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

NCT ID: NCT00350181

Last Updated: 2021-09-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-08-31
• Study Completion Date: 2010-04-30

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Sirolimus

Intervention Type: DRUG

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

MMF

Intervention Type: DRUG

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

BCNU

Intervention Type: DRUG

15 mg/kg, IV

VP-16

Intervention Type: DRUG

60 mg/kg, IV

CY

Intervention Type: 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

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

Group Type: EXPERIMENTAL

Sirolimus

Intervention Type: DRUG

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

MMF

Intervention Type: DRUG

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

VP-16

Intervention Type: DRUG

60 mg/kg, IV

CY

Intervention Type: 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

FTBI

Intervention Type: DRUG

1320 cGy delivered in 11 120 cGy fractions over 4 day

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

Group Type: EXPERIMENTAL

Sirolimus

Intervention Type: DRUG

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

MMF

Intervention Type: DRUG

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

VP-16

Intervention Type: DRUG

60 mg/kg, IV

CY

Intervention Type: 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

BU

Intervention Type: DRUG

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

Interventions

Sirolimus

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

Intervention Type: DRUG

MMF

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

BCNU

15 mg/kg, IV

Intervention Type: DRUG

VP-16

60 mg/kg, IV

Intervention Type: 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

Intervention Type: DRUG

FTBI

1320 cGy delivered in 11 120 cGy fractions over 4 day

Intervention Type: DRUG

BU

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

Intervention Type: DRUG

Other Intervention Names

rapamycin; Mycophenolate Mofetil; Carmustine; BiCNU; etoposide; cyclophosphamide; cytophosphane; Endoxan; total body irradiation; busulfan

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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Laura Johnston

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Laura Johnston

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 21552302 (View on PubMed)

Other Identifiers

97168

Identifier Type: OTHER

Identifier Source: secondary_id

BMT184

Identifier Type: OTHER

Identifier Source: secondary_id

6112

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-06112

Identifier Type: -

Identifier Source: org_study_id