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Allogeneic Transplantation From Related Haploidentical Donors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Robert Lowsky, Stanford University
ClinicalTrials.gov Identifier:
NCT00185692
First received: September 12, 2005
Last updated: December 1, 2016
Last verified: January 2015
  Purpose
The purpose of the study is to evaluate the feasibility and safety of transplanting CD34+ selected hematopoietic cells from a haploidentical related donor following a nonmyeloablative regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG).

Condition Intervention Phase
Blood Cancer
Leukemia
Graft Versus Host Disease
Malignancy
CLL
NHL
Hodgkin's Disease
MDS
Procedure: non-myeloablative hematopoietic cell transplantation
Drug: Anti-Thymocyte Globulin
Drug: Cyclosporine
Drug: Mycophenolate Mofetil
Drug: G-CSF
Drug: Solumedrol
Drug: Acetaminophen
Drug: Diphenydramine
Drug: Hydrocortisone
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Cell Transplantation of Positively Selected CD34+ Cells and Defined Inoculum of T Cells From Related Haploidentical Donors for Older Patients With Indolent Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Engraftment of Haploidentical CD34+ Selected Blood Stem Cells in Older Patients or Those With Medical Co-morbidities Following Total Lymphoid Irradiation and Antithymocyte Globulin Transplant Conditioning [ Time Frame: 100 days ]
    number achieving donor cell engraftment (>95%) by day 90 after transplant.


Secondary Outcome Measures:
  • Acute Graft-versus-Host Disease (GVHD) Grade 2-4 Risk From Time of Transplant Until Day 90 Post-transplant [ Time Frame: 90 days ]
    GVHD grading system goes from 0-4 where grade 4 is the most severe. Grade 0 and 1 do not require systemic treatment, Grade 2-4 require treatment. This trial evaluated the risk of developing acute GVHD grades 2-4 within 90 days of transplant.


Enrollment: 16
Study Start Date: August 2000
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Transplantation of CD34+ cells

Week #1: Total Lymphoid Inrradiation (TLI) 120 cGy + Anti-thymocyte Globulin (ATG) 1.5 mg/kg + Solumedrol 1.0 mg/kg Daily for 5 days.

Week #2: TLI 120 cGy (3 days a week, double on the 4th day) 5 days of CSP (oraly) one day after TLI was started. 3 days of MMF 4 days after TLI was started.

Procedure: non-myeloablative hematopoietic cell transplantation
TLI and ATG infusion of the donor graft Post-transplant immunosuppression with cyclosporine and mycophenolate mofetil.
Other Name: Peripheral-blood stem-cell transplantation
Drug: Anti-Thymocyte Globulin
1.5 mg/kg QD x 5, IV. Dosage will be based on body weight. Purified, sterile IgG fraction of immune serum of rabbits immumixied with human thymus lymphocyte. This drug acts to modify the number and function of lymphocytes.
Other Name: ATG
Drug: Cyclosporine
6.25 mg/kg BID, PO.Mechanism of action is inhibition of T-cell activation by binding to a cytoplasmic protein (cyclophillin).
Other Names:
  • INN/BAN
  • USAN
  • CSA
Drug: Mycophenolate Mofetil
15 mg/kg Q 8 hours, PO. Inhibtis the enzme inosine monophsophate dehydrogenase (MPDII) noncompetitively which blocks the de nobo synthesis of guanosine required for DNA synthesis and has an effect on T and B cells.
Other Names:
  • MMF
  • CellCept
Drug: G-CSF
16 mg/kg, SQ Growth factor used to make bone marrow produce more blood cells
Other Names:
  • Granulocyte colony-stimulating factor
  • CSF 3
Drug: Solumedrol
1.0 mg/kg IV 2 hours prior to ATG Used to treat severe inflamation
Other Names:
  • 6-Methylprednisolone
  • Methylprednisolone Acetate
  • Methylprednisolone Sodium Succinate
Drug: Acetaminophen
650 mg PO, 30 minutes prior to infusion Pain reliever
Other Name: Tylenol
Drug: Diphenydramine
50 mg IV, 30 minutes prior to infusion Used to relieve allergy symptoms
Other Names:
  • Benadryl
  • Allermax
  • Q-Dryl
  • Diphen Cough
Drug: Hydrocortisone
100 mg IV, 1 hour prior to infusion Used to relieve itching, redness and swelling of the skin
Other Name: Hydrocortisone Sodium Phosphate

