Thiotepa-based Conditioning for Allogeneic Stem-cell Transplantation (SCT) in Lymphoid Malignancies

Study Overview
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Brief Summary
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The study hypotheses is that the introduction of dose escalated thiotepa, in substitution to busulfan or melphalan, will reduce toxicity after allogeneic transplantation while improving disease eradication in patients with lymphoid malignancies not eligible for standard transplantation.

Official Title
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Phase II Trial of Fludarabine Combined With Intravenous Thiotepa and Allogeneic Hematopoietic Stem-cell Transplantation in Patients With Lymphatic Malignancies Including Multiple Myeloma, Non Hodgkin's, Hodgkin Lymphoma and CLL

Conditions
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Non Hodgkin Lymphoma, Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, Multiple Myeloma

Intervention / Treatment
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* Drug: Thiotepa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age less than physiologic 68 years. Patients with MM, NHL, HL and CLL with an indication for allogeneic transplantation as follows: MM; patients relapsing after autologous transplant or with high-risk cytogenetic abnormalities Aggressive lymphoma and Hodgkin lymphoma; relapse after autologous transplants Follicular lymphoma; failure of at least one prior regimen CLL; failure of prior therapy which includes Fludarabine combinations or 17p- cytogenetic abnormality Patients must have an HLA matched related or unrelated donor willing to donate either peripheral blood stem cells or bone marrow. Matching is based on high-resolution class I (HLA-A, -B, -C) and class II (HLA-DRB1, -DQB) typing. The goal is to transplant > 3 x 106 CD34+ cells per kg body weight of the recipient Patients must sign written informed consent. Adequate birth control in fertile patients. Exclusion Criteria: Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit Creatinine > 2.0 mg/dl ECOG-Performance status > 2 Uncontrolled infection Pregnancy or lactation Abnormal lung diffusion capacity (DLCO < 40% predicted) Severe cardiovascular disease CNS disease involvement Pleural effusion or ascites > 1 liter Known hypersensitivity to Fludarabine or treosulfan Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 68 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: thiotepa<br>Thiotepa 5-10 mg/kg/d x 2 days | Drug: Thiotepa<br>* Chemotherapy given prior to allogeneic stem cell transplantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival | The percentage of patients alive without disease recurrence 2 years after transplant | 2 years after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| treatment-related mortality | The percentage of patients who die of complications related to the transplant | 2 years after transplantation | 
| graft versus host disease | The percentage of patients experiencing graft-versus-host disease after transplant | 1 year after transplantation | 
| relapse | The percentage of patients experiencing disease recurrence after transplant | 2 years after transplantation |