ASCT With Nivolumab in Patients With Multiple Myeloma

Study Overview
=================
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.

Official Title
-----------------
Autologous Stem Cell Transplantation With Nivolumab in Patients With Multiple Myeloma

Conditions
-----------------
Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: Melphalan
* Drug: Nivolumab
* Procedure: Autologous Stem Cell Transplantation


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nivolumab, Melphalan, Autologous hematopoietic stem cell transplantation, Multiple Myeloma