MDACC Study Summary 2005-0513

Study Summary
No. 2005-0513:.......Blood And Marrow Transplantation; Hematologic Disorder......Paolo Anderlini......Stem Cell Transplantation and Cellular Therapy

Study Summary Title



Study Summary Number:	2005-0513

Study Title:	Fludarabine-based conditioning for allogeneic marrow transplantation from HLA-compatible unrelated donors in severe aplastic anemia

Physician

New Patient Referral



Name:	Paolo Anderlini	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Stem Cell Transplantation and Cellular Therapy	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-8750 Contact us about clinical trials

General Information



Disease Group:	Blood And Marrow Transplantation Hematologic Disorder	Supported By:	N/A

Phase of Study:	Phase I/Phase II	Return Visit:	2-4 times a week until day 100 after transplant, then every 2-4 months thereafter as per current BMT guidelines

Treatment Agents:	Antithymocyte Globulin Cyclophosphamide Fludarabine	Home Care:	Antibiotics, antifungals, antivirals, intravenous fluids (supportive care)

Treatment Loc:	Independent Multicenter Arrangements

Estimated Length of Stay in Houston:	4-5 weeks (uncomplicated cases)


Description/ Intervention:	The goal of this clinical research study is to find out the best dose of cyclophosphamide that can be given with fludarabine, antithymocyte globulin (ATG), and low-dose total body irradiation (TBI) to patients before a bone marrow transplant to decrease the risks related to the transplant while not decreasing the effectiveness of the transplant from an unrelated donor.

Study Objectives / Outcomes

Primary
General: Feasibility and toxicity of employing fludarabine-based conditioning to reduce cyclophosphamide doses and transplant-related toxicity while maintaining (or ideally improving) engraftment and survival in allogeneic donor marrow transplantation from matched (and mismatched) unrelated donors (MUD) in patients with severe aplastic anemia (SAA). The primary endpoint of the study is selection of the optimal CY dose based on Day 100 assessments of graft failure (primary and secondary), major regimen-related toxicity and early deaths.

Primary endpoints of the dose-finding (Phase I) portion of the study: engraftment as well as major regimen-related toxicity and early deaths. The Phase I portion of the study will test cyclophosphamide dose de-escalation.

Primary endpoint of the Phase II portion of the study: two-year post-transplant survival achieved with the level of CY dose reduction selected in the dose-finding portion of the study.

Secondary
Secondary endpoints of clinical interest include secondary graft failure and acute and chronic GVHD.

Study Status Information



Study Activation / Registration Date:	02/07/2006

IRB Review and Approval Date:	09/07/2005

Study Type:	Therapeutic

Recruitment Status:	Open

Projected Accrual:	81

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Patients up to 65 years of age at time of registration with a diagnosis of severe aplastic anemia (SAA). SAA is defined as follows: � Bone marrow cellularity < 25%, or marrow cellularity < 50% but with < 30% residual hematopoietic cells. Two out of three of the following (in peripheral blood): neutrophils < 0.5 x 10^9/L; platelets < 20 x 10^9/L; reticulocytes < 20 x 10^9/L. SAA diagnostic criteria may be applied to assessment at initial diagnosis or to the follow-up assessments.

2) Patient must have an available unrelated donor with a 7/8 or 8/8 match for HLA-A, B, C and DRB1 antigen. Typing is by DNA techniques: intermediate resolution for A, B and C, and high resolution for DRB1. HLA-DQ typing is recommended but will not count in the match

3) Patient and/or legal guardian able to provide signed informed consent.

4) Matched unrelated donor must consent to provide marrow allograft.

5) Patients with adequate organ function as measured by: a) cardiac: left ventricular ejection fraction at rest must be > 40% or shortening fraction > 20% b) hepatic: serum total bilirubin < 2x upper limit of normal for age as per local laboratory; ALT and AST < 4x upper limit of normal for age as per local laboratory; c) renal: serum creatinine < 2x upper limit of normal for age (as per local laboratory). d) pulmonary FEV1, FVC and DLCO (corrected for Hb) > 50% predicted. For pts where pulse oxymetry is perfomed, O2 saturation > 92%

6) The diagnosis of Fanconi anemia must be excluded in patients younger than 18 years of age by diepoxybutane (DEB) testing on peripheral blood or comparable testing or marrow.

Exclusion Criteria:

1) Clonal cytogenetic abnormalities associated with MDS or AML on marrow examination.

2) Diagnosis of other "congenital" aplastic anemias such as: Diamond-Blackfan; Shwachmann-Diamond; congenital amegakaryocytosis.

3) Symptomatic or uncontrolled cardiac failure or coronary artery disease.

4) Karnofsky performance status < 60% or Lansky < 40% for patients < 16 years of old.

5) Uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms). Patients with fevers despite broad-spectrum antimicrobials but no clinical or hemodynamic evidence of sepsis will be allowed.

6) Seropositive for the human immunodeficiency virus (HIV).

7) Pregnancy (positive �-HCG) or breastfeeding.

8) Presence of large accumulation of ascites or pleural effusions, which would be a contraindication to the administration of methotrexate for GVHD prophylaxis.

9) Known severe or life-threatening allergy or intolerance to ATG or cyclosporine/tacrolimus.

10) Planned administration of alemtuzumab (Campath-1H) or other investigational agents as alternative agent for GVHD prophylaxis.

11) Concomitant enrollment in a Phase I study.

12) Positive patient anti-donor lymphocyte crossmatch in HLA-A or B mismatched transplants (test recommended but not mandatory). The definition of match is in Section 2.2.1.

13) Prior allogeneic marrow or stem cell transplantation.

14) Patients with prior malignancies except resected basal cell carcinoma or treated carcinoma in-situ. Cancer treated with curative intent < 5 years previously will not be allowed unless approved by the Medical Monitor or Protocol Chair. Cancer treated with curative intent > 5 years previously will be allowed.

Links

Registration Number: NCT00474747
Study Information on Clinical Trials Registry (clinicaltrials.gov)