ASCT With Nivolumab in Patients With Multiple Myeloma

Autologous Stem Cell Transplantation With Nivolumab in Patients With Multiple Myeloma

This is an open-label, single center trial of Autologous Stem Cell Transplantation (ASCT) with nivolumab in multiple myeloma patients to determine the efficacy and safety of ASCT and PD1 inhibitor combination.

For this purpose, 30 multiple myeloma patients, who have received induction therapy and have achieved a partial response (PR), stable disease (SD) or progression, and thus have unfavorable prognosis, will be treated with nivolumab administered iv at a dose of 100 mg on days 3 before and 17 after high-dose melphalan with autologous stem cell transplantation.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Melphalan; Drug: Nivolumab; Procedure: Autologous Stem Cell Transplantation

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 197089
    • Boris V Afanasyev, MD, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects with MM (Multiple Myeloma)
• Partial response, stable disease or progression after induction therapy (including ASCT)
• Measurable disease
• Successful peripheral blood stem cell collection with G-CSF
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
• Signed informed consent
• Patients after first-line induction therapy

Exclusion Criteria:

• Another malignancy requiring treatment at the time of inclusion
• History of interstitial lung disease or pneumonitis
• Patients with any other known concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes; cardiovascular disease including congestive heart failure NYHA Class III or IV, myocardial infarction within 6 months, and poorly controlled hypertension) which, in the opinion of the investigator could compromise participation in the study
• Uncontrolled bacterial or fungal infection at the time of enrollment
• Pregnancy
• Somatic or psychiatric disorder making the patient unable to sign informed consent
• Active or prior documented autoimmune disease requiring systemic treatment
• Prior treatment with anti-PD-1, anti-PD-L1, or anti-CTLA4 therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mel+Nivo; Autologous Stem Cell Transplant Drug: Melphalan 140-200 mg/m^2, Nivolumab100 mg iv days -3, +17	Drug: Melphalan; iv infusion 70-100 mg/m2 on day -3, -2; Other Names: Alkeran; Drug: Nivolumab; iv infusion 100 mg on day -3, +17; Other Names: Opdivo; Procedure: Autologous Stem Cell Transplantation; peripheral blood stem cell transfusion at day 0

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response	Includes complete response, very good partial response, and partial response (based on IMWG criteria)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	PFS will be assessed with Kaplan-Meier method from the date of ASCT, with day 0 defined as date of stem cell infusion (in case of tandem transplant the 2nd of 2 transplants will be used) until the date of progression, defined as the date at which the patient starts the next line of therapy or the date of death.	12 months
Overall Survival (OS)	Will be assessed with Kaplan-Meier method from the date of ASCT, with day 0 defined as date of stem cell infusion (in case of tandem transplant the 2nd of 2 transplants will be used)	24 months
Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03	Toxicity parameters based on NCI CTCAE 4.03 grades: hematological toxicity (CBC), hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), fatigue (attending physician assessment), rash (attending physician assessment), colitis (attending physician assessment), pneumonitis (attending physician assessment), autoimmune disorders (level of hormones, presence of autoimmune antibodies, attending physician assessment).	12 months

Collaborators and Investigators

• Sponsor: St. Petersburg State Pavlov Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2017
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: September 21, 2017
• First Submitted That Met QC Criteria: September 22, 2017
• First Posted (Actual): September 25, 2017

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Nivolumab; Melphalan; Autologous hematopoietic stem cell transplantation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Melphalan
• Other Study ID Numbers: 11/17-n

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No