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Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation of Patients With Hematological Diseases

Primary Purpose

Hematologic Malignancy

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ANTI-CD45
CAMPATH-1H
FK506
Fludarabine
Total Body Irradiation
Stem cell infusion
Sponsored by
Baylor College of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematologic Malignancy focused on measuring Acute myeloid leukemia, Acute lymphoblastic leukemia, Chronic myeloid leukemia, Non-Hodgkin's lymphoma, Hodgkin's disease, Myelodysplastic syndrome, Myeloproliferative disorders, Multiple myeloma, Severe aplastic anemia

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients with one of the following high risk diseases needing allogeneic hemopoietic stem cell transplantation: Acute myeloid leukemia either a) Primary refractory, or b) Beyond first complete remission(CR1), or c) In CR1 with high risk of relapse Acute lymphoblastic leukemia either a) Primary refractory, or b) Beyond first complete remission(CR1), or c) In CR1 with high risk of relapse Chronic myeloid leukemia, either a) Accelerated phase, or b) Blast crisis, or c) Chronic phase and not achieving major cytogenetic response despite standard therapy Chronic lymphocytic leukemia, either a) Primary refractory, or b) Beyond first complete remission(CR1), Non Hodgkin's lymphoma, either a) Primary refractory, or b) Beyond first complete remission(CR1) Hodgkin's disease, either a) Primary refractory, or b) Beyond first complete remission(CR1), Myelodysplastic syndrome with IPSS score > 0. (Appendix A) Myeloproliferative disorders (with the exclusion of chronic myeloid leukemia) a) Primary Myelofibrosis with Lile score of 1 or 2 (Appendix B) b) Polycythemia Vera or Essential Thrombocythemia transformed to AML or Myelofibrosis and PV "spent phase" Multiple Myeloma with stage II or III disease Severe aplastic anemia Conditions that increase Treatment Related Mortality (need one or more to be eligible): Greater or equal to 35 years of age; Ejection Fraction of less than 50%; DLCO less than 50% or FEV1/FVC < 80% of predicted value; Diabetes Mellitus; Renal insufficiency (serum creatinine abnormal); Hepatic dysfunction-transaminases, or alkaline phosphatase, or bilirubin twice the upper limit of normal; Prior recent history of systemic fungal infection; Multiple prior treatment regimens (equal to or more than 3); Significant Grade III or IV neurologic, cardiac, pulmonary, renal or hepatic toxicity from previous treatment; Prior Autologous or Allogeneic Stem Cell transplantation; Available Healthy Donor without any contraindications for donation. 5/6 or 6/6 related or unrelated donor (molecular typing for DRB1); Patient and/or responsible person able to understand and sign consent Exclusion Criteria: Pregnant and lactating women, or women unwilling to use contraception. HIV positive patient Unstable angina and uncompensated congestive heart failure (Zubrod of 3 or greater) Severe chronic pulmonary disease requiring oxygen (Zubrod of 3 or greater) Child's class C cirrhosis Unstable cerebral vascular disease or recent hemorrhagic stroke (less than 6 months) Patients with known allergy to rat serum products

Sites / Locations

  • Texas Children's Hospital
  • The Methodist Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

1

2

Arm Description

recipients of HLA matched sibling transplants

recipients of unrelated or mismatched family donor transplants

Outcomes

Primary Outcome Measures

Assess safety and feasibility of monoclonal abs directed to CD45 and CD52 antigens, Fludarabine and low dose TBI, as a non-myeloablative preparatory regimen for allo HSCT. This will be determined by 100d Non-relapse mortality and 100d Graft rejection

Secondary Outcome Measures

To obtain a preliminary estimate of the efficacy of this therapy as defined by: Complete remission at day 100 and One-year disease free survival.