Detailed Description:
An alternative to conventional allogeneic bone marrow transplantation is by using a non-myeloablative conditioning regimen. This regime would consist of both; total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG). Used in combination to achieve engraftment of haploidentical CD34+ selected peripheral blood stem cells in older patients or patients with underlying medical conditions that preclude standard allogeneic treatment. The expected results of this transplant regime will be expected to result in hematopoietic and immunologic reconstitution, decreased deaths related to the treatment regimen and decreased gravft-vs-host disease (GVHD).
  Eligibility

Ages Eligible for Study:   12 Months and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 50 years with hematologic malignancies treatable by a mixed chimera allogeneic HCT.
  • For patients ≤ 50 years of age with hematologic malignacies treatable with mixed chimera HCT who because of pre-exisiting medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional transplants.
  • Indolent advanced stage NHL, CLL, HD - Must have received and failed front-line therapy.
  • Multiple myeloma (Stage II or III) - Must have received prior chemotherapy. Consolidation after prior autografting is permitted.
  • AML/ALL - Must be in complete hematologic remission and have received cytotoxic chemotherapy at some stage before transplant. Patients with molecular or cytogenetic relapse will be accepted providing a donor is available. Patients with persistent or refractory disease will be considered on a case by case basis and transplants must be approved by the principal investigator.
  • CML - Patients will be accepted in chronic or accelerated phase. Patients who have received prior autografts after high dose therapy or have undergone intensive chemotherapy for either peripheral blood stem cell mobilization or treatment of advanced CML may be enrolled provided they are in CR, chronic phase or accelerated phase.
  • MDS - All patients with MDS will be eligible for this protocol, however, those patients with >10% blasts will require chemotherapy to reduce the blast % to < 10%.
  • SAA - Patients with severe aplastic anemia who have failed front line therapy.
  • A fully HLA-identical sibling donor is not available.
  • A matched unrelated donor has not been identified.
  • A haploidentical related donor is available who is in good health and does not have contraindications to donation.

Exclusion Criteria:

  • Patients with rapidly progressive intermediate or high grade NHL
  • Uncontrolled CNS involvement with disease
  • Fertile men
  • Women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Females who are pregnant
  • Cardiac function: ejection fraction < 30% or cardiac failure requiring therapy
  • Pulmonary: DLCO < 40% predicted and/or receiving supplementary continuous oxygen
  • Liver function abnormalities: elevation of bilirubin to > 4 mg/dl and/or transaminases > 3x the upper limit of normal. If hyperbilirubinemai is due to a known cause that will not increase the risks of transplant, than this upper limit may be exceeded.
  • Renal: creatinine clearance < 50 cc/min (24 hour urine collection)
  • Karnofsky performance score < 60%
  • Patients with poorly controlled hypertension.
  • Documented fungal disease that persists despite treatment
  • HIV positive patients.
  • Hepatitis B and C positive patients will be evaluated on a case by case basis
  • Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or principal investigator would place the patient at unacceptable risk from this regimen.
  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: NCT00185692

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Robert Lowsky Stanford University
  More Information

Responsible Party: Robert Lowsky, Associate Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00185692     History of Changes
Other Study ID Numbers: IRB-13371
75117 ( Other Identifier: Stanford University Alternate IRB Approval Number )
BMT 124 ( Other Identifier: OnCore )
Study First Received: September 12, 2005
Results First Received: December 1, 2016
Last Updated: December 1, 2016
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Neoplasms
Graft vs Host Disease
Hodgkin Disease
Hematologic Neoplasms
Immune System Diseases
Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Neoplasms by Site
Hematologic Diseases
Cyclosporins
Cyclosporine
Mycophenolic Acid
Mycophenolate mofetil
Antilymphocyte Serum
Lenograstim
Acetaminophen
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Methylprednisolone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone acetate
Methylprednisolone
Hydrocortisone
Prednisolone hemisuccinate
Prednisolone phosphate

ClinicalTrials.gov processed this record on April 26, 2017