LeukemiaPhase 1NCT00586547
Evaluating the Use of RFT5-dgA to Deplete Alloreactive Cells Prior to Haploidentical Stem Cell Transplantation
A Phase 1 study testing T-Cell Infusion Dose Level -1, T-Cell Infusion Dose Level 1 and T-Cell Infusion Dose Level 2 in people with Leukemia and Cancer, run by Baylor College of Medicine at 2 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- What is being tested?
- T-Cell Infusion Dose Level -1, T-Cell Infusion Dose Level 1 and T-Cell Infusion Dose Level 2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2000to Sep 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Methodist Hospital
Houston, Texas, 77030
Texas Children's Hospital
Houston, Texas, 77030
About this study
Official title: A Phase I Trial Evaluating The Use of RFT5-dgA to Deplete Alloreactive Cells PriorTo Haploidentical Stem Cell Transplantation
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.
Read the 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).
- Being tested
- T-Cell Infusion Dose Level -1, T-Cell Infusion Dose Level 1, T-Cell Infusion Dose Level 2, T-Cell Infusion Dose Level 3, T-Cell Infusion- Dose Level 4
- Keywords
- Haploidentical, Stem Cell Transplant, Graft-Versus-Host disease
- Medical subject headings
- Leukemia, Neoplasms, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
T-Cell Infusion Dose Level -1Biological
(1 x 10^3 T cells/Kg)
T-Cell Infusion Dose Level 1Biological
(1 x 10^4 T cells/Kg)
T-Cell Infusion Dose Level 2Biological
(1 x 10^5 T cells/Kg)
T-Cell Infusion Dose Level 3Biological
(1 x 10^6 T cells/Kg)
T-Cell Infusion- Dose Level 4Biological
(5 x 10^6 T cells/Kg)
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | After patients have completed preparation to receive cells, they will be treated at one of five dose levels. Receives: Biological: T-Cell Infusion Dose Level -1; Biological: T-Cell Infusion Dose Level 1; Biological: T-Cell Infusion Dose Level 2; Biological: T-Cell Infusion Dose Level 3; Biological: T-Cell Infusion- Dose Level 4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 100
Secondary outcomes (1)
To measure their overall and disease free survival.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2008 (estimated)
- Study startJul 2000
- Primary completionSep 2008
- Study completionSep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- University of Texas, Southwestern Medical Center at Dallas
- Responsible party
- Principal investigator, Malcolm Brenner, Baylor College of Medicine
- Investigators
- Malcolm Brenner, MB, PhD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00586547
- Sponsor's protocol ID
- H-9033
- Status last verified
- Jan 2020
- First submitted
- 21 Dec 2007
- Last updated
- 21 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial Evaluating The Use of RFT5-dgA to Deplete Alloreactive Cells PriorTo Haploidentical Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT00586547
- Acronym / sponsor ID
- H-9033
- Keywords
- Haploidentical, Stem Cell Transplant, Graft-Versus-Host disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- University of Texas, Southwestern Medical Center at Dallas
- Study start
- Jul 2000
- Primary completion
- Sep 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 4 Jan 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Biological: T-Cell Infusion Dose Level -1, Biological: T-Cell Infusion Dose Level 1, Biological: T-Cell Infusion Dose Level 2, Biological: T-Cell Infusion Dose Level 3, Biological: T-Cell Infusion- Dose Level 4After patients have completed preparation to receive cells, they will be treated at one of five dose levels. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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)
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| T-Cell Infusion Dose Level -1(1 x 10^3 T cells/Kg) | Biological | Treatment |
| T-Cell Infusion Dose Level 1(1 x 10^4 T cells/Kg) | Biological | Treatment |
| T-Cell Infusion Dose Level 2(1 x 10^5 T cells/Kg) | Biological | Treatment |
| T-Cell Infusion Dose Level 3(1 x 10^6 T cells/Kg) | Biological | Treatment |
| T-Cell Infusion- Dose Level 4(5 x 10^6 T cells/Kg) | Biological | Treatment |
Primary outcome
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
1 secondary outcome
To measure their overall and disease free survival.
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Malcolm Brenner, MB, PhD principal investigator
Baylor College of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing T-Cell Infusion Dose Level -1, T-Cell Infusion Dose Level 1 and T-Cell Infusion Dose Level 2 in people with Leukemia and Cancer, run by Baylor College of Medicine at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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. (time frame: 100). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2020.