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

NCT01220297 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: IRB-14913SU-09092009-3841BMT209
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

A continuation study of sirolimus and mycophenolate mofetil (MMF) for graft-vs-host disease (GvHD) prophylaxis for patients undergoing matched related allogeneic hematopoietic stem cell transplantation (HSCT) for acute and chronic leukemia, myelodysplastic syndrome (MDS), high risk non-Hodgkin lymphoma (NHL), or Hodgkin lymphoma (HL)

Conditions

Hematologic Diseases; Acute-graft-versus-host Disease; Leukemia; Non-Hodgkin Lymphoma (NHL); Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Acute Graft-vs-Host Disease (GvHD) (Grade 2 to 4)

  Assessed as the incidence of grade 2 to 4 acute graft-vs-host disease (GvHD) at Day 100 post-transplant. Stage of Acute GvHD was assessed as follows. * Stage 1: Skin: rash \< 25% of skin. Liver: bilirubin 2 to 3 mg/dL. Gut: diarrhea \> 500 mL/day or persistent nausea with positive biopsy for GvHD * Stage 2: Skin: rash 25 to 50% of skin. Liver: bilirubin 3 to 6 mg/dL. Gut: diarrhea \>1000 mL/day. * Stage 3: Skin: rash \> 50% of skin. Liver: bilirubin 6 to 15 mg/dL. Gut: diarrhea \> 1500 mL/day. * Stage 4: Skin: generalized erythroderma with bulla formation. Liver: bilirubin \> 15 mg/dL. Gut: severe abdominal pain with or without ileus Grade of Acute GvHD was determined as follows. * Grade 1: Stage 1-2 Skin + No Liver stage + No Gut stage * Grade 2: Stage 3 Skin OR Stage 1 Liver or Stage 1 Gut * Grade 3: No Skin stage + Stage 2 to 3 Liver Stage 2 to 4 Gut * Grade 4: Stage 4 Skin + or Stage 2 to 3 Liver + No Gut stage

  100 days post-transplant

Secondary Outcomes (4)

• Acute GvHD (Grade 3 to 4)

  100 days post-transplant

• Disease-free Survival (DFS)

  2 years

• Overall Survival

  2 years

• Veno-occlusive Disease (VoD)

  100 days post-transplant

Study Arms (2)

Carmustine Etoposide Cyclophosphamide

EXPERIMENTAL

Carmustine + Etoposide + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis.

Drug: Sirolimus; Drug: Mycophenolate mofetil (MMF); Drug: Carmustine; Drug: Etoposide; Drug: Cyclophosphamide (Cyclo, CY)

FTBI + Cyclophosphamide

EXPERIMENTAL

FTBI + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis.

Drug: Sirolimus; Drug: Mycophenolate mofetil (MMF); Drug: Cyclophosphamide (Cyclo, CY); Drug: FTBI

Interventions

Sirolimus DRUG

Immunosuppressant administered orally to: * Adults (age 14 and older), beginning on Day -3 with 12 mg loading dose, followed by 4 mg/day. * Children \< 13 years or weighing 40 kg, beginning on Day -3 with 3 mg/m² loading dose, followed by 1 mg/ m², rounded to the nearest full milligram. Daily dosage may be adjusted to maintain a target serum trough level of 3 to 12 ng/ml. Sirolimus dose tapering will begin at Day 100 in the absence of GvHD, with the goal of discontinuation by 6 months.

Also known as: Rapamycin, Rapamune

Carmustine Etoposide Cyclophosphamide; FTBI + Cyclophosphamide

Mycophenolate mofetil (MMF) DRUG

Immunosuppressant given intravenously (IV) at 15 mg/kg 3 times daily, starting on Day 0 ≥ 2 hr after the completion of the HSCT infusion. Dose of MMF will be based on actual body weight, but limited to 15 kg above ideal body weight. MMF dose tapering will begin at Day 100 in the absence of GvHD, with the goal of discontinuation by 6 months.

Also known as: Cellcept

Carmustine Etoposide Cyclophosphamide; FTBI + Cyclophosphamide

Carmustine DRUG

For Carmustine + Etoposide + Cyclophosphamide cohort, chemotherapy administered IV on Day -6 at the lesser of 15 mg/kg or 550 mg/m².

