A Study of Bone Marrow Transplantation Using Fully-Matched Relatives as Donors for Patients With Hematological Malignancies

A Two Step Approach To Matched-Sibling Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk Hematological Malignancies

This research study uses a drug called cyclophosphamide to decrease the incidence of GVHD in matched sibling hematopoietic stem cell transplant. In doing so, the goal of the study is to increase overall survival.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Leukemia; Multiple Myeloma; Hematological Malignancies; Hodgkin's Disease
• Intervention / Treatment: Device: Matched Sibling Allogeneic Transplantation

Detailed Description

This research protocol has been developed for patients undergoing matched-sibling hematopoietic stem cell transplant (HSCT). The patients who are treated according to this 2 step allogeneic HSCT protocol will receive cyclophosphamide to induce in-vivo tolerization of both autologous and allogeneic lymphocytes, followed by an allogeneic CD34-selected HSCT. The primary research questions relate to immune reconstitution, incidence of GVHD, and relapse in patients who receive lymphocyte treatment of this type in allogeneic HSCT and how it impacts overall survival.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Any patient with a hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. Patients will be considered high-risk if they have any of the following:

   1. Age > 50 years
   2. ECOG Performance status of <2
   3. Acute leukemia: requiring more than one chemotherapy regimen to obtain 1st CR; second or greater CR, 1st relapse; any ph+ ALL
   4. CML 2nd chronic phase, accelerated phase, or blastic phase
   5. MDS with IPS of Intermediate 2 or greater
   6. Any myeloproliferative disorder
   7. Hodgkin lymphoma: relapsed, refractory, or primary induction failure
   8. Non-Hodgkin lymphoma: relapsed, refractory, primary treatment failure, or not eligible for an autologous HSCT
   9. Other conditions not listed will be assessed as high-risk by the PI
2. Patients must have a related donor who is either HLA-identical or a one antigen mismatch at the HLA- A; B; C; and DR loci.

3. Patients must adequate organ function:

   1. LVEF of >45%
   2. DLCO (adjusted for hemoglobin) >45% of predicted
   3. Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X upper limit of normal
   4. Creatinine clearance of > 60 ml/min
4. Patients must be willing to use contraception if they have childbearing potential
5. Able to give informed consent

Exclusion Criteria:

1. ECOG performance status of 3 or 4.
2. HIV positive
3. Active involvement of the central nervous system with malignancy
4. Psychiatric disorder that would preclude patients from signing an informed consent
5. Pregnancy
6. Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder.

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: Allogeneic Transplantation; Matched Sibling Allogeneic Transplantation	Device: Matched Sibling Allogeneic Transplantation; Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization; Other Names: CliniMACS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Overall Survival	The primary objective of this prospective, phase II trial was to obtain an OS rate of >60% at 1 year in patients undergoing a 2 step HSCT from an HLA compatible family donor. The >60% threshold was selected as a composite efficacy measure as patients with any hematologic diagnosis, stage of disease, or age as old as 65 years were eligible for this treatment protocol.	1 Year after transplant

Secondary Outcome Measures

Outcome Measure	Time Frame
Graft Versus Host Disease (GVHD)	1 Year after transplant

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
• Investigators: Principal Investigator: Neal Flomenberg, MD, Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Publications and helpful links

Helpful Links

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospitals

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2008
• Primary Completion (Actual): September 19, 2018
• Study Completion (Actual): August 29, 2019

Study Registration Dates

• First Submitted: March 11, 2011
• First Submitted That Met QC Criteria: March 11, 2011
• First Posted (Estimated): March 15, 2011

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: lymphoma; multiple myeloma; leukemia; Hodgkin's Disease; Hematological malignancies; Myeloablative Hematopoietic Stem Cell Transplant; Cyclophosphamide tolerization; 2 Step Approach
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms by Site; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Leukemia; Hematologic Neoplasms; Lymphoma; Multiple Myeloma; Hodgkin Disease
• Other Study ID Numbers: 08D.85; 2007-61 (Other Identifier: CCRRC); JT 1275 (Other Identifier: JeffTrial Number)