Evaluating the Use of RFT5-dgA to Deplete Alloreactive Cells Prior to Haploidentical Stem Cell Transplantation

This study has been completed.
Sponsor:
Collaborator:
UTSW-Dallas
Information provided by:
Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00586547
First received: December 21, 2007
Last updated: December 2, 2009
Last verified: October 2009
  Purpose

This study is designed to determine the number of donor lymphocytes that can be given to recipients of haploidentical stem cell transplants after depletion of recipient-reactive T lymphocytes by ex-vivo treatment with a fixed dose of RFT5-dgA immunotoxin, and will result in a rate of Grade III/IV GVHD of < / = 25%, to analyze immune reconstitution in these patients, and to measure their overall and disease free survival, at 100 days and at 1 year.


Condition Intervention Phase
Leukemia
Cancer
Drug: Ara-C
Drug: Cyclophosphamide
Drug: Mesna
Biological: Campath 1H
Radiation: TBI
Procedure: Stem Cells Infusion
Procedure: T-cell Infusion
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial Evaluating The Use of RFT5-dgA to Deplete Alloreactive Cells PriorTo Haploidentical Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Determining the number of donor lymphocytes given to recipients of haploidentical stem cell transplants after depletion of recipient-reactive T lymphocytes by ex-vivo treatment with a fixed dose of RFT5-dgA immunotoxin. [ Time Frame: 100 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To measure their overall and disease free survival. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 24
Study Start Date: July 2000
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Ara-C

    Day -8,-7,-6, and-5:

    (3g/m2) IV every 12 hours for 6 doses

    Other Name: cytosine
    Drug: Cyclophosphamide

    Days -7 and -6:

    Intravenous 45mg/kg

    Other Name: Cytoxan
    Drug: Mesna
    (45mg/kg, divided into 5 doses) administered 15 minutes prior to each dose of cyclophosphamide and 3, 6, 9 and 12 hours after each dose of cyclophosphamide.
    Biological: Campath 1H

    Days -3,-2, and -1:

    Intravenous, according to age and weight.

    Radiation: TBI

    Days -4,-3,-2, and-1:

    Total dose 14.0 Gy will be delivered in 8 fractions of 1.75 Gy in two fractions. The dose rate will be 10cGy/min.

    Procedure: Stem Cells Infusion
    once
    Procedure: T-cell Infusion

    30 Days after stem cell infusion

    Patients will be entered starting at level 1, according to the following doses:

    Dose level -1 (1 x 10^3 T cells/Kg); Dose level 1 (1 x 10^4 T cells/Kg); Dose level 2 (1 x 10^5 T cells/Kg); Dose level 3 (1 x 10^6 T cells/Kg); Dose level 4 (5 x 10^6 T cells/Kg).

Detailed Description:

Patients will receive cytosine arabinoside (3g/m^2) IV every 12 hours for 6 doses starting at 1400 hours on day -8. Cyclophosphamide (45mg/kg) will be given on Day -7 and Day -6. MESNA (45mg/kg, divided into 5 doses) will be administered 15 minutes prior to each dose of cyclophosphamide and 3, 6, 9 and12 hours after each dose of cyclophosphamide. Campath 1H IV will be given on Days -3, -2 and -1. TBI, total dose 14.0 Gy will be delivered in 8 fractions of 1.75 Gy in two fractions per day beginning Day -4. The dose rate will be 10cGy/min.

Approximately thirty days following transplantation (day +30), the cryopreserved T cells will be thawed and infused through a catheter line with normal saline.

This study will begin with a dose of T cells known not to cause GvHD even in haploidentical recipients, even when the T cells administered have not first been allodepleted. A subset of patients who achieved engraftment will be included in the dose escalation study of allodepleted T-cells treated with RFT5-dgA. A continual reassessment method based on a logistic dose-response curve with cohorts of size 2 will be employed to determine the MTD. Cohorts of size 2 will be accrued beginning at dose level 1 and the dose-response curve is estimated after toxicity outcome is observed to determine the recommended dose level for the next patient cohort. Each and every patient will receive up to five additional injections of T cells at the same dose, at monthly intervals, provided there is no evidence of grade 2 or higher GVHD, until total T cell numbers are > 1000/ul

Patients will be entered starting at level 1, according to the following doses:

Dose level -1 (1 x 10^3 T cells/Kg); Dose level 1 (1 x 10^4 T cells/Kg); Dose level 2 (1 x 10^5 T cells/Kg); Dose level 3 (1 x 10^6 T cells/Kg); Dose level 4 (5 x 10^6 T cells/Kg).

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • ALL or high grade NHL that is Stage III or IV and has relapsed or is considered to be primary refractory disease.
  • Myelodysplastic syndrome.
  • AML after first relapse or with primary refractory disease.
  • CML hemophagocytic lymphohistiocytosis (HLH)
  • Familial hemophagocytic lymphohistiocytosis (FLH)
  • Viral-associated hemophagocytic syndrome (VAHS)
  • X-linked lymphoproliferative disease (XLP)
  • Patients with Severe chronic active Epstein Barr virus infection (SCAEBV) with predilection for T- or NK-cell malignancy
  • Lack of suitable conventional donor (i.e. 5/6 or 6/6 related or 5/6 or 6/6 unrelated donor) or presence of a rapidly progressive disease not permitting time to identify an unrelated donor.
  • Donor cells should be collected and frozen before conditioning starts.

Exclusion Criteria:

  • Patients with a life expectancy (< or = to 6 weeks) limited by diseases other than leukemia.
  • Patients with symptomatic cardiac disease, or evidence of significant cardiac disease by echocardiogram (i.e. shortening fraction < 25%)
  • Patients with severe renal disease (i.e. creatinine clearance less than 40cc/1.73m2)
  • Patients with pre-existing severe restrictive pulmonary disease (FVC less than 40% of predicted)
  • Patients with severe hepatic disease (direct bilirubin greater than 3ug/dl or SGPT greater than 500ug/dl)
  • Patients with severe personality disorder or mental illness that would preclude compliance with the study
  • Patients with a severe infection that on evaluation by the Principal Investigator precluded ablative chemotherapy or successful transplantation
  • Patients with documented HIV positivity
  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: NCT00586547

Locations
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Methodist Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
UTSW-Dallas
Investigators
Principal Investigator: Malcolm Brenner, MB, PhD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Malcolm Brenner, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00586547     History of Changes
Obsolete Identifiers: NCT00622297
Other Study ID Numbers: H-9033
Study First Received: December 21, 2007
Last Updated: December 2, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
Haploidentical
Stem Cell Transplant
Graft-Versus-Host disease

Additional relevant MeSH terms:
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Alemtuzumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on August 21, 2014