Assessment of tolerance and effectiveness of total body irradiation and cladribine before allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia and myelodysplastic syndromes

2024-517477-24-00 Protocol 20-NIO-0001 Therapeutic exploratory (Phase II) Ongoing, recruitment ended

Start 17 Feb 2022 · Status Ongoing, recruitment ended · 1 EU/EEA countries · 1 sites · Protocol 20-NIO-0001

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ongoing, recruitment ended
Participants planned 40
Countries 1
Sites 1

Acute myeloid leukemia, myelodysplastic syndromes

The main objective of the CLARA STUDY is to assess the tolerance and effectiveness of total body irradiation and cladribine in adult patients diagnosed with AML and myelodysplastic syndromes. The primary research question of this project is to determine the percentage of patients with progression-free survival in 24 mo…

Key facts

Sponsor
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Participant type
Patients
Age range
18-64 years
Gender
Male and Female
Therapeutic area
Diseases [C] - Neoplasms [C04]
Trial duration
17 Feb 2022 → ongoing
Decision date (initial)
2024-11-18
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Medical Research Agency

External identifiers

EU CT number
2024-517477-24-00
EudraCT number
2020-005325-82
ClinicalTrials.gov
NCT04861207

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The main objective of the CLARA STUDY is to assess the tolerance and effectiveness of total body irradiation and cladribine in adult patients diagnosed with AML and myelodysplastic syndromes. The primary research question of this project is to determine the percentage of patients with progression-free survival in 24 month FU

Secondary objectives 1

  1. There are several secondary objectives of the clinical trial defined, as: the determining of the percentage of adverse events in the whole FU period, the probability of the 24-month overall survival, the probability of disease recurrence, the rate of mortality unrelated with the disease recurrence, the likelihood of acute and chronic graft-versus-host disease development as well as the time of neutrophil and platelet implantation.

Conditions and MedDRA coding

Acute myeloid leukemia, myelodysplastic syndromes

VersionLevelCodeTermSystem organ class
20.0 HLT 10028536 Myelodysplastic syndromes 10029104
21.0 LLT 10000886 Acute myeloid leukemia 10029104

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. Age between 18 and 60 years (inclusive).
  2. Patient is a candidate for allo-HSCT due to AML (intermediate or high risk AML in complete remission, low risk with positive MRD) or high risk myelodysplastic syndrome.
  3. Demonstration of chemosensitivity in the case of treatment regimens with cladribine in induction therapy.
  4. Patient signed informed consent form (ICF) prior to any study related screening procedures are performed.
  5. Patient has ECOG performance status score of 0 or 1.
  6. Patient is a candidate for allo-HSCT from sibling or unrelated donor (full matched or 9/10 mismatched) or from haploidentical donor.

Exclusion criteria 10

  1. Has recived more than 1 allo-HCT.
  2. Presence of active uncontrolled infection (i.e. sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection).
  3. Known active HIV, HBV or HCV infection (positive PCR test) or risk of HBV reactivation (HBsAg positive).
  4. Presence of active disease in AML patients.
  5. History or current diagnosis for uncontrolled or significant cardiac or pulmonary disease.
  6. Presence of severely renal or liver dysfunction (creatinine, ALT, AST or bilirubin concentration > 3.0 ULN (upper limit of normal).
  7. Currently pregnancy or breast feeding.
  8. Treatment of any other investigational agent in the same time as this study.
  9. Known allergies, hypersensivity, or intolerance to cladribine or similar compounds.
  10. Women of childbearing potential who do not agree tmoust use two effective methods of contraception.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The probability of progression-free survival in 24 month FU.

Secondary endpoints 6

  1. Frequency of adverse events in 24 month FU.
  2. 24-month overall survival probability.
  3. Disease recurrence probability.
  4. Mortality unrelated with disease recurrence.
  5. Likelihood of acute and chronic graft-versus-host disease.
  6. Time of neutrophil and platelet implantation.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

BIODRIBIN, 1 mg/ml, roztwór do infuzji

PRD802229 · Product

Active substance
Cladribine
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
SOLUTION FOR INFUSION
Max daily dose
5 mg/m2 milligram(s)/square meter
Max total dose
25 mg/m2 milligram(s)/square meter
Max treatment duration
5 Day(s)
Authorisation status
Authorised
ATC code
L01BB04 — CLADRIBINE
Marketing authorisation
R/7134
MA holder
SIEĆ BADAWCZA ŁUKASIEWICZ - INSTYTUT CHEMII PRZEMYSŁOWEJ IMIENIA PROFESORA IGNACEGO MOŚCICKIEGO
MA country
Poland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Sponsor organisation
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Address
Ul. Wybrzeze Armii Krajowej 15
City
Gliwice
Postcode
44-102
Country
Poland

Scientific contact point

Organisation
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Contact name
Clinical Research Support Center

Public contact point

Organisation
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Contact name
Clinical Research Support Center

Third parties 1

OrganisationCity, countryDuties
KCRI Sp. z o.o.
ORG-100027098
Cracow, Poland On site monitoring, Code 11, Code 12, Code 5, Data management, E-data capture, Code 8

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Poland Ongoing, recruitment ended 40 1
Rest of world 0

Investigational sites

Poland

1 site · Ongoing, recruitment ended
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Klinika Transplantacji Szpiku i Onkohematologii, Ul. Wybrzeze Armii Krajowej 15, 44-102, Gliwice

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Poland 2022-02-17 2022-02-17 2025-01-31

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_202451747724_Addendum_blinded 1.0
Protocol (for publication) D1_Protocol_202451747724_blinded 1.0
Recruitment arrangements (for publication) K1_Recruitment arrangement_2024-517477-24 1.0
Recruitment arrangements (for publication) K1_Recruitment arrangements_for publication 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF_blinded 2.0
Subject information and informed consent form (for publication) L1_SIS and ICF_for publication 3.0
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Biodribin N/A
Synopsis of the protocol (for publication) D1_Protocol synopsis_EN_202451747724_blinded 1.0
Synopsis of the protocol (for publication) D1_Protocol synopsis_PL_202451747724_blinded 1.0

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-09-27 Poland Acceptable
2024-11-15
2024-11-18
2 NON SUBSTANTIAL MODIFICATION NSM-1 2024-12-30 Poland Acceptable
2024-11-15
2024-12-30
3 SUBSTANTIAL MODIFICATION SM-1 2025-02-03 Poland Acceptable 2025-04-02