CN160: Ruxolitinib Therapy in Children after Bone Marrow Transplant

Brief Summary

This phase 2 clinical trial evaluates whether substituting ruxolitinib for cyclosporine A after allogeneic transplant will reduce the incidence of graft-vs.-host disease (GVHD) for patients with lymphoid- or myeloid-based cancers.

Our hypothesis is it may be possible to safely stop calcineurin inhibitors on day +60 post allogeneic hematopoietic cell transplantation by adding ruxolitinib on days +40–100 after engraftment. This may decrease the incidence of severe, acute GVHD within the first 100 days post-transplant while reducing toxicity from prolonged use of calcineurin inhibitors.

This trial will only use bone marrow donors. Human leukocyte antigen (HLA)-identical sibling donors will be considered first, followed by histocompatible relatives or unrelated donors matched at 12 of 12 HLA alleles.

There will be 2 preparative regimens:

• For hematological malignancies of the lymphoid lineage, we will use total body irradiation and cyclophosphamide unless total body irradiation is contraindicated.
• For myeloid malignancies, we will use thiotepa, busulfan, and fludarabine. This regimen was associated with a reduced risk of relapse and a trend for improved survival with comparable non-relapse mortality compared to busulfan and cyclophosphamide, our current regimen.

All transplant recipients will receive cyclosporine along with methotrexate and ruxolitinib as GVHD prophylaxis. Recipients of matched unrelated donor transplants will receive rabbit anti-thymocyte globulin for additional immunosuppression. This is standard for unrelated donor transplants.

Primary objective

Estimate the incidence of severe acute GVHD using a prophylaxis regimen with no calcineurin inhibitors after day +60 post first allogeneic matched-sibling or unrelated-donor transplant for hematological malignancies.

Secondary objective

Determine the cumulative incidence of relapse, non-relapse mortality, chronic GVHD, and overall survival in study participants 1 year after transplant.

Eligibility criteria include:

• A high-risk hematologic malignancy that requires a bone marrow transplant
• Ages 12–21 years
• A related or unrelated donor matched at 12 of 12 HLA alleles
• Karnofsky/Lansky score of 70 or higher
• Free of severe infection
• Adequate heart, liver, kidney, and lung function
• Not pregnant

Exclusion criteria include patients who:

• Had a peripheral blood, stem cells as a graft source, or underwent a prior hematopoietic cell transplant
• Have a non-permissive mismatch at the DPB1 allele
• Are positive for HIV, hepatitis B surface antigen (HBsAg), or hepatitis C
• Have latent tuberculosis with positive TB IFN gamma release assay

Study site

St. Jude Children’s Research Hospital, Memphis, TN

About this study

When you get a transplant, the transplanted cells from another person’s body (donor cells) see your body as different, and they try to fight your body. As these donor cells fight your body, you may get symptoms that make you quite sick. These symptoms are known as graft-versus-host disease (GVHD). GVHD symptoms can happen almost anywhere in your body. They can happen right away or later. To decrease the chance of getting GVHD, doctors usually give patients drugs called cyclosporine A (CsA) until 100 days after the transplant, and methotrexate.

CsA has many side effects that increase the risk of complications. CsA also affects how donor lymphocytes kill leukemia cells. We hope to add a new drug called ruxolitinib to therapy after transplant. The use of this drug would lower the amount of CsA you receive. The FDA has approved ruxolitinib for the treatment of bad cases of GVHD.

Instead of giving CsA until 100 days after transplant, doctors would like to give it until only 60 days after transplant. They will add ruxolitinib beginning the 40th day after transplant and continue giving it until the 100th day.

Ruxolitinib works differently than CsA, and patients tolerate it well. It does not affect how donor lymphocytes kill leukemia cells. We will test the combination of CsA with methotrexate and ruxolitinib to see if GVHD symptoms decrease.

Purpose of this clinical trial

The main purpose of this study is to find out if it is safe to stop CsA early and use a new drug called ruxolitinib instead.

Eligibility overview

• A high-risk hematologic malignancy that requires a bone marrow transplant
• Ages 12–21 years
• A related or unrelated donor
• Free of severe infection
• Adequate heart, liver, kidney, and lung function
• Not pregnant