Non-Myeloablative Allogeneic HSCT From HLA Matched Related or Unrelated Donors for the Treatment of Low Grade B Cell Malignancies

Study Overview
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Brief Summary
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A non-myeloablative treatment strategy and uniform selection criteria will enable patients with a variety of low grade B-Cell malignancies to attain long term disease control without unacceptably high treatment related mortality.

Detailed Description
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Non myeloablative transplant aims to achieve the immunological advantage of graft versus tumor effect as conventional myeloablative therapy without causing high treatment related toxicities. Non myeloablative transplant has been gaining wider acceptance as a way to achieve longer disease free and over all survival in patients with low grade B-cell malignancies, which otherwise is an incurable disease. Recent studies of non-myeloablative HSCT have demonstrated the powerful effect of graft versus leukemia alone against myeloma and other malignant B-cell malignancies if the transplant is performed for low grade, low volume disease.

Official Title
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UAB 0775 Phase II Trial of Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation Protocol From HLA Matched Related Donors for The Treatment of Patients With Low Grade B Cell Malignancies

Conditions
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Multiple Myeloma, CLL / SLL, Non Hodgkin's Lymphoma, Waldenstroms, Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: Fludarabine
* Radiation: Total Body Irradiation
* Other: Infusion of Stem Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage II or III non-progressive disease Multiple Myeloma. CLL/SLL, and low grade Hodgkin Lymphomas that are in a very good partial response or complete response with non-progressive disease. ≤ 70 years old. Eligible and willing HLA matched related donor. Bilirubin <2xULN. ALT and AST <3xULN. LVEF > 40%. Creatinine Clearance >40mL/min. Pulmonary function DLCO corrected to ≥ 70%. Minimum performance score of 70%. Platelet count >130 x103 micro L. LDH ≤1.5xULN. No proceeding co-morbid condition that significantly increases the risk of severe regimen related toxicity. No uncontrolled infections. Exclusion Criteria: Age >70 years old. Performance status <70%. Uncontrolled infections or is HIV positive Prior malignancies that are felt to have a <80% probability of being cured. Pregnant, breastfeeding, or refuse to use contraceptive techniques during and for 12 months following transplant. Prior Allograft History of rapidly growing disease at diagnosis or at any progression or have MDS. No eligible and willing HLA matched donor.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Other: Non Myeloablative Treatment<br>Non-myeloablative Transplant Conditioning Chemotherapy : Fludarabine - 30 mg/m2/day x 3 days Total Body Irradiation - 200cGy x1 dose Infusion of Stem Cells - On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10*6 CD34+ cells per kilogram of recipient weight. | Drug: Fludarabine<br>* Fludarabine 30 mg/m2/day x 3 days<br>Radiation: Total Body Irradiation<br>* TBI 200cGy x1 dose on transplant day<br>Other: Infusion of Stem Cells<br>* On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10*6 CD34+ cells per kilogram of recipient weight.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progressive Free Survival Post Transplant | subjects surviving without disease progression at 100 days after transplant as evidenced by decreased disease and no new disease showing on radiologic scans and / or bone marrow pathology. | 100 days post transplant | 
| Progressive Free Survival Post Transplant | Subjects surviving without disease progression 180 days after transplant as evidenced by decreased disease and no new disease showing on radiologic scans and / or bone marrow pathology. | 180 days post transplant | 
| Progressive Free Survival Post Transplant | Subjects surviving without disease progression 365 days after transplant as evidenced by decreased disease and no new disease showing on radiologic scans and / or bone marrow pathology. | 365 days post transplant | 
| Progression Free Survival Post Transplant | Subjects surviving without disease progression 2 years after transplant as evidenced by no new disease showing on radiologic scans and / or bone marrow pathology. | 2 years post transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-relapse Treatment Related Mortality | Death related to treatment without relapse within 100 days after transplant | Within 100 days post transplant | 
| Number of Participants With Detectable Donor Chimerism at up to 100 Days Post Transplant | Measured by number of participants that have chimerism study results that show the number of donor cells and the number of recipient cells present in the blood after post-transplant lymphocyte infusions continue to be predominately either donor or recipient. | Post transplant up to 100 days post transplant | 
| Composite Incidence of Acute and Chronic Graft Versus Host Disease |  | Up to 100 days post transplant. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low Grade B Cell Malignancies, nonmyeloablative transplant, allogeneic