Stem Cell Transplant for Hematologic Diseases (HIMSUM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Baylor College of Medicine
Sponsor:
Collaborators:
Texas Children's Hospital
The Methodist Hospital System
Information provided by (Responsible Party):
George Carrum, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00058825
First received: April 11, 2003
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

Patients are being asked to participate in this study because they have a cancer in their blood, Fanconi's Anemia, or have been unsuccessfully treated for bone marrow failure such as Aplastic Anemia or Paroxysmal Nocturnal Hemoglobinuria. Any of these conditions could benefit from an allogeneic stem cell transplant using a donor that is related to the patient.

Stem cells are created in the bone marrow. They grow into different types of blood cells that the patient needs, including red blood cells, white blood cells, and platelets. In a transplant, the patient's own stem cells are killed and then replaced by stem cells from the donor.

Usually, patients are given very strong doses of chemotherapy prior to receiving a stem cell transplant. However, because of the patient's condition, they have a high risk of experiencing life-threatening treatment-related side-effects. Recently, some doctors have begun to use chemotherapy that does not cause as many side-effects before patients receive a transplant.

This research study adds CAMPATH 1H to a low-dose chemotherapy regimen, followed by an allogeneic stem cell transplantation. We want to see whether adding CAMPATH 1H to the transplant medications helps in treating the disease. We also want to see whether there are fewer life-threatening side-effects from the treatment. CAMPATH 1H is a drug that is still being studied. CAMPATH 1H stays active in the body for a long time after patients receive it, which means it may work longer at preventing graft-versus-host-disease (GvHD) symptoms.


Condition Intervention Phase
Hematologic Malignancies
Biological: Campath 1H
Drug: Fludarabine
Procedure: Stem Cell Transplant
Radiation: Total Body Irradiation (TBI)
Drug: FK506 (Tacrolimus) or Cyclosporin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Allogeneic Stem Cell Transplantation for Patients With Hematologic Diseases Using Haploidentical Family Donors and Sub-Myeloablative Conditioning With Campath 1H

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Treatment-related mortality of haploidentical allogeneic stem cell transplantation with non-myeloablative therapy incorporating Campath 1H. [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    To assess the treatment-related mortality of CD34-selected haploidentical allogeneic stem cell transplantation with non-myeloablative therapy incorporating the lymphodepleting MAb Campath 1H, in patients with hematologic diseases not eligible for conventional (myeloablative) therapy.


Secondary Outcome Measures:
  • Time to engraftment and incidence of graft failure. [ Time Frame: 100 days ] [ Designated as safety issue: No ]
    To assess the time to engraftment and incidence of graft failure in patients receiving this transplant regimen.

  • Safety, pharmacokinetics, and immunologic activity of Campath 1H. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess the safety, pharmacokinetics, and immunologic activity of Campath 1H when used as part of a sub-ablative conditioning regimen.

  • Clinical comparison of CLINIMACSs CD34 Reagent System and Isolex System. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate whether the CLINICMACs CD34 Reagent System can provide similar clinical results as the Isolex System.


Estimated Enrollment: 45
Study Start Date: August 2000
Estimated Study Completion Date: August 2024
Estimated Primary Completion Date: August 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stem Cell Transplant
Total body irradiation (TBI); Fludarabine and Campath 1H; FK506 or Cyclosporin; Stem Cell Transplant; G-CSF.
Biological: Campath 1H
Day -5 to Day -2: Campath 1H dose schedule as per institutional SOP.
Drug: Fludarabine
Day -5 to Day -2: Fludarabine 30 mg/m2.
Procedure: Stem Cell Transplant
Day 0: Donor stem cells infused.
Radiation: Total Body Irradiation (TBI)
Day -6: Total body irradiation of 600 cGy as two doses without blocks at a rate of less than or equal to 10 cGy/minute.
Drug: FK506 (Tacrolimus) or Cyclosporin
Day -2: FK506 or Cyclosporin as medically indicated to prevent GvHD.

Detailed Description:

Before treatment begins, stem cells will be collected from the donor's blood or bone marrow. The stem cells will be collected and frozen before we start to give the patient chemotherapy.

After admission to the hospital, patients will receive total body irradiation (very strong x-rays that kill cells in the bone marrow), Fludarabine and Campath 1H prior to the stem cell transplant (infusion of the donor's stem cells).

Starting 7 days after the transplant, the patient will be given G-CSF by subcutaneous injection, until a blood test shows that numbers of granulocytes (a type of white blood cell) in the blood are more than 1,000/uL. This is to help increase blood cell counts.

After transplantation, the patient will undergo several evaluations at different times. These are standard evaluations and tests performed for any patient who has received a stem cell transplant, as part of routine clinical monitoring.

We will also be looking at the patient's immune function (how the body protects itself to prevent and fight infections and diseases). To do this, blood tests will be performed at regular intervals (every 3 to 6 months) for 2 years.

