GVHD Prophylaxis Regimens for Blood Cancer Stem Cell Transplant

Overseen By Masumi Ueda Oshima

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Research Center

Must not be taking: Antidepressants, others

Disqualifiers: Pregnancy, HIV, Organ dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

150 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase II trial includes a blood stem cell transplant from an unrelated donor to treat blood cancer. The treatment also includes chemotherapy drugs, but in lower doses than conventional (standard) stem cell transplants. The researchers will compare two different drug combinations used to reduce the risk of a common but serious complication called "graft versus host disease" (GVHD) following the transplant. Two drugs, cyclosporine (CSP) and sirolimus (SIR), will be combined with either mycophenolate mofetil (MMF) or post-transplant cyclophosphamide (PTCy). This part of the transplant procedure is the main research focus of the study.

Research Team

Masumi Ueda Oshima

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

Adults aged 18-50 with certain high-risk blood cancers treatable by stem cell transplant from an unrelated donor, but who can't handle high-dose transplants due to medical conditions or prior therapy. Specific criteria include having less than 5% marrow blasts for some leukemias and being in remission for others. Must not be pregnant, breastfeeding, have severe organ dysfunction or active infections unresponsive to treatment.

Inclusion Criteria

My condition is approved by the trial's lead researcher.

I have Waldenstrom's macroglobulinemia and two treatments have not worked for me.

My donor and I mismatch for two HLA class I alleles but match for HLA-DRB1 and HLA-DQ.

Exclusion Criteria

My lymphoma is fast-growing and not low grade.

My blood has at least 5% leukemia cells.

I have high blood pressure that isn't well-controlled despite taking several medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplantation

Patients undergo allogeneic hematopoietic stem cell transplant (HCT) at day 0 with conditioning regimen

1 week

Inpatient stay for transplantation

GVHD Prophylaxis Treatment

Patients receive GVHD prophylaxis with either mycophenolate mofetil, cyclosporine, and sirolimus or cyclosporine, sirolimus, and cyclophosphamide

Up to 52 weeks

Regular follow-up visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Follow-up at 6 months and annually thereafter

Treatment Details

Interventions

• Allogeneic Hematopoietic Stem Cell Transplantation
• Cyclophosphamide
• Cyclosporine
• Mycophenolate Mofetil
• Sirolimus

Trial Overview This phase II trial tests a lower dose of chemotherapy combined with a blood stem cell transplant from an unrelated donor to treat various blood cancers. It compares two drug combinations (CSP+SIR+MMF vs CSP+SIR+PTCy) aiming to reduce graft versus host disease risk after the transplant.

Participant Groups

Group I: Arm II (cyclosporine, sirolimus, cyclophosphamide) Experimental Treatment 4 Interventions

Patients undergo HCT at day 0. Patients with an HLA-matched unrelated donor receive cyclosporine PO BID on days 5-96 then tapered to day 150, sirolimus PO QD on days 5-150 then tapered to day 180, and cyclophosphamide IV on days 3 and 4. Patients with an HLA-mismatched donor receive cyclosporine PO BID on days 5-150 then tapered to day 180, sirolimus PO QD on days 5-180 then tapered to day 365, and cyclophosphamide IV on days 3 and 4.

Group II: Arm I (mycophenolate mofetil, cyclosporine, sirolimus) Experimental Treatment 4 Interventions

Patients undergo allogeneic HCT at day 0. Patients with an HLA-matched unrelated donor receive mycophenolate mofetil PO on days 0 to 40, cyclosporine PO every 12 hours BID on days -3 to 96 then tapered to day 150, and sirolimus PO QD on days -3 to day 150 then tapered to day 180. Patients with an HLA-mismatched donor receive mycophenolate mofetil PO on days 0-100 then tapered to day 150, cyclosporine PO BID on days -3 to 150 then tapered to day 180, and sirolimus PO QD on days -3 to 180 then tapered to day 365.

Allogeneic Hematopoietic Stem Cell Transplantation is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Approved in United States as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Approved in Canada as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Approved in Japan as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+