Tacrolimus and Mycophenolate Mofetil as Post-Grafting Immunosuppression

NCT02178683 | Unknown Phase 3

• 1 other identifier: CBCI-157
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This protocol will evaluate Tacrolimus and MMF after conditioning with fludarabine and low-dose TBI in patients who are not candidates for conventional allografting. A novel approach to immunosuppression will be tested incorporating an early but extended taper of Tacrolimus starting on day +80 or in the case of relapse. The goal is to induce early immunity and GVT effects without compromising GVHD control. The anti-metabolite MMF will be re-introduced on day +100 to try and induce tolerance and block chronic GVHD during the taper of the Tacrolimus. DLI may be given in the presence of disease progression but not for mixed chimerism as in previous protocols.

Conditions

Graft Versus Host Disease

Keywords

TACROLIMUS; MYCOPHENOLATE MOFETIL; FLUDARABINE; HLA-MATCHED; MIS-MATCHED

Outcome Measures

Primary Outcomes (1)

• Engraftment

  To measure safe, stable engraftment using Tacrolimus and Mycophenolate Mofetil as post-grafting immunosuppression in patients following conditioning with fludarabine and total-body irradiation for allogeneic stem cell transplant.

  Post 100 days

Secondary Outcomes (1)

• Graft Versus Host Disease

  Post 100 days

Other Outcomes (1)

• Survival

  Post 100 days

Study Arms (1)

Tacrolimus and Mycophenolate Mofetil

NO INTERVENTION

Non-myeloablative allogeneic SCT from an HLA-Identical or non-identical family onor or unrelated donors, with fludarabine and low-dose TBI, with immunosuppression utilizing tacrolimus and MMF.

Drug: Tacrolimus and MMF.

Interventions

Tacrolimus and MMF. DRUG

First dose of Tacrolimus is given day -4, this continues through day +365. First dose of MMF is given within 4 hours of stem cell infusion, this continues through day +365.

Also known as: Cellcept, MYCOPHENOLATE MOFETIL

Tacrolimus and Mycophenolate Mofetil

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with AML, ALL, CML, CLL, myelodysplastic syndrome (MDS), NHL, Hodgkin's disease (HD), paroxysmal nocturnal hemoglobinuria (PNH), hypoproliferative dysplasia with or without increased blasts, or myeloma, who are at significantly higher than usual risk for mortality from conventional myeloablative allogeneic SCT due to age or comorbidities:
• Age ≥ to 50 years with AML or ALL in complete remission or with \<18% blasts in bone marrow
• Age ≥ to 50 years with MDS or CML.
• Age 16 to 75 years with lymphomas or myeloma, who have failed chemotherapy and are not candidates for an autologous transplant, or who have failed a prior autologous SCT.
• Patients of any age with CLL or low-grade NHL. Patients with CLL and low-grade NHL need to have failed at least first-line treatment, with an alkylating agent, fludarabine or 2-chlorodeoxyadenosine (2-CDA), or anti-CD20 monoclonal antibody rituximab.
• Patients of any age with marrow failure
• Patients ≥60 years old will first be considered for an allogeneic stem cell transplant from a family member and will be offered an unrelated donor transplant only if no suitable family member, preferably an HLA-matched sibling, is available.
• Patients with hematological malignancy relapsed after prior auto transplantation.
• Patients at high-risk (\>60%) of relapsing after autologous transplantation for hematological malignancies may receive allogeneic transplant as "consolidative immunotherapy". Diagnoses include MM, non-HL, HL, AML, ALL and MDS. Minimal duration between auto and allo transplants is 4 weeks.
• Patients of any age with hematologic malignancies treatable by allo SCT, who, because of pre-existing medical conditions or the disease itself (Fanconi anemia or PNH), are considered to be at significantly increased risk for transplant toxicity using high-dose transplantation regimens.
• Patients with metastatic renal cell carcinoma. Must have include good performance status (Karnofsky score ≥ 60%), no active brain metastases, life expectancy of at least 6 months, absence of bulky liver metastases. Patients will be treated on other active disease-specific protocols when available.
• Patients with other malignant diseases treatable with allogeneic SCT may be eligible for this protocol on a case by case basis, if approved by the principal investigator and the BMT attending physicians group.
• Available HLA-identical, a one-antigen mis-matched sibling donor, a phenotypically HLA-matched family member, a phenotypically matched unrelated donor, or a 9/10 matched unrelated donor.
• Age ≤ 75 years.

You may not qualify if:

• Patients with hematological malignancies eligible for a curative autologous SCT: intermediate- or high-grade NHL with chemo-sensitive first relapse.
• HD with chemo-sensitive first relapse.
• Otherwise healthy patients who are eligible for a conventional myeloablative allogeneic SCT.
• Patients with rapidly progressive intermediate or high-grade NHL, unless in minimal disease state after the last treatment.
• Patients with active uncontrolled CNS involvement with malignancy.
• Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment.
• Females who are pregnant.
• Patients who are HIV positive
• Organ dysfunction
• Left ventricle ejection fraction \< 35%.
• DLCO \<35% of predicted, or receiving continuous supplementary oxygen.
• Liver function tests: total bilirubin \>2x the upper limit of normal, and/or transaminases \>4x the upper limit of normal.
• Karnofsky score \<50 for patients \< 60 years, or \<70 for patients aged 60 - 69 years
• Creatinine clearance \< 60 ml/min.
• Patients with hypertension that is poorly controlled on antihypertensive therapy.

Sponsors & Collaborators

• Colorado Blood Cancer Institute: lead

Study Sites (1)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

RECRUITING

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Mark W Brunvand, MD

  Colorado Blood Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Juli Murphy

CONTACT

720-754-4890; Juli.Murphy@healthonecares.com

Nicole Stephens, RN

CONTACT

720-754-4891; Nicole.Stephens@healthonecares.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 16, 2014
• First Posted: July 1, 2014
• Study Start: November 1, 2010
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2018
• Last Updated: July 1, 2014

Record last verified: 2014-06

Locations

US (1)