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TLI & ATG for Non-Myeloablative Allogeneic Transplantation for MDS and MPD

Information source: Stanford University
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Myeloproliferative Disorders; Blood Cancer; Myelodysplastic Syndromes

Intervention: Total Lymphoid Irradiation (TLI) (Procedure); Anti-Thymocyte Globulin as Conditioning (ATG) (Procedure)

Phase: Phase 2

Status: Completed

Sponsored by: Stanford University

Official(s) and/or principal investigator(s):
Robert Lowsky, Principal Investigator, Affiliation: Stanford University

Summary

To evaluate the feasibility and safety of TLI/ATG conditioning for allogeneic HCT for elderly patients with advanced stage MDS and MPD.

Clinical Details

Official title: Total Lymphoid Irradiation and Anti-Thymocyte Globulin as Conditioning for Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation for the Treatment of Myelodysplastic Syndromes and Myeloproliferative Disorders (Except CML)

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

Primary outcome:

To improve survival outcome for selected patients with advanced stages of MDS and MPD with non-myeloablative allogeneic HCT from related and unrelated donors.

To evaluate the feasibility and safety of TLI/ATG conditioning for allogeneic HCT for elderly patients or those with co-morbid conditions that preclude myeloablative transplantation for advanced stage MDS and MPD.

Secondary outcome:

To evaluate myeloid and platelet engraftment.

To evaluate the incidence of acute and chronic GVHD.

To evaluate the rate of primary and secondary graft failure.

To evaluate the rate of relapse, survival and event-free survival.

To evaluate if DLI can be used safely in patients with mixed chimerism.

Detailed description: Total Lymphoid Irradiation and Anti-Thymocyte Globulin as Conditioning for Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation for the Treatment of Myelodysplastic Syndromes and Myeloproliferative Disorders (except CML). To evaluate the feasibility and safety of TLI/ATG conditioning for allogeneic HCT for elderly patients or those with co-morbid conditions that preclude myeloablative transplantation for advanced stage MDS and MPD.

Eligibility

Minimum age: 49 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria: GENERAL INCLUSION CRITERIA

- General inclusion criteria must include at least one of the following:

- Patients aged > 49 and < 75 years with MDS or MPD

- Patients aged < 49 years at high risk for regimen related toxicity using

standard high dose regimens. Factors considered high risk include pre-existing conditions such as a chronic disease affecting kidneys, liver, lungs, or heart.

- Patients with secondary MDS following a prior autologous transplant.

- An HLA-identical related or an HLA-matched unrelated donor is available. ABO

incompatibility is acceptable.

- A signed informed consent form.

MYELODYSPLASTIC SYNDROME CRITERIA

- Diagnosis of MDS classifiable by the FAB system as refractory anemia (RA), refractory

anemia with ringed sideroblasts (RARS), chronic myelomonocytic leukemia (CMML), refractory anemia with excess blasts (RAEB), and MDS transformed to acute leukemia.

- Patients with advanced MDS must be cytoreduced to < 10% marrow blasts prior to

receiving conditioning with TLI/ATG. Less than 10% marrow blasts must be documented by marrow examination within 1 month of starting conditioning. The cytoreductive regimen will be determined by referring centers.

- Patients with evolution to AML are required to be in a complete remission as defined

by a blast count of less than 5% in a marrow aspirate with adequate cellularity. Presence of residual dysplastic features following cytoreductive therapy is acceptable.

- All patients with high risk disease, for example "intermediate-2" or "high risk"

disease by the IPSS score. Other selected patients with a lower IPSS score may be considered but only after discussion with the BMT attending physicians, as a group, and the PI of the study. MYELOPROLIFERATIVE DISORDERS

- Myeloproliferative disorders to be included:

- Philadelphia chromosome-negative CML.

- Patients with polycythemia vera with persistent thrombotic or hemorrhagic

complications despite conventional therapy, or who have progressed to post-polycythemic marrow fibrosis.

- Patients with essential thrombocythemia with persistent thrombotic or

hemorrhagic complications despite conventional therapy, or who have progressed to myelofibrosis.

- Patients with agnogenic myeloid metaplasia with high risk disease, for example

"intermediate" or "high risk" according to the Lille Scoring System.

- Patients must be cytoreduced to < 10% marrow blasts. Less than 10% marrow blasts must

be documented by marrow examination within 1 month of initiation of TLI/ATG. The cytoreductive regimen will be determined by referring centers.

- Patients with evolution to AML are required to be in a complete remission as defined

by a blast count of less than 5% in a marrow aspirate with adequate cellularity. Presence of residual dysplastic features following cytoreductive therapy is acceptable.

INCLUSION CRITERIA - RELATED DONORS

- Related to the patient and is genotypically or phenotypically HLA-identical.

- Donor age < 75 unless cleared by P. I

- Capable of giving written, informed consent.

- Donor must consent to PBSC mobilization with G-CSF and apheresis

INCLUSION CRITERIA - UNRELATED DONORS

- Donors must be HLA-matched as defined by the following criteria:

- Matched for HLA-DRB1 and DQB1 by high resolution typing.

- Serologic match for all recognized HLA-A, HLA-B, and HLA-C antigens, and

molecular match for at least 5 of 6 HLA-A, HLA-B, or HLA-C antigens by high resolution typing.

- Donor must consent to PBSC mobilization with G-CSF and apheresis. Bone marrow

unrelated donors are not eligible for this protocol. Exclusion Criteria: GENERAL EXCLUSION CRITERIA

- Organ dysfunction as defined by the following:

- Renal: Patients with a normal creatinine are eligible for study without the need

for a 24 hr urine collection for creatinine clearance. Patients with an elevated creatinine require a 24 hr urine collection. If the creatinine clearance is < 50 ml/min patients will be determined for inclusion on a case by case basis.

- Cardiac: Ejection fraction < 40%, symptomatic congestive heart failure requiring

therapy, poorly controlled cardiac arrythmias, or poorly controlled hypertension with inability to maintain a steady-state blood pressure of 150/90.

- Pulmonary: Requirement for supplemental oxygen administration, or pulmonary

function testing showing (1) DLCO < 50% of predicted, (2) TLC < 30%, or (3) FEV1 < 30%.

- Hepatic: Patients with clinical or laboratory evidence of liver disease would be

evaluated for the cause of liver disease, its clinical severity in terms of liver function and degree of portal hypertension. Patients will be excluded if they are found to have fulminant liver failure, cirrhosis if the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess. Biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dl, and symptomatic biliary disease.

- Bone marrow documenting blast count >=10%.

- Presence of active of non-hematologic malignancy (except localized non-melanoma skin

malignancies) or hematologic malignancy other than MDS or MPD as listed in inclusion criteria.

- Active CNS involvement of disease.

- Karnofsky performance score <= 60% or Lansky-Play Performance score <50 for pediatric

patients.

- Life expectancy severely limited by diseases other than malignancy.

- Fungal infections with radiological progression despite with an amphotericin product

or active triazole for > 1 month.

- Active bacterial infection.

- Patients of fertile age who refuse contraception for a twelve month period

post-transplant.

- Pregnant or lactating females.

- HIV seropositivity.

- Severe psychological illness.

EXCLUSION CRITERIA - RELATED DONORS

- Identical twin

- Any contra-indication to the administration of subcutaneous G-CSF at a dose of

16mg/kg/d for five consecutive days

- Serious medical or psychological illness

- Pregnant or lactating females

- Prior malignancy within the preceding five years, with the exception of non-melanoma

skin cancers.

- HIV seropositivity

Locations and Contacts

Stanford University School of Medicine, Stanford, California 94305, United States
Additional Information

Starting date: July 2004
Last updated: March 16, 2015

Page last updated: August 20, 2015

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