A Study to Lower the Occurrences and Severity of Graft-versus-host Disease - Full Text View

Sponsor:	Baylor College of Medicine
Information provided by:	Baylor College of Medicine
ClinicalTrials.gov Identifier:	NCT00368355

Purpose

In an effort to lower the occurrence and severity of graft-versus-host disease in patients and to lower the rate of transplant failure, the investigators would like to specially treat the donor's blood cells to remove cells that are most likely to attack your tissues. This will occur in combination with an intense conditioning treatment that you will receive before your transplant.

Condition	Intervention	Phase
Graft vs Host Disease	Drug: Ara-C Drug: Cyclophosphamide Drug: MESNA Drug: Campath-1H Procedure: Total Body Irradiation Procedure: Stem cell infusion	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	CD-34 Selection for Ex-vivo T-Cell Depletion of Mobilized Peripheral Blood Stem Cells for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts Receiving Intensive Conditioning

Resource links provided by NLM:

Genetics Home Reference related topics: familial hemophagocytic lymphohistiocytosis X-linked lymphoproliferative disease

Drug Information available for: Cyclophosphamide Cytarabine hydrochloride Mesna Campath Alemtuzumab

U.S. FDA Resources

Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:

Occurrence of GVHD [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
Rate of stable engraftment [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
To estimate the length of remission in patients with relapsed or high risk leukemia in second or greater CR treated with myeloablative chemotherapy, radiotherapy and CD34 selected peripheral blood stem cells from haploidentical related donors. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment:	18
Study Start Date:	April 2000
Estimated Study Completion Date:	April 2015
Estimated Primary Completion Date:	April 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: Ara-C day-8 through day-5 3 g/m2 q 12 hours Drug: Cyclophosphamide day-7 and day-6 45 mg/kg (at 2000) Drug: MESNA day-7 and day-6 9 mg/kg Drug: Campath-1H day-3 through day-1 per institutional SOP Procedure: Total Body Irradiation day-4 through day-1 175 cGy x 2 at 24 cGy/min Procedure: Stem cell infusion At the time of stem cell rescue (day 0), CD34+ cells will be infused through a central venous catheter as outlined in CAGT SOPs

Arms

Assigned Interventions

Experimental: 1

Drug: Ara-C

day-8 through day-5

3 g/m2 q 12 hours

Drug: Cyclophosphamide

day-7 and day-6

45 mg/kg (at 2000)

Drug: MESNA

day-7 and day-6

9 mg/kg

Drug: Campath-1H

day-3 through day-1

per institutional SOP

Procedure: Total Body Irradiation

day-4 through day-1

175 cGy x 2 at 24 cGy/min

Procedure: Stem cell infusion

At the time of stem cell rescue (day 0), CD34+ cells will be infused through a central venous catheter as outlined in CAGT SOPs

Detailed Description:

Patients will receive cytosine arabinoside (3 g/m2) IV every 12 hours for 6 doses starting at 1400 hours on Day-8. Cyclophosphamide (45 mg/kg) will be given on Day-7 and Day-6. MESNA (45 mg/kg; divided into 5 doses) will be administered 15 minutes prior to each dose of Cyclophosphamide and 3, 6, 9, and 12 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 10 cGy/min.

Protocol Day/Treatment/Dose

8 Ara-C 3 g/m2 q 12 hours (start at 1400)
7 Ara-C 3 g/m2 q 12 hours Cyclophosphamide 45 mg/kg (at 2000) MESNA 9 mg/kg
6 Ara-C 3 g/m2 q 12 hours Cyclophosphamide 45 mg/kg (at 2000) MESNA 9 mg/kg
5 Ara-C g/m2 q 12 hours (last 0200)
4 TBI 175 cGy x 2 at 24 cGy/min
3 TBI 175 cGy x 2 at 24 cGy/min Campath 1H IV over 4 hours
2 TBI 175 cGy x 2 at 24 cGy/min Campath 1H IV over 4 hours
1 TBI 175 cGy x 2 at 24 cGy/min Campath 1H IV over 4 hours
0 Stem cell reinfusion

Campath 1H Dosing

Children
- 5 - 15 kg: 3 mg IV in 30 ml NS
- 15.1 - 30 kg: 5 mg IV in 50 ml NS
- > 30 kg: 10 mg IV in 100 ml NS
Adolescents and adults: 10 mg IV in 100 ml NS

Eligibility

Ages Eligible for Study:	up to 25 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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
Age less than or equal to 25 years of age
Patients with ALL or high grade (stage III or IV) NHL after first relapse or with 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)
Donor cells should be collected and frozen before conditioning starts

Exclusion Criteria:

Patients with a life expectancy (< / = 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 40 cc/1.73 m2)
Patients with pre-existing severe restrictive pulmonary disease (FVC less than 40% of predicted)
Patients with severe hepatic disease (direct bilirubin greater than 3 ug/dl or SGPT greater than 500 ug/dl)
Patients with severe personality disorder or mental illness
Patients with a severe infection that on evaluation by the principal investigator precludes ablative chemotherapy or successful transplantation
Patients with documented HIV positivity

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00368355

Contacts

Contact: Robert K. Krance, MD

832-824-4661

rkrance@bcm.tmc.edu

Locations

United States, Texas
Baylor College of Medicine	Recruiting
Houston, Texas, United States, 77030
Contact: Robert A. Krance, MD 832-824-4661 rakrance@txccc.org
Sub-Investigator: George Carrum, MD
Sub-Investigator: Malcolm K Brenner, MD, PhD
Sub-Investigator: Helen E Heslop, MD
Sub-Investigator: Adrian P Gee, MD
Sub-Investigator: Stephen M Gottschalk, MD
Sub-Investigator: Catherine M Bollard, MD
Sub-Investigator: Hao Liu, PhD
Principal Investigator: Robert A Krance, MD

Sponsors and Collaborators

Baylor College of Medicine

Investigators

Principal Investigator:	Robert K. Krance, MD	Baylor College of Medicine
Principal Investigator:	Helen H. Heslop, MD	Baylor Collge of Medicine

More Information

No publications provided

Responsible Party:	Robert Krance, MD, Baylor College of Medicine
ClinicalTrials.gov Identifier:	NCT00368355 History of Changes
Other Study ID Numbers:	8701-MOHEL, MOHEL
Study First Received:	September 21, 2005
Last Updated:	August 12, 2011
Health Authority:	United States: Institutional Review Board; United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:

Lack of suitable conventional donor
Rapidly progressive disease no unrelated donor
ALL
High grade (stage III or IV) NHL after first relapse
Primary refractory disease
Myelodysplastic Syndrome

AML first relapse or w/primary ref dis
CML
Hemophagocytic lymphohistiocytosis (HLH)
Familial hemophagocytic lymphohistiocytosis (FLH)
Viral-associated hemophagocytic syndrome (VAHS)
X-linked lymphoproliferative disease (XLP)

Additional relevant MeSH terms:

Graft vs Host Disease
Lymphohistiocytosis, Hemophagocytic
Immune System Diseases
Histiocytosis, Non-Langerhans-Cell
Histiocytosis
Lymphatic Diseases
Cyclophosphamide
Campath 1G
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 February 09, 2012