Study of AlloNK and rituximab with cyclophosphamide and fludarabine in adults with relapsing rheumatoid arthritis, inflammatory myopathies, systemic sclerosis, or Sjögren’s disease

2 1 1 1

What is this study about?

This study focuses on several rheumatologic diseases, including Rheumatoid Arthritis, Idiopathic Inflammatory Myopathies, Systemic Sclerosis, and Sjögren’s Disease. The research evaluates a new treatment approach combining AlloNK (natural killer cells derived from umbilical cord blood) with rituximab (a medication that targets specific immune cells) in patients whose conditions have not responded well to standard treatments.

Before receiving the main treatment, patients will undergo preparation with two medications: cyclophosphamide and fludarabine, which help reduce certain immune cells in the body. The purpose of this study is to determine if this combination treatment is safe and if it can help improve symptoms in patients with these hard-to-treat rheumatic conditions.

The treatment involves receiving the medications through intravenous infusion (delivery directly into a vein). Patients will receive multiple doses of the study medications over several weeks and will be monitored regularly to check how well the treatment works and to watch for any side effects. The study will track various measurements of disease activity and symptoms specific to each condition to determine if the treatment is effective.

1 Initial treatment preparation

Before starting the main treatment, you will receive lymphodepletion therapy with two medications: fludarabine phosphate and cyclophosphamide. These medications are given through an intravenous infusion (directly into a vein).

This preparation helps your body get ready for the cell therapy that follows.

2 Main treatment phase

The main treatment consists of two parts given through intravenous infusion:

First, you will receive AlloNK® (special cells derived from umbilical cord blood that have been processed in a laboratory)

Then, you will receive rituximab, a medication that targets specific cells in your immune system

3 Monitoring period

Your health will be regularly monitored through various tests and examinations for up to 52 weeks

The medical team will track your progress using specific measurements related to your condition:

For Rheumatoid Arthritis: Disease activity score assessment

For Inflammatory Muscle Diseases: Muscle strength and disease activity measurements

For Systemic Sclerosis: Skin thickness and organ involvement assessment

For Sjögren’s Disease: Disease activity index monitoring

4 Safety assessments

Throughout the study, regular safety checks will include:

Physical examinations

Blood tests

Heart activity monitoring (ECG)

Vital signs measurements

Monitoring for any side effects or reactions to the treatment

Who Can Join the Study?

Age 18 years or older
Must be able to understand and provide written consent for the study
Must be willing to follow study procedures
Must use effective contraception methods during the trial and for 1 year after treatment:
- For women: hormonal contraception, intrauterine devices, tubal ligation, or abstinence
- For men: vasectomy, barrier methods, or abstinence
Must have adequate lung function with DLCO (lung capacity test) ≥ 60% and FVC (breathing capacity) ≥ 70%
Heart function must show LVEF (pumping strength) ≥ 45% with no fluid around the heart
Must have acceptable blood test results including:
- Adequate white blood cell count
- Adequate platelet count
- Adequate hemoglobin levels
- Adequate kidney function
- Acceptable liver function tests
For patients with Rheumatoid Arthritis:
- Must meet specific diagnostic criteria
- Must have positive blood tests for RF or ACPA
- Must have active joint inflammation
- Must have tried and failed previous treatments
For patients with Inflammatory Muscle Disease:
- Must meet specific diagnostic criteria
- Must have specific antibodies in blood
- Must have tried and failed previous treatments
For patients with Systemic Sclerosis:
- Must meet specific diagnostic criteria
- Must have skin involvement and organ problems
- Symptoms must have started within last 3 years
For patients with Sjögren’s Disease:
- Must meet specific diagnostic criteria
- Must have active disease symptoms
- Must have adequate saliva production

Who Cannot Join the Study?

History of allergic reactions to rituximab (a medication used to treat certain autoimmune conditions)
Active or chronic infections, including:
- Hepatitis B (liver infection)
- Hepatitis C (liver infection)
- HIV (human immunodeficiency virus)
- Tuberculosis (bacterial infection affecting lungs)
Severe heart conditions or uncontrolled high blood pressure
Active cancer or history of cancer in the past 5 years (except successfully treated skin cancer)
Pregnant or breastfeeding women
Severe kidney or liver problems
Mental health conditions that could affect ability to provide informed consent
Participation in other clinical trials within the past 30 days
Use of live vaccines (vaccines containing weakened but living forms of viruses or bacteria) within 4 weeks before study start
Substance abuse or alcohol dependency within the past year
Inability to follow study procedures or attend required visits

