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

This study has been completed.
Sponsor:
Collaborators:
Texas Children's Hospital
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Information provided by (Responsible Party):
George Carrum, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00056966
First received: March 26, 2003
Last updated: June 27, 2012
Last verified: June 2012

March 26, 2003
June 27, 2012
November 2002
May 2005   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
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Complete list of historical versions of study NCT00056966 on ClinicalTrials.gov Archive Site
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 ] [ Designated as safety issue: No ]
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Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation of Patients With Hematological Diseases
Phase I/II Study of CD45 Antibodies and Alemtuzumab Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation of Patients With Hematological Diseases

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Hematologic Malignancy
  • Drug: ANTI-CD45
    400ug/kg Day-5 through Day-2
  • Drug: CAMPATH-1H
    Day -8 through Day -6 Dosed per Institutional SOP
    Other Names:
    • anti-CD52
    • alemtuzumab
  • Drug: FK506
    Day -2 through Day 30 dose adjusted to maintain level between 5-15 ng/ml.
    Other Name: tacrolimus
  • Drug: Fludarabine
    Day-8 through Day-5 30 mg/m2
  • Radiation: Total Body Irradiation
    Day-1 single dose 450 cGy
  • Procedure: Stem cell infusion
    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.
  • Experimental: 1
    recipients of HLA matched sibling transplants
    Interventions:
    • Drug: ANTI-CD45
    • Drug: CAMPATH-1H
    • Drug: FK506
    • Drug: Fludarabine
    • Radiation: Total Body Irradiation
    • Procedure: Stem cell infusion
  • Experimental: 2
    recipients of unrelated or mismatched family donor transplants
    Interventions:
    • Drug: ANTI-CD45
    • Drug: CAMPATH-1H
    • Drug: FK506
    • Drug: Fludarabine
    • Radiation: Total Body Irradiation
    • Procedure: Stem cell infusion
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
December 2006
May 2005   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. 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

  2. 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;

  3. Available Healthy Donor without any contraindications for donation. 5/6 or 6/6 related or unrelated donor (molecular typing for DRB1);
  4. 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

Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00056966
12472, ACHE
Yes
George Carrum, Baylor College of Medicine
Baylor College of Medicine
  • Texas Children's Hospital
  • The Methodist Hospital System
  • Center for Cell and Gene Therapy, Baylor College of Medicine
Study Chair: Malcolm K Brenner, MD Baylor College of Medicine
Baylor College of Medicine
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP