Pembrolizumab (MK-3475) in MM Patients With Residual Disease

NCT02636010 | Completed Phase 2 DMC

• 1 other identifier: GEM-PEMBRESID
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 11

Brief Summary

This is a national, multicenter, open label single-arm, non-comparative study that will determine the efficacy, safety and the changes in selected pharmacodynamics markers of MK-3475 monotherapy administered as consolidation therapy in MM patients who have achieved a response with a previous treatment but who still display some residual disease. For this purpose, 20 MM patients, who have received any treatment of limited duration either at diagnosis or at first relapse, and that have achieved a good response (≥VGPR) but with persistent residual disease (that is patients in VGPR, non-stringent CR, or MRD+ sCR), will be treated with MK-3475 monotherapy administered iv at a dose of 200 mg every three weeks for 1 year, with a potential expansion of 1 additional year of treatment in case of clinical benefit and patient agreement. Efficacy, safety and pharmacodynamic parameters will be evaluated to understand the role of this monoclonal antibody in this setting.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Efficacy of Pembrolizumab as measured by overall response rate manteinance

  2 years

Secondary Outcomes (2)

• Safety will be evaluated by assessing toxicity related to pembrolizumab

  2 years

• Efficacy as measured by minimal residual disease rate after two years of maintenance treatment with pembrolizumab

  2 years

Study Arms (1)

MK-3475 Pembrolizumab

EXPERIMENTAL

MK-3475 at a dose of 200 mg every three weeks for 1 year with a potential expansion of 1 additional year of treatment in case of clinical benefit and patient agreement

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Also known as: MK-3475

MK-3475 Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Performance status (ECOG) ≤ 2.
• 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
• Patients previously diagnosed with MM according to the IMWG Criteria (Blood 2011) who are in good response (≥VGPR) but with persistent residual disease after the end of any therapy administered for a limited duration of time either at 1st or 2nd line of therapy.
• Persistent disease is defined by either the presence of an M-Component by electrophoresis, positive immunofixation, abnormal FLC ratio or identification of pathological plasma cells by flow cytometry.
• At least 2 months for any non-transplant therapy or 3 months after ASCT, must relapse from the last dose of the previous treatment before being eligible to be included in the trial.
• Response must be confirmed to be stable between the end of the previous therapy and the initiation of the trial (see the time that must elapse in the previous criteria).
• Stable is defined as: No change in response according to the IMWG Criteria between these determinations; No evidence of increase or decrease (\> 25%) in M-component, provided the variation is \> 0.5 mg/dl; No evidence of increase or decrease (\> 25%) of the involved FLC, provided the ratio is abnormal and the absolute change is \> 10 mg/dL; No evidence of increase or decrease (\> 50%) of the percentage of pathological plasma cells by flow cytometry in the bone marrow provided the variation is \> 0.5%; No positivization or negativization of the electrophoresis or IFE between these determinations.
• In case of doubt, another determination separated at least 1 month after the last one is required to confirm the stability of the response, and this must be discussed with the DMC, prior to be eligible.

You may not qualify if:

• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or other antibody or drug specifically targeting T cell co-stimulation).
• Known hypersensitivity to pembrolizumab or any of its excipients.
• Non-adequate hematological or biochemical parameters as specified below:
• Hemoglobin \< 8.0 g/dl. Platelets count \< 75 x109/L without previous platelet transfusions in the last 7 days.
• Neutrophils (ANC) \<1 × 109/L without growth factor support (defined as no growth factor administration for at least 14 days prior to observation).
• Aspartate transaminase (AST): \> 2.5 x the upper limit range. Alanine transaminase (ALT): \> 2.5 x the upper limit range. Total bilirubin: \> 2 x the upper limit range. Creatinine clearance: \< 30 mL/min (measured or calculated with the Cockcroft and Gault formula).
• Absence of recovery from any significant non-hematological toxicity derived from previous treatments. The presence of alopecia and NCI CTCAE grade \< 2 symptomatic peripheral neuropathy is allowed.
• Pregnant or lactating women or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. Female subjects of childbearing potential should have a negative urine or serum pregnancy prior to study registration and re-tested within 72 hours prior to receiving the first dose of study medication.
• Men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, oral contraception). Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
• Previous history of any other malignancy in the last 5 years (except basal cell carcinoma, skin epithelioma or carcinoma in situ of any site).
• More than 2 prior lines of therapy for MM.
• Previous allogeneic stem cell transplantation.
• Other relevant diseases or adverse clinical conditions:
• Uncontrolled arterial hypertension or cardiac arrhythmias (i.e. requiring a change in medication within the last 3 months or a hospital admission within the past 6 months).
• History of significant neurological or psychiatric disorders. Active infection. Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis).

Sponsors & Collaborators

• PETHEMA Foundation: lead
• Merck Sharp & Dohme LLC: collaborator
• Adknoma Health Research: collaborator

Study Sites (11)

Hospital Germans Trias i Pujol

Badalona, Spain

Location

Hospital Clinic

Barcelona, Spain

Location

Hospital 12 de octubre

Madrid, Spain

Location

Hospital Ramón y Cajal

Madrid, Spain

Location

Hospital General Morales Messeguer

Murcia, Spain

Location

Hospital General Universitario Morales Messeguer

Murcia, Spain

Location

Clinica Universitaria de Navarra

Pamplona, Spain

Location

Hoapital Clinico Universitario Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Hospital Universitario Doctor Peset

Valencia, Spain

Location

Hospital Clinico de Zaragoza

Zaragoza, Spain

Location

Related Publications (1)

• Puig N, Corchete-Sanchez LA, Perez-Moran JJ, Davila J, Paino T, de la Rubia J, Oriol A, Martin-Sanchez J, de Arriba F, Blade J, Blanchard MJ, Gonzalez-Calle V, Garcia-Sanz R, Paiva B, Lahuerta JJ, San-Miguel JF, Mateos MV, Ocio EM. Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial. Cancers (Basel). 2020 Dec 3;12(12):3615. doi: 10.3390/cancers12123615.

  PMID: 33287189 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2015
• First Posted: December 21, 2015
• Study Start: June 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: February 20, 2020
• Last Updated: April 29, 2020

Record last verified: 2020-04

Locations

ES (11)