Allo Non-myeloablative SCT Utilizing Matched Family Member Stem Cells Purged Using Campath

This study has been completed.
Sponsor:
Collaborator:
Miltenyi Biotec GmbH
Information provided by (Responsible Party):
David Rizzieri, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00578942
First received: December 19, 2007
Last updated: August 27, 2013
Last verified: August 2013

December 19, 2007
August 27, 2013
May 2005
April 2013   (final data collection date for primary outcome measure)
Estimate toxicity and overall survival rates in three cohorts of patients treated with a non-myeloablative preparative regimen followed by matched related allogeneic stem cells for allogeneic transplantation. [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00578942 on ClinicalTrials.gov Archive Site
  • Evaluate immune recovery following non-myeloablative therapy in the three cohorts of patients. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Estimate response to transplant in the three cohorts of patients among those who enter with measurable disease. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Allo Non-myeloablative SCT Utilizing Matched Family Member Stem Cells Purged Using Campath
Allogeneic Non-myeloablative Stem Cell Transplantation Utilizing Matched Family Member Stem Cells Purged Using Campath-1H

Allogeneic bone marrow transplantation may cure or ameliorate illnesses of many types; however the toxicity of the procedure limits its broad applicability. Hematologic malignancies of all types have shown responses. The limiting effect of the historical methods of aggressive induction for allogeneic therapy were extremely toxic, requiring limiting those offered allogeneic therapy to the healthiest of the ill patients. Work over the last decade has shown that less toxic agents targeting the immune system effectively allowed engraftment with less effects on the patient's liver, lungs, and other vital organs. We and others have completed multiple trials showing the effective use of these less toxic, non-myeloablative, regimens for allogeneic therapy. Trials with fludarabine and cyclophosphamide at standard doses allow for 80% of patients to engraft donor cells. Some groups have added low doses of radiation to this combination, with 80-100% allogeneic engraftment. The lessened toxicity of this approach has been confirmed in multiple studies. Our group has combined the above combination of fludarabine and cyclophosphamide with the antibody CAMPATH 1H. This antibody is given to the patient to purge the immune system and prevent rejection. It also purges the T cells in the donated stem cells to minimize graft versus host disease (GVHD). This approach has been proven successful in multiple trials using standard more toxic ablative procedures. We have presented our preliminary results, with data on long term follow up for outcomes being collected. We have shown that 100% of patients with a malignancy or marrow failure treated with this regimen in our early phase trial engrafted donor cells. There was only an 8% severe GVHD risk, though the risk for infection remains high with a risk of fungal and viral infection about 5% each. Despite working with older, more infirmed patients, only 3/40 patients died within the first 100 days from therapy. Similar approaches on matched unrelated donors have been reported by other groups as well.

Allogeneic bone marrow transplantation may cure or ameliorate illnesses of many types; however the toxicity of the procedure limits its broad applicability. Hematologic malignancies of all types have shown responses. Those with marrow failure, such as aplasia, and hemoglobinopathies have further shown responses in multiple trials as well. Even patients with certain solid tumors, such as breast, renal cell, and melanoma have shown partial or complete responses to allogeneic therapy. The limiting effect of the historical methods of aggressive induction for allogeneic therapy were extremely toxic, requiring limiting those offered allogeneic therapy to the healthiest of the ill patients. Work over the last decade has shown that less toxic agents targeting the immune system effectively allowed engraftment with less effects on the patient's liver, lungs, and other vital organs. We and others have completed multiple trials showing the effective use of these less toxic, non-myeloablative, regimens for allogeneic therapy. Trials with fludarabine and cyclophosphamide at standard doses (patients are not ablated and recover blood counts in 2 weeks) allow for 80% of patients to engraft donor cells. Some groups have added low doses of radiation to this combination, with 80-100% allogeneic engraftment. The lessened toxicity of this approach has been confirmed in multiple studies, including our own data with the specific schema in this treatment plan reviewed below. Phase I results with this combination: Our group has combined the above combination of fludarabine and cyclophosphamide with the antibody CAMPATH 1H. This antibody is given to the patient to purge the immune system and prevent rejection. It also purges the T cells in the donated stem cells to minimize graft versus host disease (GVHD). This approach has been proven successful in multiple trials using standard more toxic ablative procedures. Our approach over the last 3 years has been very successful using this antibody with the less toxic non-myeloablative procedure and our trials have completed. We have presented our preliminary results, with data on long term follow up for outcomes being collected. We have shown that 100% of patients with a malignancy or marrow failure treated with this regimen in our early phase trial engrafted donor cells. There was only an 8% severe GVHD risk, though the risk for infection remains high with a risk of fungal and viral infection about 5% each. Despite working with older, more infirmed patients, only 3/40 patients died within the first 100 days from therapy. Similar approaches on matched unrelated donors have been reported by other groups as well. As the phase I feasibility trial is complete and the outcomes encouraging, this protocol will follow the same general treatment plan and allow further information to be gained for long term follow up of patients treated with this approach.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Lymphoma
  • Myeloma
  • Leukemia
  • Myelodysplasia
  • Solid Tumors
Drug: Campath Purged Non-myeloablative ASCT

