Allogeneic Transplantation From Related Haploidentical Donors

November 17, 2019 updated by: Robert Lowsky, Stanford University

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • 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:
  • CSA
  • USAN
  • INN/BAN
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:
  • CellCept
  • MMF
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:
  • Methylprednisolone Acetate
  • Methylprednisolone Sodium Succinate
  • 6-Methylprednisolone
Drug: Acetaminophen
650 mg PO, 30 minutes prior to infusion Pain reliever
Other Names:
  • 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 Names:
  • Hydrocortisone Sodium Phosphate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
100 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2000

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)

December 1, 2010

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (Estimate)

September 16, 2005

Study Record Updates

Last Update Posted (Actual)

December 4, 2019

Last Update Submitted That Met QC Criteria

November 17, 2019

Last Verified

January 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-13371
  • 75117 (Other Identifier: Stanford University Alternate IRB Approval Number)
  • BMT124 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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