Reduced Intensity Haploidentical Transplant for Hematological Malignancies

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

Many patients with hematological malignancies (leukemia, lymphoma, multiple myeloma) cannot undergo hematopoietic stem cell transplantation (HSCT) because they do not have a well matched donor. HSCT from partially matched family donors (haploidentical HSCT) is an option for most patients but has been associated with poor outcomes. This study was designed to test whether using an exact amount of a donor's lymphocytes (white cells) and dividing the transplant process into 2 steps, would increase overall survival by decreasing complications. The therapy is reduced intensity so it is targeted, but not limited to, patients over the age of 65 or those who have had previous transplants.

Study Overview

• Status: Completed
• Conditions: Hematological Malignancies
• Intervention / Treatment: Device: Haploidentical Allogeneic Transplantation

Detailed Description

Haploidentical hematopoietic stem cell transplant is a life saving therapy for patients who are without well matched donors. This type of therapy has been associated with poor outcomes in the past due to complications such as infection. The Jefferson 2 Step approach was designed to allow the infusion of an exact dose of tolerized lymphocytes in haploidentical transplant in order to allow for immune reconstitution post transplant to avoid infectious complications while still having acceptable rates of GVHD. In this approach, older patients or patients who were transplanted previously with high-risk hematological malignancies undergo chemotherapy with fludarabine and cytarabine or thiotepa. The patients then receive an exact dose of their donors' lymphocytes. The phase I portion of the study determined the optimal dose of lymphocytes. Two days after receiving the donor lymphocytes, the patients receive 2 daily doses of cyclophosphamide. The purpose of the cyclophosphamide is for in-vivo tolerization of the lymphocytes. One day after receiving cyclophosphamide, the patients receive stem cell from their donor. Tacrolimus and mycophenolate mofetil are used as GVHD prophylaxis.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2; Phase 1

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.
2. Patients must have a related donor who is a two or more allele mismatch at the HLA-A;B; C; DR loci.
3. Patients who have sibling donors with a one antigen mismatch due to recombination will not be enrolled in this protocol.

4. Patients must adequate organ function:

   1. LVEF of >45%
   2. DLCO >45% of predicted corrected for hemoglobin
   3. Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X upper limit of normal
   4. Serum creatinine < 2.0 mg/dl or creatinine clearance of > 40 ml/min
5. Performance status > 70% (Karnofsky)
6. Patients must be willing to use contraception if they have childbearing potential
7. Able to give informed consent

Exclusion Criteria:

1. Performance status of < 70% (Karnofsky)
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 or complications there from.
7. Patients who have received alemtuzumab within 8 weeks of transplant admission, or who have recently received horse or rabbit anti-thymocyte globulin and have ATG levels of > 2 µgm/ml.
8. Patients who cannot receive cyclophosphamide
9. Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol

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: Transplantation	Device: Haploidentical Allogeneic Transplantation; Patients undergoing reduced intensity haploidentical hematopoietic stem cell transplant from a partially matched related donor.; Other Names: CliniMACS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival at 6 Months Post-transplant in Patients Receiving a Partially-matched Related Donor Allogeneic Transplant After Reduced-intensity Conditioning	Number of patients alive at 6 months post-transplant	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Successful Engraftment	6 months
Immune Reconstitution	Up to 5 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Investigators: Principal Investigator: Neal Flomenberg, MD, 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: September 1, 2006
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: July 12, 2010
• First Submitted That Met QC Criteria: July 12, 2010
• First Posted (Estimated): July 14, 2010

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Reduced Intensity Haploidentical Transplant
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: 06U.328; 2006-29 (Other Identifier: CCRRC); JT 1149 (Other Identifier: JeffTrial Number)