Sirolimus & Mycophenolate Mofetil as GvHD Prophylaxis in Myeloablative, Matched Related Donor HCT

Phase 2

Terminated

• Conditions: Leukemia; Acute-graft-versus-host Disease; Non-Hodgkin Lymphoma (NHL); Hodgkin Lymphoma; Hematologic Diseases
• Interventions: Drug: Sirolimus; Drug: Mycophenolate mofetil (MMF); Drug: Carmustine; Drug: FTBI; Drug: Etoposide; Drug: Cyclophosphamide (Cyclo, CY)

• Registration Number: NCT01220297
• Lead Sponsor: Stanford University

Brief Summary

A continuation study of sirolimus and mycophenolate mofetil (MMF) for graft-vs-host disease (GvHD) prophylaxis for patients undergoing matched related allogeneic hematopoietic stem cell transplantation (HSCT) for acute and chronic leukemia, myelodysplastic syndrome (MDS), high risk non-Hodgkin lymphoma (NHL), or Hodgkin lymphoma (HL)

Detailed Description

To explore the novel combination of sirolimus and mycophenolate mofetil (MMF) as graft-vs-host disease (GvHD) prevention in human leukocyte antigen (HLA)-matched related donor peripheral blood stem cell (PBSC) or marrow transplantation (BMT), collectively hematopoietic stem cell transplantation (HSCT). This study will report the toxicities associated with this drug combination.

For all treatments and procedures, Study Day is based on the day of HSCT as Day 0.

Study Timeline

• Study Start: 2006-08
• Study First Submitted: 2009-11-24
• Primary Completion: 2010-08
• Study First Submitted QC: 2010-10-11
• Study First Posted: 2010-10-13
• Study Completion: 2011-08
• Results First Submitted: 2017-03-13
• Status Verified: 2017-05
• Results First Submitted QC: 2017-05-31
• Last Update Submitted: 2017-05-31
• Results First Posted: 2017-06-05
• Last Update Posted: 2017-06-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Carmustine Etoposide Cyclophosphamide	Cyclophosphamide (Cyclo, CY)	Carmustine + Etoposide + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis.
FTBI + Cyclophosphamide	Cyclophosphamide (Cyclo, CY)	FTBI + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis.
Carmustine Etoposide Cyclophosphamide	Mycophenolate mofetil (MMF)	Carmustine + Etoposide + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis.
FTBI + Cyclophosphamide	Mycophenolate mofetil (MMF)	FTBI + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis.
FTBI + Cyclophosphamide	FTBI	FTBI + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis.
Carmustine Etoposide Cyclophosphamide	Sirolimus	Carmustine + Etoposide + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis.
Carmustine Etoposide Cyclophosphamide	Carmustine	Carmustine + Etoposide + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis.
Carmustine Etoposide Cyclophosphamide	Etoposide	Carmustine + Etoposide + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis.
FTBI + Cyclophosphamide	Sirolimus	FTBI + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis.

Primary Outcome Measures

Name	Time	Method
Acute Graft-vs-Host Disease (GvHD) (Grade 2 to 4)	100 days post-transplant	Assessed as the incidence of grade 2 to 4 acute graft-vs-host disease (GvHD) at Day 100 post-transplant.; Stage of Acute GvHD was assessed as follows.; * Stage 1: Skin: rash \< 25% of skin. Liver: bilirubin 2 to 3 mg/dL. Gut: diarrhea \> 500 mL/day or persistent nausea with positive biopsy for GvHD; * Stage 2: Skin: rash 25 to 50% of skin. Liver: bilirubin 3 to 6 mg/dL. Gut: diarrhea \>1000 mL/day.; * Stage 3: Skin: rash \> 50% of skin. Liver: bilirubin 6 to 15 mg/dL. Gut: diarrhea \> 1500 mL/day.; * Stage 4: Skin: generalized erythroderma with bulla formation. Liver: bilirubin \> 15 mg/dL. Gut: severe abdominal pain with or without ileus; Grade of Acute GvHD was determined as follows.; * Grade 1: Stage 1-2 Skin + No Liver stage + No Gut stage; * Grade 2: Stage 3 Skin OR Stage 1 Liver or Stage 1 Gut; * Grade 3: No Skin stage + Stage 2 to 3 Liver Stage 2 to 4 Gut; * Grade 4: Stage 4 Skin + or Stage 2 to 3 Liver + No Gut stage

Secondary Outcome Measures

Name	Time	Method
Acute GvHD (Grade 3 to 4)	100 days post-transplant	Assessed as the incidence of grade 3 to 4 acute GvHD at Day 100 post-transplant.; Stage of Acute GvHD was assessed as follows.; * Stage 1: Skin: rash \< 25% of skin. Liver: bilirubin 2 to 3 mg/dL. Gut: diarrhea \> 500 mL/day or persistent nausea with positive biopsy for GvHD; * Stage 2: Skin: rash 25 to 50% of skin. Liver: bilirubin 3 to 6 mg/dL. Gut: diarrhea \>1000 mL/day.; * Stage 3: Skin: rash \> 50% of skin. Liver: bilirubin 6 to 15 mg/dL. Gut: diarrhea \> 1500 mL/day.; * Stage 4: Skin: generalized erythroderma with bulla formation. Liver: bilirubin \> 15 mg/dL. Gut: severe abdominal pain with or without ileus; Grade of Acute GvHD was determined as follows.; * Grade 1: Stage 1-2 Skin + No Liver stage + No Gut stage; * Grade 2: Stage 3 Skin OR Stage 1 Liver or Stage 1 Gut; * Grade 3: No Skin stage + Stage 2 to 3 Liver Stage 2 to 4 Gut; * Grade 4: Stage 4 Skin + or Stage 2 to 3 Liver + No Gut stage
Disease-free Survival (DFS)	2 years	Assessed as survival without recurrence of disease
Overall Survival	2 years	Overall survival is defined as time from enrollment to time of death or last follow-up, within 2 years.
Veno-occlusive Disease (VoD)	100 days post-transplant	Assessed as the incidence of veno-occlusive disease (VoD) at 100 days post-transplant.

Trial Locations

Locations (1)

Stanford University School of Medicine; 🇺🇸 Stanford, California, United States