Tacrolimus and MMF as Post Grafting Immunosuppression After Conditioning With Flu TBI for HLA Matched Family Donor

February 6, 2008 updated by: Colorado Blood Cancer Institute

Tacrolimus and Mycophenolate Mofetil as Post-Grafting Immunosuppression After Conditioning With Fludarabine and Low-Dose Total Body Irradiation for Recipients of HLA-Matched Family Donor Hematopoietic Cell Transplants

Primary Objective:

A. To determine whether stable allogeneic hematopoietic engraftment can be safely established in patients receiving a non-myeloablative allogeneic SCT from a matched sibling donor, with fludarabine and low-dose TBI, with pre- and post-transplant immunosuppression with tacrolimus and MMF.

B. To evaluate the incidence of grade II-IV GVHD associated with this treatment.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Conditioning regimen:

  1. Days - 4 to -2: Fludarabine 30 mg/m2/day IV.
  2. Day 0: TBI 2.0 Gy at 6-7 cGy/min from a linear accelerator, followed by stem-cell infusion. TBI will preferably be administered between 7:00 a.m. and 1:00 p.m. to avoid proximity to tacrolimus/MMF administration.

Immunosuppression:

Day -3: Start tacrolimus at 0.06 mg/kg PO BID. Day 0: Start MMF at 15 mg/kg PO b.i.d. from day 0 (PM dose only).

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Denver, Colorado, United States, 80218
        • Recruiting
        • Rocky Mountain Blood and Marrow Transplant Program
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Robert M Rifkin, MD
        • Principal Investigator:
          • Peter A McSweeney, MD
        • Sub-Investigator:
          • Jeffrey V Matous, MD
        • Sub-Investigator:
          • Scott I Bearman, MD
        • Sub-Investigator:
          • Mark W Brunvand, MD
        • Sub-Investigator:
          • Michael B Maris, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients with AML, ALL, CML, CLL, myelodysplastic syndrome (MDS), NHL, Hodgkin's disease (HD), or myeloma, who are at significantly higher than usual risk for mortality from conventional myeloablative allogeneic SCT due to age or comorbidities:

  • Age ³ 50 years with AML or ALL in complete remission or with <10% blasts in bone marrow
  • Age ³ 50 years with MDS or CML.
  • Age > 50 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.

    2. Patients with hematological malignancy relapsed after prior autologous transplantation.

    3. Patients at high-risk (>60%) of relapsing after autologous transplantation for hematological malignancies may receive allogeneic transplant as "consolidative immunotherapy". Diagnoses include multiple myeloma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, AML, ALL and MDS. Minimal duration between autologous and allogeneic transplants is 4 weeks. 4. Patients of any age with hematologic malignancies treatable by allogeneic SCT, who, because of pre-existing medical conditions, are considered to be at significantly increased risk for transplant toxicity using high-dose transplant regimens. 5. Patients with metastatic renal cell carcinoma. Must have include good performance status (Karnofsky score > 60%), no active brain metastases, life expectancy > 6 months, absence of bulky liver metastases. Patients will be treated on other active disease-specific protocols when available. 6. 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. 7. Available HLA-identical sibling donor, or a phenotypically HLA-matched family member. 8. Age < 70 years.

Exclusion Criteria:

  1. 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.
  2. Age <50 years and eligible for a conventional myeloablative allogeneic SCT.
  3. Patients with rapidly progressive intermediate or high- grade NHL, unless in minimal disease state.
  4. Patients with active uncontrolled CNS involvement with malignancy.
  5. Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment.
  6. Females who are pregnant.
  7. Patients who are HIV positive

  8. Organ dysfunction

    1. Left ventricle ejection fraction < 35%.
    2. DLCO <35% of predicted, or receiving continuous supplementary oxygen.
    3. Liver function tests: total bilirubin >2x the upper limit of normal, and/or transaminases >4x the upper limit of normal.
    4. Karnofsky score <50 for patients < 60 years, or <70 for patients aged 60 - 69 years (see appendix B).
    5. Creatinine clearance < 60 ml/min.
    6. Patients with hypertension that is poorly controlled on antihypertensive therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The main endpoints are day 100 mortality and acute GVHD.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Colorado Blood Cancer Institute

Investigators

  • Principal Investigator: Peter A McSweeney, MD, Colorado Blood Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2004

Study Registration Dates

First Submitted

March 17, 2006

First Submitted That Met QC Criteria

March 17, 2006

First Posted (Estimate)

March 20, 2006

Study Record Updates

Last Update Posted (Estimate)

February 8, 2008

Last Update Submitted That Met QC Criteria

February 6, 2008

Last Verified

March 1, 2004

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RMBMT-124-A

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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