Full Information

First Posted
March 26, 2003
Last Updated
June 27, 2012
Sponsor
Baylor College of Medicine
Collaborators
The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT00056966
Brief Title
Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation of Patients With Hematological Diseases
Official Title
Phase I/II Study of CD45 Antibodies and Alemtuzumab Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation of Patients With Hematological Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
June 2012
Overall Recruitment Status
Completed
Study Start Date
November 2002 (undefined)
Primary Completion Date
May 2005 (Actual)
Study Completion Date
December 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Baylor College of Medicine
Collaborators
The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Participants in this study have a hematologic malignancy (a disorder in the bone marrow that affects the body's ability to create blood) that might benefit from receiving an allogeneic stem cell transplant (meaning the cells come from a donor) from a family member or nearly identical matched donor. The donor may either be a matched sibling, a mismatched family member, or an unrelated person. Usually these patients are given high doses of chemotherapy before receiving a stem cell transplant to keep their immune system from rejecting the donor stem cells and to kill any diseased cells that remain in the body. However, this group of patients have a high risk of developing possibly life-threatening treatment-related side effects such as infections, damage to vital organs such as lungs, liver, kidney and heart, as well as graft versus host disease (GVHD). Instead of the high dose chemotherapy and radiotherapy usually given before a transplant, this research study uses a new pre-transplant combination of three drugs, Fludarabine, Anti-CD45 and CAMPATH-1H with low dose radiotherapy. Fludarabine is a chemotherapy drug while Anti-CD45 and CAMPATH-1H are antibodies against certain types of blood cells, including those which are causing this disease. CAMPATH-1H is particularly important because it stays active in the body for a long time after it is given, which means it may work longer to prevent GVHD symptoms. Anti-CD45 may help in eradicating residual malignant cells. All these agents also help in preventing rejection of donor stem cells. This study is designed to give a less intense chemotherapy and radiotherapy, so that the life-threatening toxicities of conventional high dose chemotherapy and radiotherapy regimen can be reduced, while maintaining the ability to cure cancer.
Detailed Description
CAMPATH-1H will be given as a daily IV infusion for three days. Fludarabine will be given as a daily IV infusion for four days. Anti-CD45 will be given as a daily IV infusion for 4 days. Patients will then receive radiotherapy (also known as Total Body Irradiation or TBI) for one day. A summary of the treatment follows: Day - 8: CAMPATH-1H and Fludarabine Day - 7: CAMPATH-1H and Fludarabine Day - 6: CAMPATH-1H and Fludarabine Day - 5: Anti-CD45 and Fludarabine Day - 4: Anti-CD45 Day - 3: Anti-CD45 Day - 2: Anti-CD45 Day - 1: TBI Day 0: Stem Cell Infusion (transplant) To help prevent the body from developing GVHD, patients will also receive the drug FK506, starting two days before the transplant and continuing for at least one month. Both the CAMPATH-1H and the Anti-CD45 can cause allergic reactions so patients will be given drugs to help prevent those reactions before receiving daily doses. To see how CAMPATH-1H works in patients with hematologic malignancies, some patients will be asked to participate in pharmacokinetic studies. For this, approximately 13 blood samples will be taken from the central line scheduled before each infusion on Day -8 to Day -6, daily thereafter until Day 0, and then approximately once per week on days 7, 14, 21 and 28 post transplant. No more than 5 teaspoonfuls total will be drawn. To see how Anti-CD45 works in patients with hematologic malignancies some patients will be asked to participate in pharmacokinetic studies. Approximately 22 blood samples will be taken from the central line scheduled before, during and after each infusion and after the end of the last infusion of Anti-CD45. No more than 10 teaspoonfuls total will be drawn over the course of the four anti-CD45 infusions.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Malignancy
Keywords
Acute myeloid leukemia, Acute lymphoblastic leukemia, Chronic myeloid leukemia, Non-Hodgkin's lymphoma, Hodgkin's disease, Myelodysplastic syndrome, Myeloproliferative disorders, Multiple myeloma, Severe aplastic anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
recipients of HLA matched sibling transplants
Arm Title
2
Arm Type
Experimental
Arm Description
recipients of unrelated or mismatched family donor transplants
Intervention Type
Drug
Intervention Name(s)
ANTI-CD45
Intervention Description
400ug/kg Day-5 through Day-2
Intervention Type
Drug
Intervention Name(s)
CAMPATH-1H
Other Intervention Name(s)
anti-CD52, alemtuzumab
Intervention Description
Day -8 through Day -6 Dosed per Institutional SOP
Intervention Type
Drug
Intervention Name(s)
FK506
Other Intervention Name(s)
tacrolimus
Intervention Description
Day -2 through Day 30 dose adjusted to maintain level between 5-15 ng/ml.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Day-8 through Day-5 30 mg/m2
Intervention Type
Radiation
Intervention Name(s)
Total Body Irradiation
Intervention Description
Day-1 single dose 450 cGy
Intervention Type
Procedure
Intervention Name(s)
Stem cell infusion
Intervention Description
Patients will receive peripheral blood stem cells from a HLA matched or one antigen mismatched related or unrelated donor (target CD34+ cell count >2 x 106/kg). When peripheral stem cells are unavailable or insufficient, bone marrow (target mononuclear cell count >2 x 108/kg) will be substituted.
Primary Outcome Measure Information:
Title
Assess safety and feasibility of monoclonal abs directed to CD45 and CD52 antigens, Fludarabine and low dose TBI, as a non-myeloablative preparatory regimen for allo HSCT. This will be determined by 100d Non-relapse mortality and 100d Graft rejection
Time Frame
100 days post transplant
Secondary Outcome Measure Information:
Title
To obtain a preliminary estimate of the efficacy of this therapy as defined by: Complete remission at day 100 and One-year disease free survival.
Time Frame
100 days and 1 year post transplant

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with one of the following high risk diseases needing allogeneic hemopoietic stem cell transplantation: Acute myeloid leukemia either a) Primary refractory, or b) Beyond first complete remission(CR1), or c) In CR1 with high risk of relapse Acute lymphoblastic leukemia either a) Primary refractory, or b) Beyond first complete remission(CR1), or c) In CR1 with high risk of relapse Chronic myeloid leukemia, either a) Accelerated phase, or b) Blast crisis, or c) Chronic phase and not achieving major cytogenetic response despite standard therapy Chronic lymphocytic leukemia, either a) Primary refractory, or b) Beyond first complete remission(CR1), Non Hodgkin's lymphoma, either a) Primary refractory, or b) Beyond first complete remission(CR1) Hodgkin's disease, either a) Primary refractory, or b) Beyond first complete remission(CR1), Myelodysplastic syndrome with IPSS score > 0. (Appendix A) Myeloproliferative disorders (with the exclusion of chronic myeloid leukemia) a) Primary Myelofibrosis with Lile score of 1 or 2 (Appendix B) b) Polycythemia Vera or Essential Thrombocythemia transformed to AML or Myelofibrosis and PV "spent phase" Multiple Myeloma with stage II or III disease Severe aplastic anemia Conditions that increase Treatment Related Mortality (need one or more to be eligible): Greater or equal to 35 years of age; Ejection Fraction of less than 50%; DLCO less than 50% or FEV1/FVC < 80% of predicted value; Diabetes Mellitus; Renal insufficiency (serum creatinine abnormal); Hepatic dysfunction-transaminases, or alkaline phosphatase, or bilirubin twice the upper limit of normal; Prior recent history of systemic fungal infection; Multiple prior treatment regimens (equal to or more than 3); Significant Grade III or IV neurologic, cardiac, pulmonary, renal or hepatic toxicity from previous treatment; Prior Autologous or Allogeneic Stem Cell transplantation; Available Healthy Donor without any contraindications for donation. 5/6 or 6/6 related or unrelated donor (molecular typing for DRB1); Patient and/or responsible person able to understand and sign consent Exclusion Criteria: Pregnant and lactating women, or women unwilling to use contraception. HIV positive patient Unstable angina and uncompensated congestive heart failure (Zubrod of 3 or greater) Severe chronic pulmonary disease requiring oxygen (Zubrod of 3 or greater) Child's class C cirrhosis Unstable cerebral vascular disease or recent hemorrhagic stroke (less than 6 months) Patients with known allergy to rat serum products
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Malcolm K Brenner, MD
Organizational Affiliation
Baylor College of Medicine
Official's Role
Study Chair
Facility Information:
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
The Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

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Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation of Patients With Hematological Diseases

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