Tests two ways to prevent graft-versus-host disease after donor stem cell transplant

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for people aged 16 to 70 who will have a stem cell transplant from an unrelated donor for a blood cancer or related blood disease. It compares two ways to prevent graft-versus-host disease.

Age

16 to 70 years

Sex

All sexes can join.

Disease stage

Planned stem cell transplant for one of these: AML or ALL in complete remission; CMML or MDS with under 10% blasts; NHL, HL, MM or CLL in complete or partial remission; CML in first or second chronic phase; myelofibrosis.

Earlier treatment

The transplant must use blood stem cells from an unrelated donor with a 9/10 or 10/10 tissue type. Planned conditioning is one of: Fludarabine-Melphalan, BEAM or LEAM, Fludarabine-Busulphan, or Fludarabine-Treosulfan.

Main reasons for not taking part

• Taking part in the COSI or ALL-RIC trials
• Graft manipulation, or alemtuzumab or other T cell depletion not set by the protocol
• Pregnant or breastfeeding women
• Active HBV or HCV infection
• Life expectancy under 8 weeks, or heart, kidney or liver function below the limits set

The registry criteria, word for word

Check if you might fit

Answer for yourself. This is not a decision: only the study team can say whether you can take part.

• Are you between 16 and 70 years old?YesNo

What the trial wants to find out

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.

The 3 groups in the trial

• Control Arm Thymoglobulin + Cyclosporine + MMFExisting treatment, for comparison

  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.

  Treatment: Thymoglobulin, Cyclosporine, and Mycophenolate Mofetil

• Experimental arm (PTCy + Cyclosporine + MMF)Treatment being tested

  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.

  Treatment: Cyclophosphamide, Cyclosporine, and Mycophenolate Mofetil

• Experimental arm (PTCy + Sirolimus + MMF)Treatment being tested

  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.

  Treatment: Cyclophosphamide, Sirolimus, and Mycophenolate Mofetil