Hematologic DiseasesPhase 2NCT01220297
Sirolimus & Mycophenolate Mofetil as GvHD Prophylaxis in Myeloablative, Matched Related Donor HCT
A Phase 2 study testing Sirolimus, Mycophenolate mofetil (MMF) and Carmustine in people with Hematologic Diseases and Acute-graft-versus-host Disease, run by Stanford University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 60 years
- Conditions the study is for
- Hematologic Diseases, Acute-graft-versus-host Disease, Leukemia
- What is being tested?
- Sirolimus, Mycophenolate mofetil (MMF) and Carmustine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2006to Aug 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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]
- Willingness to take oral medications during the transplantation period
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- 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
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- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: Sirolimus and Mycophenolate Mofetil as GvHD Prophylaxis in Myeloablative, Matched Related Donor Hematopoietic Cell Transplantation
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)
Read the detailed description
To explore the novel combination of sirolimus and mycophenolate mofetil (MMF) as graft-vs-host disease (GvHD) prevention in human leukocyte antigen (HLA)-matched related donor peripheral blood stem cell (PBSC) or marrow transplantation (BMT), collectively hematopoietic stem cell transplantation (HSCT). This study will report the toxicities associated with this drug combination.
For all treatments and procedures, Study Day is based on the day of HSCT as Day 0.
- Conditions
- Hematologic Diseases, Acute-graft-versus-host Disease, Leukemia, Non-Hodgkin Lymphoma (NHL), Hodgkin Lymphoma
- Being tested
- Sirolimus, Mycophenolate mofetil (MMF), Carmustine, Etoposide, Cyclophosphamide (Cyclo, CY)
- Medical subject headings
- Hematologic Diseases, Leukemia, Lymphoma, Non-Hodgkin, Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamycin, Rapamune
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.
Mycophenolate mofetil (MMF)Drug
Also called Cellcept
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.
CarmustineDrug
Also called Bis-chloroethylnitrosourea (BCNU, BiCNU)
For Carmustine + Etoposide + Cyclophosphamide cohort, chemotherapy administered IV on Day -6 at the lesser of 15 mg/kg or 550 mg/m².
EtoposideDrug
Also called VP-16, VP16
For Carmustine + Etoposide + Cyclophosphamide cohort, chemotherapy administered IV on Day -4 at 60 mg/kg
Cyclophosphamide (Cyclo, CY)Drug
Also called Cytophosphane, Endoxan
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
FTBIDrug
Also called total body irradiation
For FTBI + Cyclophosphamide cohort, administered as 1320 cGy delivered in 11 120 cGy fractions over 4 days starting on Day -7.
| Study group | Role | What they receive |
|---|---|---|
| Carmustine Etoposide Cyclophosphamide | Experimental | Carmustine + Etoposide + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis. Receives: 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. Receives: Drug: Sirolimus; Drug: Mycophenolate mofetil (MMF); Drug: Cyclophosphamide (Cyclo, CY); Drug: FTBI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 100 days post-transplant
Secondary outcomes (4)
Acute GvHD (Grade 3 to 4)
Assessed as the incidence of grade 3 to 4 acute 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
Measured: 100 days post-transplant
Disease-free Survival (DFS)
Assessed as survival without recurrence of disease
Measured: 2 years
Overall Survival
Overall survival is defined as time from enrollment to time of death or last follow-up, within 2 years.
Measured: 2 years
Veno-occlusive Disease (VoD)
Assessed as the incidence of veno-occlusive disease (VoD) at 100 days post-transplant.
