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

September 16, 2021 updated by: Laura Johnston, Stanford University

Sirolimus and Mycophenolate Mofetil as GVHD Prophylaxis in Myeloablative, Matched Related Donor Hematopoietic Cell Transplantation

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Regimen Treatment 1
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
Drug: Sirolimus
Immunosuppressant beginning day -3 with 12 mg oral loading dose, 4 mg/day orally for adults
Other Names:
  • rapamycin
Drug: MMF
Immunosuppressant given through IV on day 0 at 15 mg/kg twice daily ≥ 2hr after the completion for the donor cell infusion
Other Names:
  • Mycophenolate Mofetil
Drug: BCNU
15 mg/kg, IV
Other Names:
  • BiCNU
  • Carmustine
Drug: VP-16
60 mg/kg, IV
Other Names:
  • etoposide
Drug: CY
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
Other Names:
  • Endoxan
  • cyclophosphamide
  • cytophosphane
Experimental: Regimen Treatment 2
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
Drug: Sirolimus
Immunosuppressant beginning day -3 with 12 mg oral loading dose, 4 mg/day orally for adults
Other Names:
  • rapamycin
Drug: MMF
Immunosuppressant given through IV on day 0 at 15 mg/kg twice daily ≥ 2hr after the completion for the donor cell infusion
Other Names:
  • Mycophenolate Mofetil
Drug: VP-16
60 mg/kg, IV
Other Names:
  • etoposide
Drug: CY
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
Other Names:
  • Endoxan
  • cyclophosphamide
  • cytophosphane
Drug: FTBI
1320 cGy delivered in 11 120 cGy fractions over 4 day
Other Names:
  • total body irradiation
Experimental: Regimen Treatment 3
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
Drug: Sirolimus
Immunosuppressant beginning day -3 with 12 mg oral loading dose, 4 mg/day orally for adults
Other Names:
  • rapamycin
Drug: MMF
Immunosuppressant given through IV on day 0 at 15 mg/kg twice daily ≥ 2hr after the completion for the donor cell infusion
Other Names:
  • Mycophenolate Mofetil
Drug: VP-16
60 mg/kg, IV
Other Names:
  • etoposide
Drug: CY
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
Other Names:
  • Endoxan
  • cyclophosphamide
  • cytophosphane
Drug: BU
BU 1 mg/kg every 6hr x 4 doses, IV
Other Names:
  • busulfan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To evaluate the incidence of grade II-IV acute GVHD with sirolimus and mycophenolate mofetil GVHD prophylaxis.
Time Frame: D+100 post-transplant
D+100 post-transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Investigators

  • Principal Investigator: Laura Johnston, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2006

Primary Completion (Actual)

August 1, 2007

Study Completion (Actual)

April 1, 2010

Study Registration Dates

First Submitted

July 5, 2006

First Submitted That Met QC Criteria

July 5, 2006

First Posted (Estimate)

July 10, 2006

Study Record Updates

Last Update Posted (Actual)

September 23, 2021

Last Update Submitted That Met QC Criteria

September 16, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-06112
  • 6112 (Other Identifier: Stanford IRB)
  • 97168 (Other Identifier: Stanford University)
  • BMT184 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lymphoma, Non-Hodgkin

Clinical Trials on Sirolimus

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Uzbekistan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe