MDACC Study Summary 2008-0227

Study Summary
No. 2008-0227:.......Leukemia; Lymphoma; Myeloma......Marcos de Lima......Stem Cell Transplantation and Cellular Therapy

Study Summary Title



Study Summary Number:	2008-0227

Study Title:	Multi-institutional Trial of Allogeneic Bone Marrow Transplantation for Hematologic Malignancies using HLA-matched Related or Unrelated Donors with Fludarabine and IV Busulfan as Pre-transplant Conditioning followed by Post-transplant Immunosuppression with High-dose Cyclophosphamide.

Physician

New Patient Referral



Name:	Marcos de Lima	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:	Leukemia Lymphoma Myeloma	Supported By:	Otsuka Pharmecuticals

Phase of Study:	Phase II	Return Visit:	This protocol calls for weekly assesment after discharge during the first 100 days post-transplant. Patients are to return 6 and 12 months after transplant. However, return visits may occur more frequently as clinically indicated.

Treatment Agents:	Busulfan Cyclophosphamide Fludarabine Mesna Mycophenolate Mofetil Tacrolimus	Home Care:	There is no home care as part of this study.

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	Patients are expected to be hospitalized for 5-6 weeks for the transplant. After discharge there is no planned admission unles clinically indicated.

Description/
Intervention:

The goal of this clinical research study is to learn if Cytoxan
(cyclophosphamide) given after busulfan and fludarabine can help to prevent
graft-versus-host disease (GVHD) in patients receiving an allogeneic bone
marrow transplant. This will be tested by comparing up to 3 investigational
therapies for preventing GVHD in patients with leukemia, lymphoma, or multiple
myeloma.

The 3 investigational GVHD prevention therapies that may be tested include
cyclophosphamide alone, cyclophosphamide plus tacrolimus, and cyclophosphamide
plus tacrolimus and mycophenolate mofetil.

Study Objectives / Outcomes

Primary Objective

To determine the optimal regimen of post-grafting immunosuppression with high-dose cyclophosphamide (Cy) following myeloablative conditioning with fludarabine and once-daily intravenous (IV) busulfan and transplantation of fully human leukocyte antigen (HLA)-matched related or unrelated bone marrow that leads to the acceptable incidence of grades III/IV graft-versus-host disease (GVHD) in patients with advanced hematologic malignancies.

Secondary Objectives:

Clinical:

1. To determine the cumulative incidence of nonrelapse mortality (NRM) and Kaplan-Meier estimates of disease-free survival (DFS), and overall survival (OS) measured at 1 year after transplantation

2. To estimate the cumulative incidence of chronic GVHD at 1 year after transplantation.

3. To determine the need for systemic immunosuppressive treatment that needs to be administered beyond the originally planned prophylaxis regimen and duration of its administration.

Laboratory:

1. To characterize immune reconstitution by analyzing peripheral blood mononuclear cells (PBMCs) collected prospectively at defined time points post-transplant.

2. To evaluate busulfan pharmacokinetics and pharmacogenomics and evaluate the feasibility of creating a 6 hour pharmacokinetic sampling schedule.

Study Status Information



Study Activation / Registration Date:	05/29/2009

IRB Review and Approval Date:	10/17/2008

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Open

Projected Accrual:	250

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 must be =/>18 and =/< 65 years of age at time of registration.

2) Patient must have a genotypically HLA-identical sibling, a phenotypically matched first-degree relative or an unrelated donor who is molecularly matched with the patient at HLA-A, B, C, DRB1, and DQB1

3) Patients must have at least one of the following very high-risk conditions listed below: acute lymphocytic leukemia (ALL) in first complete remission (CR) with high risk features defined as evidence of adverse cytogenetics (translocation (9;22), (1;19), or (4;11), or MLL gene rearrangements

4) Acute myeloid leukemia (AML) in CR1 with high risk features defined as: i. Greater than 1 cycle of induction therapy required to achieve remission, ii. Preceding myelodysplastic syndrome (MDS) other than myelofibrosis, secondary AML iii. Presence of Flt3 mutations or internal tandem duplications, iv. FAB M6/M7 classification or adverse cytogenetics for overall survival such as those associated with MDS, M6, M7 leukemia, or v. Complex karyotype [> 3 abnormalities], inv(3), t(3;3), t(6;9), t(6;11), t(11;19)(q23;p13.1), + 8 (alone or with other abnormalities except for t(8:21), t(9;11), inv(16))

5) Acute Leukemias in 2nd or greater CR (CR>2)

6) Refractory or relapsed AML with </= 10% bone marrow blasts and no circulating blasts

7) Chronic myeloid leukemia beyond first chronic phase

8) Chronic myelomonocytic leukemia

9) Philadelphia-negative myeloproliferative disorder

10) Lymphoma: Relapsed chemotherapy-sensitive (complete or partial response) Hodgkin's or Non-Hodgkin's lymphoma

11) Multiple myeloma - stage III

12) Donor eligibility criteria: Donors must be capable of giving informed consent for a standard marrow harvest; mobilized peripheral blood stem cell grafts are not permitted on this protocol. Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Cell Therapy (FACT) and will be screened per the American Association of Blood Banks (AABB) guidelines.

Exclusion Criteria:

1) Prior autologous or allogeneic stem cell transplant.

2) Performance status >2 (ECOG) (See Appendix)

3) Active infection. Protocol PI will be final arbiter if there is uncertainty regarding whether a previous infection is resolved.

4) Left ventricular ejection fraction <45%. No uncontrolled arrhythmias or symptomatic cardiac disease.

5) Symptomatic pulmonary disease. FEV1, FVC, DLCO =/< 50% of predicted (corrected for hemoglobin).

6) Serum creatinine clearance <60 ml/min (calculated with Cockroft-Gault formula). CCr = {[(140 minus age) x IBW (kg)]/PCr x 72 } x 0.85 (for women) PCr x 72

7) Hepatic function: Bilirubin > than 2 times upper normal limits, ALT or AST =/> 3 x laboratory upper normal limits.

8) Positive serology for HIV-1, 2 and HTLV-1, 2.

9) Pregnancy. Female patient must have negative beta-HCG pregnancy test (all women of child bearing-potential must have test performed)

10) Patients that require chronic steroid treatment that cannot be interrupted for 5 days.

Links

Registration Number: NCT00809276
Study Information on Clinical Trials Registry (clinicaltrials.gov)