Measured: 100 days post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2010 (estimated)
- Study startAug 2006
- Primary completionAug 2010
- Study completionAug 2011
Why it stopped: Low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hematologic DiseasesStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Laura Johnston, Stanford University
- Investigators
- Laura Johnston, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01220297
- Sponsor's protocol ID
- IRB-14913
- Other IDs
- SU-09092009-3841, BMT209
- Status last verified
- May 2017
- First submitted
- 24 Nov 2009
- Last updated
- 5 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sirolimus and Mycophenolate Mofetil as GvHD Prophylaxis in Myeloablative, Matched Related Donor Hematopoietic Cell Transplantation
- ClinicalTrials.gov ID
- NCT01220297
- Acronym / sponsor ID
- IRB-14913
- Conditions
- Hematologic Diseases, Acute-graft-versus-host Disease, Leukemia, Non-Hodgkin Lymphoma (NHL), Hodgkin Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- Aug 2006
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 13 Oct 2010 (estimated)
- Results
- Posted 5 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Detailed description
To explore the novel combination of sirolimus and mycophenolate mofetil (MMF) as graft-vs-host disease (GvHD) prevention in human leukocyte antigen (HLA)-matched related donor peripheral blood stem cell (PBSC) or marrow transplantation (BMT), collectively hematopoietic stem cell transplantation (HSCT). This study will report the toxicities associated with this drug combination.
For all treatments and procedures, Study Day is based on the day of HSCT as Day 0.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Carmustine Etoposide Cyclophosphamide | Experimental | Drug: Sirolimus, Drug: Mycophenolate mofetil (MMF), Drug: Carmustine, Drug: Etoposide, Drug: Cyclophosphamide (Cyclo, CY)Carmustine + Etoposide + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis. |
| FTBI + Cyclophosphamide | Experimental | Drug: Sirolimus, Drug: Mycophenolate mofetil (MMF), Drug: Cyclophosphamide (Cyclo, CY), Drug: FTBIFTBI + Cyclophosphamide followed by Sirolimus and Mycophenolate mofetil (MMF) as prophylaxis. |
Who may qualify
- Ages
- 2 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (17 listed)
- 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
Key exclusion criteria (13 listed)
- Prior myeloablative allogeneic or autologous hematopoietic stem cell transplant (HSCT)
- HIV infection
- Pregnant
- Lactating
- Evidence of uncontrolled active infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirolimusAlso: Rapamycin, RapamuneImmunosuppressant 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. | Drug | Carmustine Etoposide Cyclophosphamide, FTBI + Cyclophosphamide |
| Mycophenolate mofetil (MMF)Also: CellceptImmunosuppressant 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. | Drug | Carmustine Etoposide Cyclophosphamide, FTBI + Cyclophosphamide |
| CarmustineAlso: Bis-chloroethylnitrosourea (BCNU, BiCNU)For Carmustine + Etoposide + Cyclophosphamide cohort, chemotherapy administered IV on Day -6 at the lesser of 15 mg/kg or 550 mg/m². | Drug | Carmustine Etoposide Cyclophosphamide |
| EtoposideAlso: VP-16, VP16For Carmustine + Etoposide + Cyclophosphamide cohort, chemotherapy administered IV on Day -4 at 60 mg/kg | Drug | Carmustine Etoposide Cyclophosphamide |
| Cyclophosphamide (Cyclo, CY)Also: Cytophosphane, EndoxanCyclophosphamide 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 | Drug | Carmustine Etoposide Cyclophosphamide, FTBI + Cyclophosphamide |
| FTBIAlso: total body irradiationFor FTBI + Cyclophosphamide cohort, administered as 1320 cGy delivered in 11 120 cGy fractions over 4 days starting on Day -7. | Drug | FTBI + Cyclophosphamide |
Primary outcome
Acute Graft-vs-Host Disease (GvHD) (Grade 2 to 4)
Time frame: 100 days post-transplant
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
4 secondary outcomes
Acute GvHD (Grade 3 to 4)
Time frame: 100 days post-transplant
Disease-free Survival (DFS)
Time frame: 2 years
Overall Survival
Time frame: 2 years
Veno-occlusive Disease (VoD)
Time frame: 100 days post-transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laura Johnston principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sirolimus, Mycophenolate mofetil (MMF) and Carmustine in people with Hematologic Diseases and Acute-graft-versus-host Disease, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute Graft-vs-Host Disease (GvHD) (Grade 2 to 4) (time frame: 100 days post-transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2017.