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

Multiple Myeloma Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03795597
• Other study ID #: 209274
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 22, 2019
• Est. completion date: November 1, 2023

Study information

• Verified date: April 2021
• Source: Loyola University
• Contact: Patrick Stiff, MD
• Phone: 708-327-3148
• Email: mailto:pstiff[@]lumc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: November 1, 2023
• Est. primary completion date: November 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
• Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
• Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.

Locations

Country	Name	City	State
United States	Loyola University Medical Center	Maywood	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Loyola University	Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	3 years
Primary	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.	3 years
Secondary	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.	100 days
Secondary	36 participants evaluated for progression by testing blood for multiple myeloma levels.	Progression Free Survival	3 years
Secondary	36 participants evaluated for overall survival by clinical visit or contact by phone.	Overall Survival	3 years
Secondary	36 participants evaluated for absolute neutrophil count by testing white blood cells levels.	Days to neutrophil engraftment: Absolute neutrophil count > 500/microliter	100 days
Secondary	36 participants evaluated for platelet engraftment by testing platelet count in blood cells.	Days to platelet engraftment: platelet count > 20,000/microliter untransfused	100 days
Secondary	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	100 days
Secondary	36 participants evaluated by the liver to assess Veno-occlusive disease and grading levels by using CTCAE v4.0.	Veno-occlusive disease	100 days
Secondary	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	3 years
Secondary	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	100 days
Secondary	36 participants evaluated for progression by testing urine for multiple myeloma levels.	Progression Free Survival	3 years