Monitoring of Deep of Response During Lenalidomide Maintenance in MM Patients Achieving at Least Very Good Partial Response (MRD) (MRD)

• ClinicalTrials.gov Identifier: NCT03433365
• Recruitment Status: Completed
• First Posted: February 14, 2018
• Last Update Posted: November 6, 2018
• Sponsor: Fondazione EMN Italy Onlus
• Information provided by (Responsible Party): Fondazione EMN Italy Onlus

Study Description

Brief Summary:

This is an italian multicenter study to determine whether maintenance treatment with Lenalidomide-based regimen significantly increases the rate of molecular remission in patients achieving at least a VGPR after therapy with new drugs combination. No changing in the planned therapy will be made according to MRD results. A total of 70 patients with newly diagnosed MM who are 18 years of age or older and who meet all of the eligibility criteria may be enrolled in this study.

Potential study subjects will sign an informed consent prior undergoing any study related procedure. Patients enrolled in this study will receive Lenalidomide-based regimen as maintenance therapy according to their previous decided therapeutic schedule. All consecutive patients treated with Lenalidomide-based regimen as maintenance therapy and with inclusion criteria will be asked to participate to this study.

No additional drugs will be administrated for this study whose aim is to monitor the MRD on bone marrow aspirate and peripheral blood of patients during maintenance therapy with Lenalidomide-based regimen.

Condition or disease	Intervention/treatment
Multiple Myeloma	Other: MRD analysis

Detailed Description:

Patients entering the study will signed an informed consent and will undergo bone marrow aspiration and peripheral blood examination. On both these two tissues the MRD analysis reaching for myeloma cells.

During the treatment period, all patients will attend study center visits every 4 weeks, until development of confirmed Progressive Disease (PD). During this visits the patients will undergo physical evaluation and routine blood control will be performed to monitor response to therapy and side effects.

When a patient develops a PD requiring the beginning of a new treatment, the patient interrupts the MRD monitoring but will be followed for survival every 2 months via telephone or office visit.

Study Design

• Study Type: Observational
• Actual Enrollment: 70 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: Lenalidomide Maintenance in Multiple Myeloma Patients Achieving at Least VGPR After Induction Therapy: Minimal Residual Disease Monitoring
• Actual Study Start Date: March 2013
• Actual Primary Completion Date: March 2016
• Actual Study Completion Date: August 2017

Groups and Cohorts

Group/Cohort

Intervention/treatment

1; Potential study subjects will sign an informed consent prior undergoing any study related procedure. Patients enrolled in this study will receive Lenalidomide-based regimen as maintenance therapy according to their previous decided therapeutic schedule. All consecutive patients treated with Lenalidomide-based regimen as maintenance therapy and with inclusion criteria will be asked to participate to this study.

Other: MRD analysis; To collect 2 samples for MRD analysis in patients treated with Lenalidomide; Other Name: No intervention_Observational study

Outcome Measures

Primary Outcome Measures :

1. MRD conversion [ Time Frame: 2 years ]
   Rate of conversion from MRD positive to MRD negative during maintenance therapy (qualitative PCR approach)
2. Tumour load [ Time Frame: 2 years ]
   Rate of patients with a reducing or increasing tumour load during therapy (quantitative real time PCR approach)
3. Molecular relapse [ Time Frame: 2 years ]
   Rate of molecular relapse

Secondary Outcome Measures :

1. MRD negativity [ Time Frame: 2 years ]
   MRD negativity duration during lenalidomide maintenance treatment
2. Molecular relapse [ Time Frame: 2 years ]
   Time from diagnosis to molecular relapse. Evaluate if molecular relapse can be considered an early biomarker of relapse
3. Peripheral blood compared with bone marrow [ Time Frame: 2 years ]
   Evaluate MRD negativity on peripheral blood samples and compare it with MRD analysis conducted on bone marrow samples
4. Overall Survival [ Time Frame: 2 years ]
   Time from diagnosis to death in patients who achieved a molecular remission. Compare these results with the overall population

Biospecimen Retention:   Samples Without DNA

MRD determination will be performed using the tumor specific IgH rearrangement through allele specific real time PCR (ASO PCR). This technique is sensitive enough to detect one myeloma cells out of 105-106 normal cells and allows to perform quantitative evaluation too. This method for molecular MRD determination has already been published and in our laboratory has already been used for MRD analysis in MM. 2720 Thermal cyclers (Applied Biosystems, Carlsbad, California, USA) and the AbiPrism 7900HT (Applied Biosystems, Carlsbad, California, USA) will be employed to analyze MRD using qualitative and quantitative PCR approach. Both nested qualitative and real time quantitative PCR will be employed in this study.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Potential study subjects will sign an informed consent prior undergoing any study related procedure. Patients enrolled in this study will receive Lenalidomide-based regimen as maintenance therapy according to their previous decided therapeutic schedule.

Criteria

Inclusion Criteria:

• Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
• Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
• Patient has achieved at least a Very Good Partial Response (VGPR) before starting maintenance therapy
• Availability of a bone marrow sample at diagnosis stored in the Institution tissue bank to create patient-specific probes derived from IgH rearrangement
• Patients must receive Lenalidomide-based regimen as maintenance after a first line therapeutic approach
• Patient is 18 years old at the time of signing the informed consent
• Patient has a Karnofsky performance status ≥ 60%.
• Patient has a life-expectancy > 6 months
• Patient has HBV, HCV and HIV negative test.
• Patients must have normal ECG and NYHA ≤ 2; an evaluation of ejection fraction by ECHO or MUGA is optional
• Patients must be informed on acute and late toxicity of Lenalidomide treatment and must sign an informed consent.

Exclusion Criteria:

• Any serious medical condition, including the presence of laboratory abnormalities, which places the subject at an unacceptable risk if he or she participates in this study or confounds the experimental ability to interpret data from the study.
• Achieving of a PR or less before starting maintenance therapy
• Pregnant or lactating women. A serum β-hCG pregnancy test must be performed at the Screening visit, for female patients of child-bearing potential. If the test is positive, the patient must be excluded from the study. Confirmation that the patient is not pregnant must be established by a negative serum or urinary pregnancy test with the result obtained 1 day prior to the Baseline visit (or the day of the visit if results are available before drug delivery). A pregnancy test is not required for naturally post-menopausal women (who have not had menses at any time in the preceding 24 consecutive months) or surgically sterilised women (hysterectomy, bilateral ovariectomy, bilateral salpingectomy).

Contacts and Locations

Locations

Italy

AOU Città della Salute e della Scienza di Torino

Torino, Italy, 10126

Sponsors and Collaborators

Fondazione EMN Italy Onlus

More Information

• Responsible Party: Fondazione EMN Italy Onlus
• ClinicalTrials.gov Identifier: NCT03433365
• Other Study ID Numbers: RV-MM-PI-0694
• First Posted: February 14, 2018
• Last Update Posted: November 6, 2018
• Last Verified: November 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases