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

NCT00185796 | Completed Phase 2

• 4 other identifiers: BMT16895130NCT0018579613680
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Myeloproliferative Disorders; Blood Cancer; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (2)

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

  7/15/2017

• 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.

  7/15/2017

Secondary Outcomes (5)

• To evaluate myeloid and platelet engraftment.

  7/15/2017

• To evaluate the incidence of acute and chronic GVHD.

  7/15/2017

• To evaluate the rate of primary and secondary graft failure.

  7/15/2017

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

  7/15/2017

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

  7/15/2017

Study Arms (1)

TLI/ATG conditioning

EXPERIMENTAL

Lymphoid irradiation and anti-thymocyte globulin (TLI/ATG).

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

Interventions

Total Lymphoid Irradiation (TLI) PROCEDURE

TLI is administered ten times in 120cGy fractions on day -11 through day -7 and day -4 through day -1

TLI/ATG conditioning

Anti-Thymocyte Globulin as Conditioning (ATG) PROCEDURE

Thymoglobulin will be administered five times intravenously at 1.5 mg/kg/day from day -11 through day -7 for a total dose of 7.5 mg/kg. Thymoglobulin doses will be based on the adjusted ideal body weight if the patient is greater than or equal to 15 kg over ideal body weight.

TLI/ATG conditioning

Eligibility Criteria

• Age: 49 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Organ dysfunction as defined by the following:
• 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%.
• 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.
• Identical twin

Sponsors & Collaborators

• Stanford University: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Hematologic Neoplasms; Myelodysplastic Syndromes

Interventions

Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• Robert Lowsky

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 16, 2005
• Study Start: July 1, 2004
• Primary Completion: April 1, 2014
• Study Completion: February 1, 2015
• Last Updated: March 18, 2015

Record last verified: 2015-03

Locations

US (1)