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

NCT03795597 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: 209274
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Autologous; Stem Cell Transplantation; Bone Marrow Transplant; Carfilzomib

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (10)

• 36 participants evaluated for response to treatment by testing blood for multiple myeloma levels.

  100 days

• 36 participants evaluated for progression by testing blood for multiple myeloma levels.

  3 years

• 36 participants evaluated for overall survival by clinical visit or contact by phone.

  3 years

• 36 participants evaluated for absolute neutrophil count by testing white blood cells levels.

  100 days

• 36 participants evaluated for platelet engraftment by testing platelet count in blood cells.

  100 days

Study Arms (5)

Carfilzomib IV at dose: 20 mg/m2

EXPERIMENTAL

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; Drug: Busulfan IV; Drug: Melphalan IV

Carfilzomib IV at dose: 27 mg/m2

EXPERIMENTAL

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; Drug: Busulfan IV; Drug: Melphalan IV

Carfilzomib IV at dose: 36 mg/m2

EXPERIMENTAL

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; Drug: Busulfan IV; Drug: Melphalan IV

Carfilzomib IV at dose: 45 mg/m2

EXPERIMENTAL

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; Drug: Busulfan IV; Drug: Melphalan IV

Carfilzomib IV at dose: 56 mg/m2

EXPERIMENTAL

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; Drug: Busulfan IV; Drug: Melphalan IV

Interventions

Carfilzomib DRUG

Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.

Also known as: Kyprolis

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

Busulfan IV DRUG

Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.

Also known as: Busulfex

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

Melphalan IV DRUG

Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.

Also known as: Alkeran

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

Eligibility Criteria

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

You may qualify if:

• 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 must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) less than or equal to 2.
• Acceptable heart function test.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Loyola University: lead
• Amgen: collaborator

Study Sites (1)

Loyola University Medical Center

Maywood, Illinois, 60153, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Busulfan; Melphalan

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)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Patrick Stiff, MD

  Loyola University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patrick Stiff, MD

CONTACT

708-327-3148; mailto:pstiff@lumc.edu

Mary Lee, RN

CONTACT

708-327-2241; mailto:mlee@luc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: October 17, 2018
• First Posted: January 8, 2019
• Study Start: May 22, 2019
• Primary Completion: November 1, 2022
• Study Completion: November 1, 2023
• Last Updated: April 26, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)