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy
Oncopole Claudius Regaud	Toulouse	France
Unidade Local De Saúde De Santa Maria, E.P.E.	Lisbon	Portugal

Other Sites

Site Name	City	Country
Unidade Local De Saude De Gaia/Espinho E.P.E.	Vila Nova De Gaia	Portugal
University Multiprofile Hospital For Active Treatment Saint Georgi EAD	Plovdiv	Bulgaria
Szpital Uniwersytecki Nr 2 Im Dr Jana Biziela W Bydgoszczy	Bydgoszcz	Poland
Spitalul Clinic Colentina Bucuresti	Bucharest	Romania
Ospedale San Raffaele S.r.l.	Milan	Italy
Rheinische Friedrich-Wilhelms-Universitaet Bonn	Bonn	Germany
University Multiprofile Hospital For Active Treatment St. Ivan Rilski EAD	Sofia	Bulgaria
Universita Degli Studi Di Brescia	Brescia	Italy
Wyuaueyavdj Wkrzguayokufauxaetvg Cahrrlo Ogfozpbjo I Ttewuceqercdd Ii Mvumjkzrsci W Lesip	Lodz	Poland
Nsdzltzd Iashkezp Gyxgabhvf Rvdnwcbhsyjp I Rbxddpfxiuwmh If Pufez Dp Hbpe Myml Eqfnsayw Rmhopbu	Warsaw	Poland
Hwgzdaxk Skauv Ehkk	Montpellier	France
Slqzgrqj Cepfjv &ppgqlqtrv Ie Crwfyggqvqpulkuqbv	Bucharest	Romania
Apjeawqrhu Prbxkivy Hjuuzckd Da Mpvsjjzqw	Marseille	France
Kdooihcx dfy Ukidagebjwgq Mcpghssi Azq	Munich	Germany

Trial status

Country	Status	Recruitment Start
Bulgaria	Recruiting	30.11.2025
France	Recruiting	30.11.2025
Germany	Recruiting	30.11.2025
Italy	Recruiting	30.11.2025
Poland	Recruiting	30.11.2025
Portugal	Recruiting	30.11.2025
Romania	Recruiting	30.11.2025
Spain	Recruiting	30.11.2025

Trial locations

Investigated drugs:

AlloNK is an innovative cell therapy derived from cord blood NK cells (Natural Killer cells). It is designed to help treat patients with B-cell dependent rheumatologic diseases by targeting abnormal B cells in the immune system.

Rituximab is an antibody medication that targets specific B cells in the immune system. It is commonly used to treat various autoimmune conditions and works by reducing the number of B cells that may be causing inflammation.

Cyclophosphamide is a medication used for lymphodepletion (reducing the number of lymphocytes in the body). It helps prepare the patient’s immune system before receiving the cell therapy treatment.

Fludarabine is also used for lymphodepletion and works together with cyclophosphamide. This medication helps create space in the immune system for the new cell therapy to work more effectively.

Rheumatoid Arthritis (RA) – A chronic inflammatory condition that affects multiple joints throughout the body. The immune system attacks the joint lining, causing swelling, stiffness, and pain. Over time, this inflammation can lead to joint damage and deformity. The condition typically affects joints symmetrically on both sides of the body.

Idiopathic Inflammatory Myopathies (IIMs) – A group of disorders causing muscle inflammation of unknown origin. These conditions lead to progressive muscle weakness, primarily affecting the muscles closest to the trunk of the body. Patients experience difficulty with basic movements such as climbing stairs, rising from chairs, or lifting objects.

Systemic Sclerosis (SSc) – A connective tissue disorder characterized by hardening and tightening of the skin and internal organs. The condition causes the body to produce too much collagen, leading to tissue thickening. It can affect multiple body systems, including the skin, blood vessels, and internal organs.

Sjögren’s Disease (SjD) – An autoimmune disorder that primarily affects the moisture-producing glands. The condition typically causes dry eyes and dry mouth, but can also affect other parts of the body. The immune system attacks healthy tissue, particularly the glands that produce tears and saliva.

Trial ID:

2025-520461-41-00

Protocol code:

AB-101-05

NCT ID:

NCT06991114

Trial Phase:

Therapeutic exploratory (Phase II)

Other Trials to Consider

#1 Clinical Trials Search in Europe

Study of AlloNK and rituximab with cyclophosphamide and fludarabine in adults with relapsing rheumatoid arthritis, inflammatory myopathies, systemic sclerosis, or Sjögren’s disease

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?