melphalan, busulfan and bortezomib.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Participants enrolled in this study protocol will receive daily intravenous (IV) infusions of carfilzomib for a total of 4 days (Day-9, -8 and Days -2, -1). The first two daily infusions will be given at a fixed dose of 20 mg/m2 and the final two doses will be escalated from the standard dose of 27 mg/m2 to 56 mg/m2 in a Phase I design, based on toxicity. The busulfan will be administered for 2 days over 3 hours from D-7, -6, at 130 mg/m2 . This dose was found to be safe and equivalent to the standard daily dose of 3.2 mg/kg. The 3rd and 4th daily doses of IV Busulfan will be adjusted in order to yield a systemic plasma drug exposure represented by a daily area under the plasma concentration versus time curve (AUC) of approximately 5,000 millimoles-minute per dose (mM-min). These targeted plasma concentration of IV busulfan will be based on pharmacokinetics studies performed during the first day of IV busulfan. Melphalan will be given at a dose of 140 mg/m2 on Day -3. Each cohort will start with a goal of accruing three patients to determine the dose limiting toxicity.

Study Type

Interventional

Enrollment (Anticipated)

36

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Illinois
      • Maywood, Illinois, United States, 60153
        • Recruiting
        • Loyola University Medical Center
        • Contact:
          • Mary Lee, RN
          • Phone Number: 708-327-2241
          • Email: mlee@luc.edu
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Participants must be greater than or equal to 18 years of age.
  • Participants must have been diagnosed with multiple myeloma in a first or subsequent remission and have undergone a successful pre-transplant work up and are otherwise eligible for an autotransplant with a busulfan/melphalan preparative regimen at Loyola University Medical Center.
  • Participants may receive this preparative regimen if in first or subsequent remission. Participants may enter if they have received a prior autologous stem cell transplant and this therapy produced a remission that lasted greater than 18 months before progression of disease. Participants who have undergone prior allogeneic transplantation are excluded.
  • All participants must have responsive disease as defined by a Partial Response or greater to most recent conventional regimen.
  • Participants receiving prior carfilzomib will be eligible for inclusion provided they demonstrated responsive disease to this agent and either had a remission that lasted greater than 6 months after its discontinuance, or if in remission after a carfilzomib containing regimen administered to qualify for transplant.
  • Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) less than or equal to 2.
  • Acceptable heart function test.

Exclusion Criteria:

  • Participants must not have below normal kidney function.
  • Participants must not have below normal liver function.
  • Participants must not have active bacterial, fungal, or viral infection.
  • Participants must not have severe lung function.
  • Participants must not have Grade 2 or greater peripheral neuropathy.
  • Participants must not have uncontrolled hypertension.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Carfilzomib IV at dose: 20 mg/m2
The participants will receive Carfilzomib IV at dose: 20 mg/m2 on days -9 and -8 over 30 minutes. The participant will receive Busulfan IV over 3 hours every 24 hours for a total of 4 doses from Day -6 to Day -3 and Melphalan IV over 15-30 minutes for one dose on day -3.The participants will receive stem cell infusion on Day 0 and Granulocyte-Colony stimulating factor (G-CSF) given daily until engraftment occurs.
Drug: Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Other Names:
  • Kyprolis
Drug: Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Other Names:
  • Busulfex
Drug: Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Other Names:
  • Alkeran
Experimental: Carfilzomib IV at dose: 27 mg/m2
The participants will receive Carfilzomib IV at dose: 27 mg/m2 on days -9 and -8 over 30 minutes. The participant will receive Busulfan IV over 3 hours every 24 hours for a total of 4 doses from Day -6 to Day -3 and Melphalan IV over 15-30 minutes for one dose on day -3.The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs.
Drug: Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Other Names:
  • Kyprolis
Drug: Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Other Names:
  • Busulfex
Drug: Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Other Names:
  • Alkeran
Experimental: Carfilzomib IV at dose: 36 mg/m2
The participants will receive Carfilzomib IV at dose: 36 mg/m2 on days -9 and -8 over 30 minutes. The participant will receive Busulfan IV over 3 hours every 24 hours for a total of 4 doses from Day -6 to Day -3 and Melphalan IV over 15-30 minutes for one dose on day -3.The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs.
Drug: Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Other Names:
  • Kyprolis
Drug: Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Other Names:
  • Busulfex
Drug: Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Other Names:
  • Alkeran
Experimental: Carfilzomib IV at dose: 45 mg/m2
The participants will receive Carfilzomib IV at dose: 45 mg/m2 on days -9 and -8 over 30 minutes. The participant will receive Busulfan IV over 3 hours every 24 hours for a total of 4 doses from Day -6 to Day -3 and Melphalan IV over 15-30 minutes for one dose on day -3.The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs.
Drug: Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Other Names:
  • Kyprolis
Drug: Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Other Names:
  • Busulfex
Drug: Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Other Names:
  • Alkeran
Experimental: Carfilzomib IV at dose: 56 mg/m2
The participants will receive Carfilzomib IV at dose: 56 mg/m2 on days -9 and -8 over 30 minutes. The participant will receive Busulfan IV over 3 hours every 24 hours for a total of 4 doses from Day -6 to Day -3 and Melphalan IV over 15-30 minutes for one dose on day -3.The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs.
Drug: Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Other Names:
  • Kyprolis
Drug: Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Other Names:
  • Busulfex
Drug: Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Other Names:
  • Alkeran

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
36 participants evaluated for safety with treatment-related adverse events and grading by using CTCAE v4.0.
Time Frame: 3 years
To determine the maximal tolerated dose of carfilzomib when added to busulfan and melphalan as a preparative regimen for high dose therapy with autologous hematopoietic transplantation for patients with multiply myeloma.
3 years
36 participants evaluated for tolerability with treatment-related adverse events and grading by using CTCAE v4.0.
Time Frame: 3 years
To determine the maximal tolerated dose of carfilzomib when added to busulfan and melphalan as a preparative regimen for high dose therapy with autologous hematopoietic transplantation for patients with multiply myeloma.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
36 participants evaluated for response to treatment by testing blood for multiple myeloma levels.
Time Frame: 100 days
To evaluate complete, very good partial, partial and stable disease response rate for both clinical and biologic endpoints.
100 days
36 participants evaluated for progression by testing blood for multiple myeloma levels.
Time Frame: 3 years
Progression Free Survival
3 years
36 participants evaluated for overall survival by clinical visit or contact by phone.
Time Frame: 3 years
Overall Survival
3 years
36 participants evaluated for absolute neutrophil count by testing white blood cells levels.
Time Frame: 100 days
Days to neutrophil engraftment: Absolute neutrophil count > 500/microliter
100 days
36 participants evaluated for platelet engraftment by testing platelet count in blood cells.
Time Frame: 100 days
Days to platelet engraftment: platelet count > 20,000/microliter untransfused
100 days
36 participants evaluated by oral exam to assess mucositis events and grading levels by using CTCAE v4.0.
Time Frame: 100 days
Mucositis: CTCAE v 4.0 grade and severity
100 days
36 participants evaluated by the liver to assess Veno-occlusive disease and grading levels by using CTCAE v4.0.
Time Frame: 100 days
Veno-occlusive disease
100 days
36 participants evaluated by a physical exam to assess peripheral neuropathy and grading by using CTCAE v4.0.
Time Frame: 3 years
Peripheral neuropathy greater than or equal to CTCAE V 4.0 Grade 3
3 years
36 participants evaluated for response to treatment by testing urine for multiple myeloma levels.
Time Frame: 100 days
To evaluate complete, very good partial, partial no stable disease response rate for both clinical and biologic endpoints
100 days
36 participants evaluated for progression by testing urine for multiple myeloma levels.
Time Frame: 3 years
Progression Free Survival
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Loyola University

Collaborators

Amgen

Investigators

  • Principal Investigator: Patrick Stiff, MD, Loyola University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 22, 2019

Primary Completion (Anticipated)

November 1, 2022

Study Completion (Anticipated)

November 1, 2023

Study Registration Dates

First Submitted

October 17, 2018

First Submitted That Met QC Criteria

January 3, 2019

First Posted (Actual)

January 8, 2019

Study Record Updates

Last Update Posted (Actual)

April 26, 2021

Last Update Submitted That Met QC Criteria

April 23, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 209274

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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