Clinical trial NCT02507479: Thiotepa-based Conditioning for Allogeneic Stem-cell Transplantation (SCT) in Lymphoid Malignancies
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non Hodgkin Lymphoma
Hodgkin Lymphoma
Chronic Lymphocytic Leukemia
Multiple Myeloma
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2015-07-24
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Age less than physiologic 68 years.
2. Patients with MM, NHL, HL and CLL with an indication for allogeneic transplantation as follows:

   1. MM; patients relapsing after autologous transplant or with high-risk cytogenetic abnormalities
   2. Aggressive lymphoma and Hodgkin lymphoma; relapse after autologous transplants
   3. Follicular lymphoma; failure of at least one prior regimen
   4. CLL; failure of prior therapy which includes Fludarabine combinations or 17p- cytogenetic abnormality
3. 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
4. Patients must sign written informed consent.
5. Adequate birth control in fertile patients.

Exclusion Criteria:

1. Bilirubin \> 3.0 mg/dl, transaminases \> 3 times upper normal limit
2. Creatinine \> 2.0 mg/dl
3. ECOG-Performance status \> 2
4. Uncontrolled infection
5. Pregnancy or lactation
6. Abnormal lung diffusion capacity (DLCO \< 40% predicted)
7. Severe cardiovascular disease
8. CNS disease involvement
9. Pleural effusion or ascites \> 1 liter
10. Known hypersensitivity to Fludarabine or treosulfan
11. Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate

Primary outcomes:
measure: disease-free survival
timeFrame: 2 years after transplantation
Secondary outcomes:
measure: treatment-related mortality
timeFrame: 2 years after transplantation
measure: graft versus host disease
timeFrame: 1 year after transplantation
measure: relapse
timeFrame: 2 years after transplantation
Other outcomes:
Locations:
city: Tel-Hashomer
country: Israel
facility: Chaim Sheba Medical Center
city: Tel-Hashomer
country: Israel
facility: Chaim Sheba Medical Center
Study officials:
affiliation: Chaim Sheba Medical Center
name: Arnon Nagler, MD
role: PRINCIPAL_INVESTIGATOR
References: