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

Primary Purpose

Multiple Myeloma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Carfilzomib
Busulfan IV
Melphalan IV
Sponsored by
Loyola University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Autologous, Stem Cell Transplantation, Bone Marrow Transplant, Carfilzomib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Loyola University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Carfilzomib IV at dose: 20 mg/m2

Carfilzomib IV at dose: 27 mg/m2

Carfilzomib IV at dose: 36 mg/m2

Carfilzomib IV at dose: 45 mg/m2

Carfilzomib IV at dose: 56 mg/m2

Arm Description

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

36 participants evaluated for safety with treatment-related adverse events and grading by using CTCAE v4.0.
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.
36 participants evaluated for tolerability with treatment-related adverse events and grading by using CTCAE v4.0.
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.

Secondary Outcome Measures

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

Full Information

First Posted
October 17, 2018
Last Updated
April 23, 2021
Sponsor
Loyola University
Collaborators
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT03795597
Brief Title
Busulfan, Melphalan, Escalating Carfilzomib Conditioning Auto Stem Cell Transplantation for Multiple Myeloma (MM)
Acronym
BuMelCarAuto
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Recruiting
Study Start Date
May 22, 2019 (Actual)
Primary Completion Date
November 1, 2022 (Anticipated)
Study Completion Date
November 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Loyola University
Collaborators
Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, Autologous, Stem Cell Transplantation, Bone Marrow Transplant, Carfilzomib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Busulfan IV over 3 hours every 24 hours for a total of 4 doses from D-6 to D-3. First two daily infusions will be given at a fixed dose of 3.2 mg/kg over 3 hours from D-6 to D-5. The 3rd and 4th daily doses will be adjusted to an AUC of approximately 5,000 mMol-min per dose. Melphalan 140 mg/ m2 IV over 15-30 minutes for one dose on day -3. Carfilzomib administration will follow a Phase I dose escalation design. Each cohort will start with a goal of accruing three patients to determine the dose limiting toxicities. Once the Maximum Tolerated Dose is established an expansion cohort will be treated to include a total of 10 additional patients.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Carfilzomib IV at dose: 20 mg/m2
Arm Type
Experimental
Arm Description
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.
Arm Title
Carfilzomib IV at dose: 27 mg/m2
Arm Type
Experimental
Arm Description
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.
Arm Title
Carfilzomib IV at dose: 36 mg/m2
Arm Type
Experimental
Arm Description
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.
Arm Title
Carfilzomib IV at dose: 45 mg/m2
Arm Type
Experimental
Arm Description
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.
Arm Title
Carfilzomib IV at dose: 56 mg/m2
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Carfilzomib
Other Intervention Name(s)
Kyprolis
Intervention Description
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
Intervention Type
Drug
Intervention Name(s)
Busulfan IV
Other Intervention Name(s)
Busulfex
Intervention Description
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
Intervention Type
Drug
Intervention Name(s)
Melphalan IV
Other Intervention Name(s)
Alkeran
Intervention Description
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
Primary Outcome Measure Information:
Title
36 participants evaluated for safety with treatment-related adverse events and grading by using CTCAE v4.0.
Description
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.
Time Frame
3 years
Title
36 participants evaluated for tolerability with treatment-related adverse events and grading by using CTCAE v4.0.
Description
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.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
36 participants evaluated for response to treatment by testing blood for multiple myeloma levels.
Description
To evaluate complete, very good partial, partial and stable disease response rate for both clinical and biologic endpoints.
Time Frame
100 days
Title
36 participants evaluated for progression by testing blood for multiple myeloma levels.
Description
Progression Free Survival
Time Frame
3 years
Title
36 participants evaluated for overall survival by clinical visit or contact by phone.
Description
Overall Survival
Time Frame
3 years
Title
36 participants evaluated for absolute neutrophil count by testing white blood cells levels.
Description
Days to neutrophil engraftment: Absolute neutrophil count > 500/microliter
Time Frame
100 days
Title
36 participants evaluated for platelet engraftment by testing platelet count in blood cells.
Description
Days to platelet engraftment: platelet count > 20,000/microliter untransfused
Time Frame
100 days
Title
36 participants evaluated by oral exam to assess mucositis events and grading levels by using CTCAE v4.0.
Description
Mucositis: CTCAE v 4.0 grade and severity
Time Frame
100 days
Title
36 participants evaluated by the liver to assess Veno-occlusive disease and grading levels by using CTCAE v4.0.
Description
Veno-occlusive disease
Time Frame
100 days
Title
36 participants evaluated by a physical exam to assess peripheral neuropathy and grading by using CTCAE v4.0.
Description
Peripheral neuropathy greater than or equal to CTCAE V 4.0 Grade 3
Time Frame
3 years
Title
36 participants evaluated for response to treatment by testing urine for multiple myeloma levels.
Description
To evaluate complete, very good partial, partial no stable disease response rate for both clinical and biologic endpoints
Time Frame
100 days
Title
36 participants evaluated for progression by testing urine for multiple myeloma levels.
Description
Progression Free Survival
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Patrick Stiff, MD
Phone
708-327-3148
Email
mailto:pstiff@lumc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Mary Lee, RN
Phone
708-327-2241
Email
mailto:mlee@luc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Stiff, MD
Organizational Affiliation
Loyola University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patrick Stiff, MD
Phone
708-327-3148
Email
pstiff@lumc.edu
First Name & Middle Initial & Last Name & Degree
Mary Lee, RN
Phone
708-327-2241
Email
mlee@luc.edu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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