Intensified Treatment With Carfilzomib in Myeloma Patients Still PET-positive After First Line Treatment. (CONPET)

KRd Consolidation in Myeloma Patients With a Positive PET-CT After Standard First Line Treatment. A Phase II Study

A PET-CT will be performed on patients with myeloma after a standard first-line treatment. The PET-positive patients will receive 4 cycles of Carfilzomb-Revlimid-Dexamethason (KRd), before a new PET-CT will be performed.

Study Overview

• Status: Active, not recruiting
• Conditions: Myeloma
• Intervention / Treatment: Drug: Carfilzomib; Drug: Lenalidomide; Device: PET-CT; Drug: Dexamethasone

Detailed Description

Patients will be evaluated for inclusion after finishing first-line therapy, or after a sufficient amount of treatment in first-line, and a sufficient respons (VGPR). Eligible performed regimens are defined in the protocol. All patients will perform a PET-CT, and PET-negative patients will be excluded from protocol treatment. The PET-positive patients will do a minimal residual disease (MRD-)evaluation in the bone marrow before entering treatment. After 4 28day cycles of Carfilzomib-Revlimid-Dexamethason, a new MRD and a new PET-CT will be performed, as measures of outcome. Patients will continue treatment as written in the protocol.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anna Lysén, MSc; Phone Number: +4747246569; Email: annaly@ous-hf.no
• Study Contact Backup: Name: Fredrik H Schjesvold, MD PhD; Phone Number: +4799697796; Email: fredrikschjesvold@gmail.com

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Copenhagen University Hospital, Rigshospitalet
  • Odense, Denmark
    • Odense University Hospital
• Norway
  • Oslo, Norway
    • Oslo University Hospital
• Sweden
  • Lund, Sweden
    • Skåne University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Prior confirmed diagnosis of multiple myeloma (2014).

2. Received standard first line treatment with at least partial response. Standard first line treatment is defined as

   • VRD, VTD or VCD followed by ASCT, or
   • MPV at least 6 cycles, or no further reduction in monoclonal component the last 2 cycles, or
   • Rd at least 9 cycles or no further reduction in monoclonal component the last 2 cycles.
3. Carfilzomib naïve.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
5. Absolute neutrophil count (ANC) ≥ 0,5 x 109/L) and platelet count >35 x 109/L.
6. At least very good partial remission (VGPR) from first line treatment

Exclusion Criteria:

1. Change of first line treatment because of stabile or progressive disease.
2. Major surgery within 28 days before enrollment.
3. Radiotherapy within 14 days before enrollment, but if the involved field is small, 7 days will be considered a sufficient interval before onset of the treatment.
4. Glucocorticoid therapy within the 14 days prior to inclusion that exceeds a cumulative dose of 160 mg dexamethasone or 1000 mg prednisone.
5. Central nervous system involvement.
6. Uncontrolled heart disease, including congestive heart failure (NYHA III-IV), uncontrolled angina pectoris, uncontrolled conduction abnormalities, acute diffuse infiltrative pulmonary disease, pericardial disease or myocardial infarction within 6 months prior to enrollment
7. Uncontrolled hypertension or uncontrolled diabetes despite medication
8. Active hepatitis B or C infection or known human immunodeficiency virus (HIV) positivity.
9. Another active malignancy. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
10. Primary plasma cell leukemia, systemic AL amyloidosis, Waldenströms macroglobulinemia, POEMS syndrome

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: PET-CT-positive patients; Carfilzomib 20/36mg/m2 days 1,2,8,9,15,16 Lenalidomide 25mg days 1-21 Dexamethasone 40mg days 1,8,15,22 28 day cycles 4 cycles	Drug: Carfilzomib; See in arm description; Drug: Lenalidomide; See in arm description; Device: PET-CT; See in arm description; Drug: Dexamethasone; See in arm description

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PET negativity after induction	How many of PET positive patients will become PET negative after treatment	1 month after induction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PET correlation with MRD Euroflow	Before intervention all patients are PET-CT positive. The investigators will measure minimal residual disease (MRD) with immuno-flow cytometry, at the same timepoint, and describe how many of the PET-CT patients, are MRD-negative and how many are MRD-positive. After the intervention the investigators will again do PET-CT and MRD by flow cytometry. The investigators will then describe how many PET-positive patients are MRD-positive and how many are MRD-negative. As well, the investigators will describe the same in the PET-CT negative patients.	1 month after induction

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Nordic Myeloma Study Group

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2018
• Primary Completion (Actual): November 1, 2021
• Study Completion (Anticipated): November 1, 2026

Study Registration Dates

• First Submitted: September 8, 2017
• First Submitted That Met QC Criteria: October 15, 2017
• First Posted (Actual): October 19, 2017

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: May 4, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• 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; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Lenalidomide
• Other Study ID Numbers: NMSG25/16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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