Depending on how well the donor stem cells work in the body after the transplant, the patient may receive one or more Donor Leukocyte Infusions (DLI). This is when leukocytes (a type of white blood cell) collected from the same donor that provided the stem cells are given to the patient through a central line into a vein.

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  1. Diagnosis of myelodysplastic disorders; Fanconi's Anemia; Acute Myelogenous Leukemia (including secondary); Acute Lymphoblastic Leukemia; Multiple Myeloma; Plasma Cell Dyscrasia; lymphoproliferative disorders (Non-Hodgkin Lymphoma, Hairy Cell Leukemia, Chronic Lymphocytic Leukemia, and Hodgkin's Disease). Diagnosis of myelodysplastic disorders which is not good risk by IPSS: Fanconi's Anemia; Acute Myelogenous Leukemia (1st or subsequent relapse, or 2nd or subsequent CR, or refractory disease); Acute Lymphoblastic Leukemia in 2nd or subsequent remission or relapse or refractory disease; Philadelphia Chromosome-positive Chronic Myelogenous Leukemia (failed STI and interferon); Multiple Myeloma (Stage II or III); Lymphoma; Chronic Lymphocytic Leukemia (primary refractory or recurrent disease); Hodgkin's Disease (after relapse); Hemophagocytic Lymphohistiocytosis (failed chemotherapy and/or anti-viral therapy); bone marrow failure such as Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria; PNH (failed prior therapies).
  2. Conditions that increase treatment related mortality: (need one or more to be eligible): Age > / = 50 years; EF of less than 45%; DLCO less than 50% or FEVI 50-75% of predicted value; Diabetes Mellitus; Renal Insufficiency (but creatinine clearance not less than 25 mL/min); Prior recent history of systemic fungal infection; 3rd or greater remission of AML or ALL; Significant Grade III or IV neurologic or hepatic toxicity from previous treatment; More than 1 year from diagnosis (CML or Myeloma patients ONLY); Multiple types of treatment regimens (equal to or more than 3); Significant Grade III or IV neurologic or hepatic toxicity from previous treatment; Prior autologous or allogeneic stem cell transplantation.
  3. Haploidentical family member donor. This protocol is open to patients who lack a 5/6 or 6/6 HLA antigen-matched donor. Due to the increased risk of GvHD, patients with Fanconi Anemia and a 5/6 HLA match will also be eligible.

    For this protocol, the "best" donor will be defined as a first-degree haploidentical family member who matches at the greatest number of MHC loci. Matching will be determined by Class I and Class II DNA typing. The donor should be sufficiently healthy as to not be at increased risk from the stem cell mobilization procedure. Should more than one "equally" MHC-incompatible donor be identified, other selection criteria will include: age and size of donor, CMV status, and sex. The Principal Investigator will make final decisions.

  4. Available healthy donor without any contraindications for donation.
  5. Patient and/or legal representative and/or legal guardian able to understand and sign consent.
  6. Age between birth and 70 years.
  7. Women of child-bearing potential must have a negative pregnancy test.

EXCLUSION CRITERIA:

  1. Pregnant, lactating or unwilling to use contraception.
  2. HIV-positive patient.
  3. Uncontrolled intercurrent infection.
  4. Untreated blast crisis for CML.
  5. Uncontrolled high-grade lymphoproliferative disease / lymphoma.
  6. Unstable angina and uncompensated congestive heart failure (Zubrod of 3 or greater).
  7. Severe chronic pulmonary disease requiring oxygen (Zubrod of 3 or greater).
  8. Hemodialysis dependent.
  9. Active hepatitis or cirrhosis with total bilirubin, SGOT, and SGPT greater than 3X upper limit of normal.
  10. Unstable cerebral vascular disease and recent hemorrhagic stroke (less than 6 months).
  11. Active CNS disease from hematological disorder.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00058825

Contacts
Contact: George Carrum, MD 713-441-1450 gcarrum@bcm.edu
Contact: Romelia May rmay@tmhs.org

Locations
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: George Carrum, MD    713-441-1450    gcarrum@bcm.edu   
Contact: Romelia May       rmay@tmhs.org   
The Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: George Carrum, MD    713-441-1450    gcarrum@bcm.edu   
Contact: Romelia May       rmay@tmhs.org   
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital System
Investigators
Principal Investigator: George Carrum, MD Baylor College of Medicine; The Methodist Hospital
  More Information

No publications provided

Responsible Party: George Carrum, Principal Investigator, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00058825     History of Changes
Other Study ID Numbers: 8713-HIMSUM
Study First Received: April 11, 2003
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
Campath
stem cell transplant

Additional relevant MeSH terms:
Hematologic Diseases
Alemtuzumab
Cyclosporine
Cyclosporins
Fludarabine
Fludarabine phosphate
Anti-Infective Agents
Antifungal Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014