Allogeneic Transplantation From Related Haploidentical Donors

NCT ID: NCT00185692

Last Updated: 2019-12-04

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-08-31

Study Completion Date

2010-12-31

Brief Summary

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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).

Detailed Description

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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).

Conditions

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Blood Cancer Leukemia Graft Versus Host Disease Malignancy CLL NHL Hodgkin's Disease MDS

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

non-myeloablative hematopoietic cell transplantation

Intervention Type PROCEDURE

TLI and ATG infusion of the donor graft Post-transplant immunosuppression with cyclosporine and mycophenolate mofetil.

Anti-Thymocyte Globulin

Intervention Type DRUG

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.

Cyclosporine

Intervention Type DRUG

6.25 mg/kg BID, PO.Mechanism of action is inhibition of T-cell activation by binding to a cytoplasmic protein (cyclophillin).

Mycophenolate Mofetil

Intervention Type DRUG

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.

G-CSF

Intervention Type DRUG

16 mg/kg, SQ Growth factor used to make bone marrow produce more blood cells

Solumedrol

Intervention Type DRUG

1.0 mg/kg IV 2 hours prior to ATG Used to treat severe inflamation

Acetaminophen

Intervention Type DRUG

650 mg PO, 30 minutes prior to infusion Pain reliever

Diphenydramine

Intervention Type DRUG

50 mg IV, 30 minutes prior to infusion Used to relieve allergy symptoms

Hydrocortisone

Intervention Type DRUG

100 mg IV, 1 hour prior to infusion Used to relieve itching, redness and swelling of the skin

Interventions

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non-myeloablative hematopoietic cell transplantation

TLI and ATG infusion of the donor graft Post-transplant immunosuppression with cyclosporine and mycophenolate mofetil.

Intervention Type PROCEDURE

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.

Intervention Type DRUG

Cyclosporine

6.25 mg/kg BID, PO.Mechanism of action is inhibition of T-cell activation by binding to a cytoplasmic protein (cyclophillin).

Intervention Type 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.

Intervention Type DRUG

G-CSF

16 mg/kg, SQ Growth factor used to make bone marrow produce more blood cells

Intervention Type DRUG

Solumedrol

1.0 mg/kg IV 2 hours prior to ATG Used to treat severe inflamation

Intervention Type DRUG

Acetaminophen

650 mg PO, 30 minutes prior to infusion Pain reliever

Intervention Type DRUG

Diphenydramine

50 mg IV, 30 minutes prior to infusion Used to relieve allergy symptoms

Intervention Type DRUG

Hydrocortisone

100 mg IV, 1 hour prior to infusion Used to relieve itching, redness and swelling of the skin

Intervention Type DRUG

Other Intervention Names

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Peripheral-blood stem-cell transplantation ATG INN/BAN USAN CSA MMF CellCept Granulocyte colony-stimulating factor CSF 3 6-Methylprednisolone Methylprednisolone Acetate Methylprednisolone Sodium Succinate Tylenol Benadryl Allermax Q-Dryl Diphen Cough Hydrocortisone Sodium Phosphate

Eligibility Criteria

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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.
Minimum Eligible Age

12 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Stanford University

OTHER

Sponsor Role lead

Responsible Party

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Robert Lowsky

Associate Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Robert Lowsky

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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Stanford University School of Medicine

Stanford, California, United States

Site Status

Countries

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United States

Other Identifiers

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75117

Identifier Type: OTHER

Identifier Source: secondary_id

BMT124

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-13371

Identifier Type: -

Identifier Source: org_study_id

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