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

Primary Purpose

Leukemia, Lymphoma, Non-Hodgkin, Hematologic Diseases

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sirolimus
MMF
BCNU
VP-16
CY
FTBI
BU
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia

Eligibility Criteria

2 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Disease Categories: (one of the following) AML, age 2 - 60 years beyond 2nd remission or relapsed/refractory disease AML, age 51-60 years of age, in first or subsequent remission or relapsed/refractory disease AML with multilineage dysplasia ALL, age 2 - 60 years beyond 2nd remission or relapsed/refractory disease ALL, age 51 - 60 years in first or subsequent remission or relapsed/refractory disease CML Beyond 2nd chronic phase or in blast crisis MDS; Includes World Health Organization classifications of refractory anemia with excess blasts-1 (RAEB-1), RAEB-2 and therapy-related MDS Myeloproliferative disorders; MDS with poor long-term survival including myeloid metaplasia and myelofibrosis High risk NHL in first remission Relapsed or refractory NHL HL beyond first remission Males and females of any ethnic background 2 - 60 years of age Karnofsky Performance Status ≥ 70% or Lansky performance status > 70% for patients < 16 years of age. Matched related donor identified: 6/6 HLA-A, B and DRB1 Willingness to take oral medications during the transplantation period Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Prior myeloablative allogeneic or autologous HCT HIV infection Pregnant Lactating females Evidence of uncontrolled active infection Organ Dysfunction: Serum creatinine > 1.5 mg/dL or 24 hour creatinine clearance < 50 ml/min Direct bilirubin, ALT or AST > 2 x ULN In adults DLCO < 60% predicted and in children room air oxygen saturation < 92% In adults, left ventricular ejection fraction < 45% and in children, shortening fraction < 26% Fasting Cholesterol > 300 mg/dL or Triglycerides > 300 mg/dL while on lipid-lowering agents. Patients receiving investigational drugs unless cleared by the PI. Patients with prior malignancies except basal cell carcinoma or treated carcinoma in-situ. Cancer treated with curative intent > 5 years will be allowed. Cancer treated with curative intent ≤ 5 years will not be allowed with PI approval.

Sites / Locations

  • Stanford University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Regimen Treatment 1

Regimen Treatment 2

Regimen Treatment 3

Arm Description

For subjects 18-60 years old with lymphoma: (BCNU+ VP-16 +CY) BCNU 15 mg / kg (maximum dose 550 mg/m² actual body weight) on day -6. VP 60 mg / kg on day 4 and CY 100 mg / kg on day -2. Followed by Sirolimus and MMF as prophylaxis

For subjects 18-50 years old with AML, ALL or CML: (VP-16 +CY+ FBI) Patients aged 18-50 years with AML, ALL or CML: FTBI 1320 cGy delivered in 11 120 cGy fractions over 4 days on days -8 through -5. VP 60 mg / kg on day -4 and CY 60 mg / kg on day -2. Followed by Sirolimus and MMF as prophylaxis

For subjects 51-60 years with MDS, AML or ALL or 18-60 with MDS, secondary AML pr non-CML myeloproliferative disease: (BU+ VP-16 +CY) BU 1 mg/kg every 6 hours X 14 doses on days -9 through -6 with target concentration at steady state of X 800 ng / ml based on first dose pharmacokinetics. VP 60 mg / kg on day -5 and CY 45 mg / kg per day -2 days on day -3 and day -2. Followed by Sirolimus and MMF as prophylaxis

Outcomes

Primary Outcome Measures

To evaluate the incidence of grade II-IV acute GVHD with sirolimus and mycophenolate mofetil GVHD prophylaxis.

Secondary Outcome Measures

Full Information

First Posted
July 5, 2006
Last Updated
September 16, 2021
Sponsor
Stanford University
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1. Study Identification

Unique Protocol Identification Number
NCT00350181
Brief Title
Sirolimus & Mycophenolate Mofetil as GVHD Prophylaxis in Myeloablative, Matched Related Donor HCT
Official Title
Sirolimus and Mycophenolate Mofetil as GVHD Prophylaxis in Myeloablative, Matched Related Donor Hematopoietic Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
August 2006 (undefined)
Primary Completion Date
August 2007 (Actual)
Study Completion Date
April 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
GVHD prophylaxis of sirolimus and mycophenolate mofetil for patients undergoing matched related allogeneic transplant for acute and chronic leukemia, MDS, high risk NHL and HL
Detailed Description
To explore the novel combination of sirolimus and mycophenolate mofetil (MMF) as graft versus host disease (GVHD) prevention in HLA matched related donor blood or marrow transplantation (BMT). This study will report the toxicities associated with this drug combination and also explore possible correlations between specific blood cell types and antibody production during this therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma, Non-Hodgkin, Hematologic Diseases, Acute GVHD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Regimen Treatment 1
Arm Type
Experimental
Arm Description
For subjects 18-60 years old with lymphoma: (BCNU+ VP-16 +CY) BCNU 15 mg / kg (maximum dose 550 mg/m² actual body weight) on day -6. VP 60 mg / kg on day 4 and CY 100 mg / kg on day -2. Followed by Sirolimus and MMF as prophylaxis
Arm Title
Regimen Treatment 2
Arm Type
Experimental
Arm Description
For subjects 18-50 years old with AML, ALL or CML: (VP-16 +CY+ FBI) Patients aged 18-50 years with AML, ALL or CML: FTBI 1320 cGy delivered in 11 120 cGy fractions over 4 days on days -8 through -5. VP 60 mg / kg on day -4 and CY 60 mg / kg on day -2. Followed by Sirolimus and MMF as prophylaxis
Arm Title
Regimen Treatment 3
Arm Type
Experimental
Arm Description
For subjects 51-60 years with MDS, AML or ALL or 18-60 with MDS, secondary AML pr non-CML myeloproliferative disease: (BU+ VP-16 +CY) BU 1 mg/kg every 6 hours X 14 doses on days -9 through -6 with target concentration at steady state of X 800 ng / ml based on first dose pharmacokinetics. VP 60 mg / kg on day -5 and CY 45 mg / kg per day -2 days on day -3 and day -2. Followed by Sirolimus and MMF as prophylaxis
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Other Intervention Name(s)
rapamycin
Intervention Description
Immunosuppressant beginning day -3 with 12 mg oral loading dose, 4 mg/day orally for adults
Intervention Type
Drug
Intervention Name(s)
MMF
Other Intervention Name(s)
Mycophenolate Mofetil
Intervention Description
Immunosuppressant given through IV on day 0 at 15 mg/kg twice daily ≥ 2hr after the completion for the donor cell infusion
Intervention Type
Drug
Intervention Name(s)
BCNU
Other Intervention Name(s)
Carmustine, BiCNU
Intervention Description
15 mg/kg, IV
Intervention Type
Drug
Intervention Name(s)
VP-16
Other Intervention Name(s)
etoposide
Intervention Description
60 mg/kg, IV
Intervention Type
Drug
Intervention Name(s)
CY
Other Intervention Name(s)
cyclophosphamide, cytophosphane, Endoxan
Intervention Description
For subjects aged 18-60 with lymphoma 100 mg/kg, IV For subjects aged with AML, ALL or CML 18-50 60 mg/kg, IV For subjects aged 51-60 with MDS, AML or ALL or patients age 18-60 with MDS, secondary AML or non-CML myeloproliferative disease 45 mg/kg
Intervention Type
Drug
Intervention Name(s)
FTBI
Other Intervention Name(s)
total body irradiation
Intervention Description
1320 cGy delivered in 11 120 cGy fractions over 4 day
Intervention Type
Drug
Intervention Name(s)
BU
Other Intervention Name(s)
busulfan
Intervention Description
BU 1 mg/kg every 6hr x 4 doses, IV
Primary Outcome Measure Information:
Title
To evaluate the incidence of grade II-IV acute GVHD with sirolimus and mycophenolate mofetil GVHD prophylaxis.
Time Frame
D+100 post-transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Disease Categories: (one of the following) AML, age 2 - 60 years beyond 2nd remission or relapsed/refractory disease AML, age 51-60 years of age, in first or subsequent remission or relapsed/refractory disease AML with multilineage dysplasia ALL, age 2 - 60 years beyond 2nd remission or relapsed/refractory disease ALL, age 51 - 60 years in first or subsequent remission or relapsed/refractory disease CML Beyond 2nd chronic phase or in blast crisis MDS; Includes World Health Organization classifications of refractory anemia with excess blasts-1 (RAEB-1), RAEB-2 and therapy-related MDS Myeloproliferative disorders; MDS with poor long-term survival including myeloid metaplasia and myelofibrosis High risk NHL in first remission Relapsed or refractory NHL HL beyond first remission Males and females of any ethnic background 2 - 60 years of age Karnofsky Performance Status ≥ 70% or Lansky performance status > 70% for patients < 16 years of age. Matched related donor identified: 6/6 HLA-A, B and DRB1 Willingness to take oral medications during the transplantation period Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Prior myeloablative allogeneic or autologous HCT HIV infection Pregnant Lactating females Evidence of uncontrolled active infection Organ Dysfunction: Serum creatinine > 1.5 mg/dL or 24 hour creatinine clearance < 50 ml/min Direct bilirubin, ALT or AST > 2 x ULN In adults DLCO < 60% predicted and in children room air oxygen saturation < 92% In adults, left ventricular ejection fraction < 45% and in children, shortening fraction < 26% Fasting Cholesterol > 300 mg/dL or Triglycerides > 300 mg/dL while on lipid-lowering agents. Patients receiving investigational drugs unless cleared by the PI. Patients with prior malignancies except basal cell carcinoma or treated carcinoma in-situ. Cancer treated with curative intent > 5 years will be allowed. Cancer treated with curative intent ≤ 5 years will not be allowed with PI approval.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Laura Johnston
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21552302
Citation
Johnston L, Florek M, Armstrong R, McCune JS, Arai S, Brown J, Laport G, Lowsky R, Miklos D, Shizuru J, Sheehan K, Lavori P, Negrin R. Sirolimus and mycophenolate mofetil as GVHD prophylaxis in myeloablative, matched-related donor hematopoietic cell transplantation. Bone Marrow Transplant. 2012 Apr;47(4):581-8. doi: 10.1038/bmt.2011.104. Epub 2011 May 9.
Results Reference
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Sirolimus & Mycophenolate Mofetil as GVHD Prophylaxis in Myeloablative, Matched Related Donor HCT

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