A Multi-centre Phase II Trial of GVHD Prophylaxis Following Unrelated Donor Stem Cell Transplantation Comparing Thymoglobulin vs. Calcineurin Inhibitor or Sirolimus-based Post-transplant Cyclophosphamide

Status: Recruiting

Location: See all (15) locations...

Intervention Type: Drug

Study Type: Interventional

Study Phase: Phase 2

SUMMARY

A multi-centre phase II trial of GvHD prophylaxis following unrelated donor stem cell transplantation comparing Thymoglobulin vs. Calcineurin inhibitor or Sirolimus-based post-transplant cyclophosphamide.

Eligibility

Participation Requirements

Sex: All

Minimum Age: 16

Maximum Age: 70

Healthy Volunteers: f

View:

• Availability of suitably matched unrelated donor (9/10 or 10/10)

• Planned to receive one of the following RIC protocols:

‣ Fludarabine-Melphalan (Fludarabine 120-180mg/m2 IV; melphalan ≤ 150mg/m2 IV)

⁃ BEAM or LEAM (carmustine 300mg/m2 IV or lomustine 200mg/m2 IV with: etoposide 800 mg/m2 IV; cytarabine 1600mg/m2 IV; melphalan 140mg/m2 IV)

⁃ Fludarabine-Busulphan (Fludarabine 120-180mg/m2 IV; Busulphan ≤ 8mg/kg PO or 6.4mg/kg IV)

⁃ Fludarabine- Treosulfan (Fludarabine 150mg/m2 IV; Treosulfan 30g/m2 IV)

• Planned use of PBSCs for transplantation

• Planned allo-SCT for one of the following haematological malignancies:

‣ AML in CR (patients enrolled onto the COSI trial are not eligible for this study)

⁃ ALL in CR (patients enrolled onto the ALL-RIC trial are not eligible for this study)

⁃ CMML \<10% blasts

⁃ MDS \<10% blasts (patients enrolled onto the COSI trial are not eligible for this study)

⁃ NHL in CR/PR

⁃ HL in CR/PR

⁃ MM in CR/PR

⁃ CLL in CR/PR

⁃ CML in 1st or 2nd chronic phase

⁃ Myelofibrosis

• Age 16-70 years

• Females of and male patients of reproductive potential (i.e., not post-menopausal or surgically sterilised) must agree to use appropriate, highly effective, contraception from the point of commencing therapy until 12 months after transplant

Locations

Other Locations

United Kingdom

Queen Elizabeth Hospital

RECRUITING

Birmingham

Bristol Haematology and Oncology Centre

RECRUITING

Bristol

Addenbrookes Hospital

RECRUITING

Cambridge

University Hospital of Wales

RECRUITING

Cardiff

Queen Elizabeth Hospital Glasgow

RECRUITING

Glasgow

St Jame's University Hospital

RECRUITING

Leeds

Hammersmith Hospital

RECRUITING

London

King's College Hospital

RECRUITING

London

University College London Hospital

RECRUITING

London

Manchester Royal Infirmary

RECRUITING

Manchester

The Christie

RECRUITING

Manchester

Freeman Hospital

RECRUITING

Newcastle Upon Tyne

Nottingham City Hospital

RECRUITING

Nottingham

Churchill Hospital

RECRUITING

Oxford

Derriford Hospital

RECRUITING

Plymouth

Contact Information

Primary

MoTD Trial

MoTD@trials.bham.ac.uk

0121 371 7859

Backup

Andrea Dr Hodgkinson

A.Hodgkinson@bham.ac.uk

0121 371 4365

Time Frame

Start Date: 2021-02-22

Estimated Completion Date: 2026-01

Participants

Target number of participants: 400

Treatments

Active_comparator: Control Arm Thymoglobulin + Cyclosporine + MMF

Thymoglobulin is given as an intravenous infusion of 2.5 mg/kg/day over 2 days (days -2 and -1; total dose 5 mg/kg) via a central line through a 0.2 micron inline filter. Each dose will be infused over 6-8 hours. No test dose will be given. 30 minutes before Thymoglobulin, the patient should receive methylprednisolone 1mg/kg intravenously, 1g paracetamol PO and 10mg chlorphenamine IV. Patients should be monitored carefully and receive appropriate therapy for any infusion-related or anaphylactic reactions as per local policy.~Patients will receive IV/PO cyclosporine according to local policy to begin on day -1 maintaining a trough level of 100-200 µg/L until day 90 before a subsequent taper in the absence of any active GvHD.~MMF will be given IV/PO according to local policy at a dose of 1g TDS to begin on day -1 and discontinued on day 35 without taper if there is no evidence of active GvHD. In adults weighing \<55kg, MMF should be given at a lower dose of 0.75g IV/PO TDS.

Experimental: Experimental arm (PTCy + Cyclosporine + MMF)

Cyclophosphamide is given as an IV infusion of 50 mg/kg/day over 2 days (days 3 and 4; total dose 100 mg/kg) together with IV hydration and Mesna, as per local policy.~Patients will receive IV/PO cyclosporine according to local policy to begin on day 5 maintaining a trough level of 100-200 µg/L until day 90 before a subsequent taper in the absence of active GvHD.~MMF will be given IV/PO according to local policy at a dose of 1g TDS to begin on day 5 and discontinued on day 35 without taper if there is no evidence of active GvHD. In adults weighing \<55kg, MMF should be given at a lower dose of 0.75g IV/PO TDS.

Experimental: Experimental arm (PTCy + Sirolimus + MMF)

Cyclophosphamide is given as an IV infusion of 50 mg/kg/day over 2 days (days 3 and 4; total dose 100 mg/kg) together with IV hydration and Mesna, as per local policy.~Sirolimus will be initially given PO as a loading dose of 6 mg on day 5 followed by 2 mg daily; doses will be adjusted to maintain a trough level (in whole blood) of 8 to 14 ng/mL until day 60, thereafter 5-8 ng/mL until day 90. In the absence of active GvHD, the dose of sirolimus will be tapered from day 90. We recommend that the daily maintenance dose of sirolimus is reduced empirically to 0.5-1mg daily with concomitant treatment with a triazole anti-fungal agent.~MMF will be given IV/O according to local policy at a dose of 1g TDS to begin on day 5 and discontinued on day 35 without taper if there is no evidence of active GvHD. In adults weighing \<55kg, MMF should be given at a lower dose of 0.75g IV/PO TDS.

Related Therapeutic Areas

Chronic Myelomonocytic Leukemia (CMML)

Myelofibrosis

Hodgkin Lymphoma

Bone Marrow Transplant

Myelodysplastic Syndrome (MDS)

Non-Hodgkin Lymphoma

Acute Lymphoblastic Leukemia (ALL)

Acute Myeloid Leukemia (AML)

Acute Myelomonocytic Leukemia

Chronic Myelogenous Leukemia (CML)

Leukemia

Multiple Myeloma

Similar Clinical Trials

We couldn't find any related articles check for more on the main search page.

View All