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

Primary Purpose

Multiple Myeloma, Lymphoma, Acute Myelogenous Leukemia

Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tacrolimus and MMF
Sponsored by
Colorado Blood Cancer Institute
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Lymphoma, Leukemia

Eligibility Criteria

50 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: 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. Age <50 years and eligible for a conventional myeloablative allogeneic SCT. Patients with rapidly progressive intermediate or high- grade NHL, unless in minimal disease state. 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 (see appendix B). Creatinine clearance < 60 ml/min. Patients with hypertension that is poorly controlled on antihypertensive therapy.

Sites / Locations

  • Rocky Mountain Blood and Marrow Transplant ProgramRecruiting

Outcomes

Primary Outcome Measures

The main endpoints are day 100 mortality and acute GVHD.

Secondary Outcome Measures

Full Information

First Posted
March 17, 2006
Last Updated
February 6, 2008
Sponsor
Colorado Blood Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT00304720
Brief Title
Tacrolimus and MMF as Post Grafting Immunosuppression After Conditioning With Flu TBI for HLA Matched Family Donor
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2004
Overall Recruitment Status
Unknown status
Study Start Date
March 2004 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Colorado Blood Cancer Institute

4. Oversight

5. Study Description

Brief Summary
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.
Detailed Description
Conditioning regimen: Days - 4 to -2: Fludarabine 30 mg/m2/day IV. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Lymphoma, Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia, Myelodysplastic Syndrome
Keywords
Lymphoma, Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Tacrolimus and MMF
Primary Outcome Measure Information:
Title
The main endpoints are day 100 mortality and acute GVHD.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: 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. Age <50 years and eligible for a conventional myeloablative allogeneic SCT. Patients with rapidly progressive intermediate or high- grade NHL, unless in minimal disease state. 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 (see appendix B). Creatinine clearance < 60 ml/min. Patients with hypertension that is poorly controlled on antihypertensive therapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter A McSweeney, MD
Organizational Affiliation
Colorado Blood Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rocky Mountain Blood and Marrow Transplant Program
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter A McSweeney, MD
Phone
303-336-2184
Email
Peter.McSweeney@usoncology.com
First Name & Middle Initial & Last Name & Degree
Juli B Murphy
Phone
303-285-5087
Email
Juli.Murphy@usoncology.com
First Name & Middle Initial & Last Name & Degree
Robert M Rifkin, MD
First Name & Middle Initial & Last Name & Degree
Peter A McSweeney, MD
First Name & Middle Initial & Last Name & Degree
Jeffrey V Matous, MD
First Name & Middle Initial & Last Name & Degree
Scott I Bearman, MD
First Name & Middle Initial & Last Name & Degree
Mark W Brunvand, MD
First Name & Middle Initial & Last Name & Degree
Michael B Maris, MD

12. IPD Sharing Statement

Learn more about this trial

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

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