ASCT With Nivolumab in Patients With Multiple Myeloma

Sponsor

St. Petersburg State Pavlov Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03292263

Collaborator

(none)

Enrollment

Location

Arm

79.2

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Melphalan Drug: Nivolumab Procedure: Autologous Stem Cell Transplantation	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Autologous Stem Cell Transplantation With Nivolumab in Patients With Multiple Myeloma

Actual Study Start Date :

Apr 24, 2017

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Overall response [3 months]
Includes complete response, very good partial response, and partial response (based on IMWG criteria)

Secondary Outcome Measures

Progression free survival (PFS) [12 months]
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.
Overall Survival (OS) [24 months]
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)
Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03 [12 months]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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