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

Phase 2

Terminated

• Conditions: Multiple Myeloma; Waldenstroms; CLL / SLL; Non Hodgkin's Lymphoma; Mantle Cell Lymphoma
• Interventions: Drug: Fludarabine; Radiation: Total Body Irradiation; Other: Infusion of Stem Cells

• Registration Number: NCT00714259
• Lead Sponsor: University of Alabama at Birmingham

Brief Summary

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

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.

Study Timeline

• Study Start: 2008-07
• Study First Submitted: 2008-07-10
• Study First Submitted QC: 2008-07-11
• Study First Posted: 2008-07-14
• Primary Completion: 2013-02
• Study Completion: 2013-02
• Results First Submitted: 2015-11-05
• Results First Submitted QC: 2017-03-23
• Results First Posted: 2017-05-04
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-22
• Last Update Posted: 2017-07-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Non Myeloablative Treatment	Fludarabine	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.
Non Myeloablative Treatment	Total Body Irradiation	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.
Non Myeloablative Treatment	Infusion of Stem Cells	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.

Primary Outcome Measures

Name	Time	Method
Progressive Free Survival Post Transplant	365 days 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.
Progression Free Survival Post Transplant	2 years 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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Detectable Donor Chimerism at up to 100 Days Post Transplant	Post transplant 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.
Composite Incidence of Acute and Chronic Graft Versus Host Disease	Up to 100 days post transplant.
Non-relapse Treatment Related Mortality	Within 100 days post transplant	Death related to treatment without relapse within 100 days after transplant

Trial Locations

Locations (1)

University of Alabama in Birmingham BMT/CT Program Outpatient Clinic; 🇺🇸 Birmingham, Alabama, United States