Chemokine Receptor CXCR4-DIRECTED Theranostics of Advanced Lymphoproliferative Cancers by Radiopeptide-Based Imaging and Therapy: the Colprit Phase I/Ii Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Klinikum rechts der Isar der TU Muenchen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-517639-35-00

EudraCT number

2022-002989-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Dose response, Safety, Efficacy

Phase I: The definition of the max. tolerated activity by escalation of 90Y-Pentixather in combination with high dose chemotherapy according to SOC (e.g. Melphalan, Treosulfan) followed by autoSCT.
Phase II: to evaluate the overall response rate (ORR) of the treatment regime established in the phase I part of the clinical trial

Secondary objectives 2

1. Phase I: Assessment of the radiation dose received by the patient.
2. Phase II: Median PFS, OS, safety and tolerability, hematopoietic recovery (measured with CBCs)

Conditions and MedDRA coding

Non-Hodgkin lymphomas (NHL)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Histologically proven diagnosis of one of the following active measurable lymphoproliferative malignancies (as defined in chapter 10.1): a) Multiple myeloma (progression after conventional chemotherapy, at least one proteasome inhibitor and one immunomodulatory drug, and high-dose chemotherapy with autoSCT, not currently suitable for allogeneic hematopoietic stem cell transplantation [alloSCT]) b) Aggressive B- and T-NHL including heavily pretreated transformed indolent lymphoma (tNHL) (refractory or relapsed disease after extensive pretreatment with min. 2 regimes, at least one including an anti-CD20 antibody, or after standard high-dose chemotherapy with autoSCT), not currently suitable for alloSCT
2. Inclusion of patients with preceded CAR-T cell therapy is allowed but not a perquisite if such a therapy is not indicated or available at the time point of inclusion
3. Positive 68Ga -Pentixafor PET/CT imaging. In patients with MM 68Ga-Pentixafor-PET/CT may be replaced by 68Ga-Pentixafor-PET/MR
4. Bone marrow aspirate and biopsy (according to clinical routine from last lymphom/myelom specific therapy or 3 - 4 months prior to Baseline) for assessment of pathology, cytology and immunohistochemistry and/or flow cytometry for CXCR4 (CD184) expression
5. Availability of CD34+ peripheral blood hematopoietic stem cells (CD34+ HSC), > 2x106 CD34+HSC / kg body weight) prior to enrolment, obtained during a previous treatment line, including HSC intended for backup use
6. Age ≥ 18 years
7. Eastern cooperative oncology group (ECOG) performance status 0-1 and life expectancy > 3 months and deemed fit for high-dose chemotherapy and autologous stem-cell transplantation
8. Adequate hematopoetic, hepatic (ALAT/ASAT <5x ULN, total Bilirubin <2.5x ULN), renal (CreaCl>40ml/min), cardiac and pulmonary function, excluding organ dysfunctions associated with the underlying disease.
9. Women of childbearing potential (WOCBP) must be non-lactating and surgically sterile or using a highly effective method of birth control and have a negative pregnancy test. Acceptable methods of birth control with a low failure rate (i.e. less than 1% per year) when used consistently and correct are for example implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence (defined as refraining from heterosexual intercourse during the clinical trial) or vasectomized partner. Those contraceptive measures should be applied for 30 days after visit 3 Men with child bearing potential (CBP) must either use a condom, must be vasectomized or stay sexual abstinent. Contraception for WOCBP – as above mentioned – should be considered. Those contraceptive measures should be applied for 90 days after visit 3.
10. Written informed consent

Exclusion criteria 9

1. Evidence of active concurrent malignant disease
2. Evidence of rapid progress of underlying diseases with severely limited life expectancy (< 3 months)
3. Evidence of significant, uncontrolled acute or chronic concomitant diseases that could affect compliance with the protocol or interpretation of results including contraindications against CT-/MRI-/PET-Scans or against myeloablative therapy followed by autoSCT
4. Study participants with discrepant lesions in FDG PET cannot be included
5. Uncontrolled active or chronic infection, including hepatitis B and/or C (Anti-HbS, HbSAG) and HIV (Anti-HIV)
6. Patients with a history of psychiatric illness or condition that could interfere with their ability to understand the requirements of the clinical trial
7. Previous or concurrent participation in another clinical study involving trial medication within the preceding 12 weeks (prior to Baseline) or previous participation in this clinical trial
8. Pregnancy or breast-feeding women
9. Known hypersensitivity to the IMP or NIMP/AxMP or any agent given in association with this clinical trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase I: Determination of maximum tolerated dose (MTD)
2. Phase II: ORR

Secondary endpoints 3

1. Phase I: The dosimetric analysis for the assessment of the radiation dose received by the patient.
2. Phase II: Median PFS, OS, hematopoietic recovery (measured with the time course of CBCs)
3. Safety Endpoints: Frequency and severity of adverse events

Investigational products

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

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Klinikum rechts der Isar der TU Muenchen AöR

Sponsor organisation

Klinikum rechts der Isar der TU Muenchen AöR

Address

Ismaninger Strasse 22, Au-Haidhausen Au-Haidhausen

City

Munich

Postcode

81675

Country

Germany

Scientific contact point

Organisation

Klinikum rechts der Isar der TU Muenchen AöR

Contact name

Dr. Peter Herhaus

Public contact point

Organisation

Klinikum rechts der Isar der TU Muenchen AöR

Contact name

Dr. Peter Herhaus

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

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

Documents 3 files

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

Application history

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