Donor: Will receive G-CSF 8 mcg/kg/d subcutaneously bid (dose will be rounded to the nearest whole vial size). GM-CSF 15 mcg/kg/d sc or similar growth factor for donor mobilization. Donors will receive at least 3-6 doses of daily growth factor until adequate cells are mobilized.

Preparative regimen: Begins on day -5 and consist of 4 days of daily fludarabine at 30 mg/m2/d infused over 30 minutes, cyclophosphamide 500 mg/m2/d infused over 1 hour, 5 days of Campath-1H at 20 mg/d in 250 ml of D5 normal saline or normal saline infused over 3 hours.

Patient Evaluation: Wil occur 2-3 times per week by physical exam for toxicity through day 45.

Experimental: I
Lymphoma, myeloma, or marrow failure; leukemia or myelodysplasis; and solid tumors
Intervention: Drug: Campath Purged Non-myeloablative ASCT
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
49
April 2013
April 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must have their pathology reviewed and the diagnosis confirmed.
  • Performance status must be CALGB PS 0, 1, or 2
  • Patients must have a 6/6 HLA-matched related donor who is evaluated and deemed able to provide PBPCs and/or marrow by the transplant team.
  • HIV antibody negative.
  • Patients must test negative serum beta-HCG and must agree to use some form of adequate birth control during the periods they receive chemotherapy and any post-chemotherapy medications related to the transplant.
  • Patients must be 17 years of age or greater.
  • Patients must also have a resting MUGA and/or ECHO and PFTs with DLCO performed before transplant and found to be acceptable according to the treating institution's guidelines. The required minimum standards include MUGA and/or ECHO showing an EF of 40% and PFTs showing DLCO of 40%. Those with an EF 40-50%, undergo cardiac evaluation and consultation. Also, those with DLCO 40-50%, undergo pulmonary evaluation and consultation.
  • Specific populations for each disease category:

A) Hematologic malignancies Those with high risk or relapsed hematologic malignancy (including myeloid and lymphoid leukemias and lymphomas, myeloma or myelomatous like diseases, myeloproliferative disease, myelodysplasia). Those with good risk disease (first remission AML with inv 16 M4 Eos, M3 AML with t(15;17); or t(8;21) in first remission are not eligible).

B) Bone marrow failure

  1. Those specifically with idiopathic or secondary moderate, severe or very severe aplastic anemia (idiopathic or secondary) according to the accepted 'Camitta criteria' would be candidates.
  2. Those with diseases known to lead to severe marrow failure are eligible as well. These include those with myelofibrosis or PNH.

C) Solid Tumors Patients must have had a biopsy confirming disease recurrence (metastases) at some point in their history, unless the patient presented with metastatic disease, in which case the initial primary site biopsy is adequate.

  1. Patients with renal cell cancer, or melanoma will be eligible for this approach at this time. Patients will have had documented metastatic disease at some time in the past. Patients who are in remission or with residual disease after prior therapy for their metastatic disease are eligible, as there is no accepted cure for these patients with metastatic disease.
  2. Breast Cancer- Patients will have had documented metastatic disease at some time in the past. Patients who are in remission or with residual disease after prior therapy for their metastatic disease are eligible. Patient must have failed at least one chemotherapy regimen for their metastatic disease and 1 hormonal agent if they are receptor positive.

Exclusion Criteria:

  1. pregnant or lactating women,
  2. patients with other major medical or psychiatric illnesses which the treating physician feels could seriously compromise tolerance to this protocol, and
  3. Leukemia patients in first remission with good risk cytogenetics for leukemia [t(15;17); t(8,22)]
Both
17 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00578942
Pro00008380
Yes
David Rizzieri, Duke University Medical Center
David Rizzieri
Miltenyi Biotec GmbH
Principal Investigator: David Rizzieri, MD Duke University Health System
Duke University
August 2013

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