Know Cancer

forgot password

A Phase I Trial Evaluating The Use of RFT5-dgA to Deplete Alloreactive Cells PriorTo Haploidentical Stem Cell Transplantation

Phase 1
Not Enrolling
Leukemia, Cancer

Thank you

Trial Information

A Phase I Trial Evaluating The Use of RFT5-dgA to Deplete Alloreactive Cells PriorTo Haploidentical Stem Cell Transplantation

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

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).

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

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:


Safety Issue:


Principal Investigator

Malcolm Brenner, MB, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Baylor College of Medicine


United States: Food and Drug Administration

Study ID:




Start Date:

July 2000

Completion Date:

September 2008

Related Keywords:

  • Leukemia
  • Cancer
  • Haploidentical
  • Stem Cell Transplant
  • Graft-Versus-Host disease
  • Leukemia



Methodist Hospital Houston, Texas  77030
Texas Children's Hospital Houston, Texas