Also known as: Bis-chloroethylnitrosourea (BCNU, BiCNU)

Carmustine Etoposide Cyclophosphamide

Etoposide DRUG

For Carmustine + Etoposide + Cyclophosphamide cohort, chemotherapy administered IV on Day -4 at 60 mg/kg

Also known as: VP-16, VP16

Carmustine Etoposide Cyclophosphamide

Cyclophosphamide (Cyclo, CY) DRUG

Cyclophosphamide is a chemotherapy agent. For FTBI + Cyclophosphamide cohort, administered IV on Day -3 and -2 at 60 mg/kg. For Carmustine + Etoposide + Cyclophosphamide cohort, administered IV on Day -2 at 100 mg/kg

Also known as: Cytophosphane, Endoxan

Carmustine Etoposide Cyclophosphamide; FTBI + Cyclophosphamide

FTBI DRUG

For FTBI + Cyclophosphamide cohort, administered as 1320 cGy delivered in 11 120 cGy fractions over 4 days starting on Day -7.

Also known as: total body irradiation

FTBI + Cyclophosphamide

Eligibility Criteria

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

You may qualify if:

• Acute myelogenous leukemia (AML), beyond 2nd remission or relapsed/refractory disease, age 2 to 60 years
• AML, in first or subsequent remission or relapsed/refractory disease, age 51 to 60 years of age
• AML with multilineage dysplasia
• Acute lymphoblastic leukemia (ALL), beyond 2nd remission or relapsed/refractory disease, age 2 to 60 years
• ALL, age 51 - 60 years in first or subsequent remission or relapsed/refractory disease
• Chronic myeloid leukemia (CML), beyond 2nd chronic phase or in blast crisis
• Myelodysplastic syndrome (MDS), including World Health Organization (WHO)classifications of refractory anemia with excess blasts-1 (RAEB-1), RAEB-2 and therapy-related MDS
• MDS with poor long-term survival including myeloid metaplasia and myelofibrosis
• Myeloproliferative disorders
• High-risk non-Hodgkin lymphoma (NHL) in 1st emission
• Relapsed or refractory NHL
• Hodgkin lymphoma (HL) beyond first remission
• Males and females of any ethnic background, 2 to 60 years of age
• Karnofsky Performance Status (KPS) ≥ 70% or Lansky performance status \> 70% for patients \< 16 years of age.
• Related, matched-donor identified \[6/6 human leukocyte antigen (HLA)-A, B and DRB1\]

You may not qualify if:

• Prior myeloablative allogeneic or autologous hematopoietic stem cell transplant (HSCT)
• HIV infection
• Pregnant
• Lactating
• Evidence of uncontrolled active infection
• Serum creatinine \> 1.5 mg/dL or 24-hour creatinine clearance \< 50 mL/min
• Direct bilirubin, Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2 x upper limit of normal (ULN)
• Carbon monoxide diffusing capacity (DlCO) \< 60% predicted (adults) OR and in-room air oxygen saturation \< 92% (children)
• Left ventricular ejection fraction \< 45% (adults) OR shortening fraction \< 26%(children)
• Fasting cholesterol \> 300 mg/dL or Triglycerides \> 300 mg/dL while on lipid-lowering agents.
• Receiving investigational drugs unless cleared by the Principal Investigator (PI).
• Prior malignancies except basal cell carcinoma or treated carcinoma in-situ.
• Cancer treated with curative intent ≤ 5 years (EXCEPTION BY PI DISCRETION) (Cancer treated with curative intent \> 5 years will be allowed).

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Hematologic Diseases; Leukemia; Lymphoma, Non-Hodgkin; Hodgkin Disease

Interventions

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

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Neoplasms; 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

Results Point of Contact

• Title: Laura Johnston, MD
• Organization: Stanford Univesity

laura.johnston@stanford.edu

650-723-0822

Study Officials

• Laura Johnston

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: November 24, 2009
• First Posted: October 13, 2010
• Study Start: August 1, 2006
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2011
• Last Updated: June 5, 2017
• Results First Posted: June 5, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)