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

NCT00350181 | Completed Phase 2

• 4 other identifiers: IRB-0611297168BMT1846112
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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

Conditions

Leukemia; Lymphoma, Non-Hodgkin; Hematologic Diseases; Acute GVHD

Outcome Measures

Primary Outcomes (1)

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

  D+100 post-transplant

Study Arms (3)

Regimen Treatment 1

EXPERIMENTAL

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; Drug: MMF; Drug: BCNU; Drug: VP-16; Drug: CY

Regimen Treatment 2

EXPERIMENTAL

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; Drug: MMF; Drug: VP-16; Drug: CY; Drug: FTBI

Regimen Treatment 3

EXPERIMENTAL

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; Drug: MMF; Drug: VP-16; Drug: CY; Drug: BU

Interventions

Sirolimus DRUG

Immunosuppressant beginning day -3 with 12 mg oral loading dose, 4 mg/day orally for adults

Also known as: rapamycin

Regimen Treatment 1; Regimen Treatment 2; Regimen Treatment 3

MMF DRUG

Immunosuppressant given through IV on day 0 at 15 mg/kg twice daily ≥ 2hr after the completion for the donor cell infusion

Also known as: Mycophenolate Mofetil

Regimen Treatment 1; Regimen Treatment 2; Regimen Treatment 3

BCNU DRUG

15 mg/kg, IV

Also known as: Carmustine, BiCNU

Regimen Treatment 1

VP-16 DRUG

60 mg/kg, IV

Also known as: etoposide

Regimen Treatment 1; Regimen Treatment 2; Regimen Treatment 3

CY DRUG

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

Also known as: cyclophosphamide, cytophosphane, Endoxan

Regimen Treatment 1; Regimen Treatment 2; Regimen Treatment 3

FTBI DRUG

1320 cGy delivered in 11 120 cGy fractions over 4 day

Also known as: total body irradiation

Regimen Treatment 2

BU DRUG

BU 1 mg/kg every 6hr x 4 doses, IV

Also known as: busulfan

Regimen Treatment 3

Eligibility Criteria

• Age: 2 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (1)

• 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.

  PMID: 21552302 RESULT

MeSH Terms

Conditions

Leukemia; Lymphoma, Non-Hodgkin; Hematologic Diseases

Interventions

Sirolimus; Mycophenolic Acid; Carmustine; Etoposide; Cyclophosphamide; Whole-Body Irradiation; Busulfan

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemic and Lymphatic Diseases; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Laura Johnston

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: July 5, 2006
• First Posted: July 10, 2006
• Study Start: August 1, 2006
• Primary Completion: August 1, 2007
• Study Completion: April 1, 2010
• Last Updated: September 23, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)