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

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ClinicalTrials.gov Identifier: NCT00350181
Recruitment Status : Completed
First Posted : July 10, 2006
Last Update Posted : September 23, 2021
Sponsor:
Information provided by (Responsible Party):
Laura Johnston, Stanford University

Study Description
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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

Condition or disease Intervention/treatment Phase
Leukemia Lymphoma, Non-Hodgkin Hematologic Diseases Acute GVHD Drug: Sirolimus Drug: MMF Drug: BCNU Drug: VP-16 Drug: CY Drug: FTBI Drug: BU Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Sirolimus and Mycophenolate Mofetil as GVHD Prophylaxis in Myeloablative, Matched Related Donor Hematopoietic Cell Transplantation
Study Start Date : August 2006
Actual Primary Completion Date : August 2007
Actual Study Completion Date : April 2010

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: Mycophenolate Mofetil

Drug: BCNU
15 mg/kg, IV
Other Names:
  • Carmustine
  • BiCNU

Drug: VP-16
60 mg/kg, IV
Other Name: 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:
  • cyclophosphamide
  • cytophosphane
  • Endoxan
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 Name: 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 Name: Mycophenolate Mofetil

Drug: VP-16
60 mg/kg, IV
Other Name: 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:
  • cyclophosphamide
  • cytophosphane
  • Endoxan

Drug: FTBI
1320 cGy delivered in 11 120 cGy fractions over 4 day
Other Name: 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 Name: 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 Name: Mycophenolate Mofetil

Drug: VP-16
60 mg/kg, IV
Other Name: 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:
  • cyclophosphamide
  • cytophosphane
  • Endoxan

Drug: BU
BU 1 mg/kg every 6hr x 4 doses, IV
Other Name: busulfan


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

Eligibility Criteria
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Ages Eligible for Study:   2 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00350181


Locations
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United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
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Principal Investigator: Laura Johnston Stanford University
More Information
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Publications of Results:

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Responsible Party: Laura Johnston, Associate Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00350181    
Other Study ID Numbers: IRB-06112
97168 ( Other Identifier: Stanford University )
BMT184 ( Other Identifier: OnCore )
6112 ( Other Identifier: Stanford IRB )
First Posted: July 10, 2006    Key Record Dates
Last Update Posted: September 23, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Lymphoma, Non-Hodgkin
Hematologic Diseases
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Mycophenolic Acid
Sirolimus
Cyclophosphamide
Busulfan
Carmustine
Etoposide
 Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antibiotics, Antineoplastic
Antibiotics, Antitubercular