Allogeneic Hematopoietic Stem Cell Transplantation With Reduced Intensity Pre-transplant Conditioning for the Treatment of High-risk Hematological Malignancies (V3)

Allogeneic Hematopoietic Stem Cell Transplantation With Reduced-Intensity Pre-Transplant Conditioning for the Treatment of High-Risk Hematological Malignancies

This is study is for patients that have been diagnosed with high-risk hematological malignancies. The main purpose of this study is to confirm previously published results of stem cell transplantation with reduced intensity pre-transplant conditioning. Patients will be assigned to 1 of 3 regimens depending on the patient's diagnosis. Participants will be followed by the transplant team for the remainder of the patient's life. Patient's will visit MUSC daily, then visits will be reduced to frequent visits for up to 6 months. After 6 months, the visits will be reduced more depending on the patient's condition.

Study Overview

• Status: Terminated
• Conditions: Hematological Malignancies
• Intervention / Treatment: Drug: Regimen A; Drug: Regimen B; Drug: Regimen C

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A proven diagnosis of one of the conditions in Table 1.
• Prior therapy including blood or marrow transplant will not exclude patients for reduced intensity transplant.
• Age < 75 years. Pediatric patients are eligible from the ages of 1 month to 18 years if the transplant physician believes that co-morbid conditions significantly increase the risk for a standard transplant regimen.
• HIV antibody negative.
• ECOG performance status 0-3, (or equivalent Karnofsky and Lansky performance scores for patients <18yrs, see appendix 2)
• Availability of an HLA-identical related donor or suitable alternative donor, (≥7/8 allele match at A, B, C and DRB). Syngeneic transplants will not be allowed in this protocol.
• Due to the complexity of the study, all patients prior to enrollment will be assessed by the PI or co-PI.
• Patient with marrow failure states or immune deficiency syndromes undergoing stem cell transplants must be reviewed by one of the investigators to determine eligibility for study.
• Adequate insurance coverage (or financial resources) to cover the costs associated with the patient's transplant and, in the case of patients eligible for cohort C, to cover the costs associated with I 131 Tositumomab treatment.

Exclusion Criteria:

• Active CNS involvement with malignant disease.
• Pregnancy.
• Fertile men or women unwilling to use contraceptive techniques during the study period.
• Creatinine clearance < 30 ml/min.
• Left ventricular ejection fraction <30% or clinical cardiac failure uncontrolled by medical therapy.
• Pulmonary disease requiring supplemental oxygen therapy.
• Patients with estimated life span less than 1 year due to medical illnesses other than the condition being treated on the study.

Donor Selection:

Inclusion Criteria

• Major HLA identical relative or genotypically matched unrelated donor (7-8/8 alleles) .
• Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Cell Therapy (FACT) and will be screened per the American Association of Blood Banks (AABB) guidelines.

Exclusion Criterion

• Positive anti-donor HLA antibody.
• Identical twin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm, non-randomized study	Drug: Regimen A; Chronic Lymphocytic Leukemia/ Chronic Prolymphocytic Leukemia, Multiple Myeloma.; Drug: Regimen B; Other malignancies not addressed in A or C; Drug: Regimen C; B-Cell Lymphomas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Determine the Treatment-related Mortality Rate of Allogeneic Stem Cell Transplants Using Reduced-intensity Conditioning Regimens Within 1st 100-days.	Number of subject deaths prior to day 100.	8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Determine the Engraftment Rate of Allogeneic Stem Cell Transplants	To determine the engraftment rate of allogeneic stem cell transplants using reduced-intensity conditioning regimens. It will be measured as the proportion of subjects meeting criteria for engraftment before day +30 and full donor chimerism demonstrated before or at day +100. Engraftment is defined by maintenance of ANC > 500/mm3 for at least 3 consecutive days and platelet count > 20,000/mm3 for 3 consecutive days in absence of platelet transfusion. These criteria must have been met before Day +30. Chimerism is the pressence of donor cells and will be analyzed by FISH for sex-mismatched donor-recipient pairs and VNTR analysis for sex-mathced pairs. Chimerism by Day +100 will be documented for this outcome	Day +100
Morbidity of Allogeneic Stem Cell Transplants	To determine the morbidity, including the pattern and severity of complications, of allogeneic stem cell transplants using reduced-intensity conditioning regimens. The average number of days spent in the hospital until day +100 will be reported as a surrogate for morbidity and complications.	100 days

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Principal Investigator: Robert Stuart, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: June 4, 2010
• First Submitted That Met QC Criteria: June 7, 2010
• First Posted (Estimate): June 8, 2010

Study Record Updates

• Last Update Posted (Actual): July 11, 2018
• Last Update Submitted That Met QC Criteria: June 13, 2018
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: high-risk hematological malignancies
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: 101370; HR#19490 (Other Identifier: MUSC IRB)