Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk Hematologic Malignancies Using One Haploidentical Donor

NCT01982682 | Completed Phase 2 Results DMC

• 3 other identifiers: 13D.3522013-031JT 2974
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well total-body irradiation, donor lymphocyte infusion, and cyclophosphamide before donor stem cell transplant works in treating patients with high-risk hematologic malignancies. Giving total-body irradiation, donor lymphocyte infusion, and chemotherapy before a donor stem cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When certain stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant and giving tacrolimus and mycophenolate mofetil may stop this from happening.

Conditions

Hematopoietic/Lymphoid Cancer

Outcome Measures

Primary Outcomes (1)

• Count of Participants That Experience 1 Year Relapse Free Survival After Undergoing Hematopoietic Stem Cell Transplantation (HSCT) Using the Thomas Jefferson University 2 Step Approach

  Up to 1 year after HSCT

Secondary Outcomes (4)

• Number of Participants With Successful Engraftment

  Up to 1 year after HSCT

• Count of Participants That Experienced Death as a Result of Graft-versus-host Disease (GVHD)

  Up to 1 year after HSCT

• Median Pace of T Cell Immune Recovery at 28 Days Post Hematopoietic Stem Cell Transplantation (HSCT)

  At 28 days post HSCT

• Median Pace of T Cell Immune Recovery at 90 Days Post Hematopoietic Stem Cell Transplantation (HSCT)

  90 days post HSCT

Study Arms (1)

Treatment (TBI, DLI, cyclophosphamide, CD34+ donor HSCT)

EXPERIMENTAL

CONDITIONING REGIMEN: Patients undergo TBI BID on days -10 to -8, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANT: Patients undergo CD34+ (cluster of differentiation 34+) selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning by day 42, and mycophenolate mofetil IV BID on days -1 to 28.

Radiation: Total-Body Irradiation (TBI); Biological: Donor Lymphocyte Infusion (DLI); Drug: Cyclophosphamide; Procedure: Allogeneic hematopoietic stem cell transplantation (HSCT); Drug: Mycophenolate mofetil

Interventions

Total-Body Irradiation (TBI) RADIATION

Undergo TBI

Treatment (TBI, DLI, cyclophosphamide, CD34+ donor HSCT)

Donor Lymphocyte Infusion (DLI) BIOLOGICAL

Undergo DLI

Treatment (TBI, DLI, cyclophosphamide, CD34+ donor HSCT)

Cyclophosphamide DRUG

Given IV

Also known as: Endoxan, Cytoxan, Neosar, Procytox, Revimmune, cytophosphane, Lyophilizedcytoxan

Treatment (TBI, DLI, cyclophosphamide, CD34+ donor HSCT)

Allogeneic hematopoietic stem cell transplantation (HSCT) PROCEDURE

Undergo CD34+ selected allogeneic HSCT

Treatment (TBI, DLI, cyclophosphamide, CD34+ donor HSCT)

Mycophenolate mofetil DRUG

Given IV

Also known as: CellCept

Treatment (TBI, DLI, cyclophosphamide, CD34+ donor HSCT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• This treatment is for patients with high risk hematologic malignancies. High risk is defined as:
• Any patient with a hematologic malignancy with residual disease after treatment with 1 or more chemotherapy regimens in whom achievement of remission with additional chemoradiotherapy is felt to be unlikely
• Patients without morphologic evidence of disease but with high risk features which would predict for relapse despite remission at HSCT such as adverse cytogenetics, 3rd or greater CR (complete response), or failure to recover peripheral blood counts to normal ranges. While these patients do not have detectable disease by current methods, like all patients they have non-detectable disease which in their case is highly aggressive.
• Patients must have one related donor who is HLA (human leukocyte antigen) mismatched in the GVHD direction at two or more HLA loci
• Patients must adequate organ function:
• LVEF (left ventricular ejection fraction) of \>50 %
• Diffusing capacity of the lungs for carbon monoxide (DLCO) (adjusted for hemoglobin) \>50 % of predicted and forced expiration to the full FEV-1 \>50 %
• Adequate liver function as defined by a serum bilirubin \<1.8, AST (aspartate aminotransferase) or ALT (alanine aminotransferase) \< 2.5X upper limit of normal
• Creatinine clearance of \> 60 ml/min
• Karnofsky Performance Status (KPS) of \> 80% on the modified (KPS) tool
• Patients must be willing to use contraception if they have childbearing potential
• Able to give informed consent

You may not qualify if:

• Modified (KPS) Karnofsky Performance status of \<80%
• \> 5 Comorbidity Points on the Hematopoietic cell transplantation - specific comorbidity (HCT-CI) Index (See Appendix B)
• Class I or II antibodies against donor human leukocyte antigens (HLA)
• HIV positive
• Active involvement of the central nervous system with malignancy
• Psychiatric disorder that would preclude patients from signing an informed consent
• Pregnancy, or unwillingness to use contraception if they have child bearing potential
• Patients with life expectancy of \< 6 months for reasons other than their underlying hematologic/oncologic disorder
• Alemtuzumab treatment within 8 weeks of HSCT admission
• Anti-thymocyte globulin (ATG) level of \> 2 ugm/ml
• Patients with active inflammatory processes including T max \>101 or active tissue inflammation are excluded
• Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses specified in the treatment plan

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Thomas Jefferson University Hospitals

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Whole-Body Irradiation; Cyclophosphamide; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Dr. Dolores Grosso
• Organization: Sidney Kimmel Cancer Center at Thomas Jefferson University

dolores.grosso@jefferson.edu

215-955-0182

Study Officials

• Dolores Grosso, DNP, CRNP

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2013
• First Posted: November 13, 2013
• Study Start: November 4, 2013
• Primary Completion: March 27, 2017
• Study Completion: March 27, 2017
• Last Updated: April 30, 2025
• Results First Posted: June 7, 2018

Record last verified: 2025-04

Locations

US (1)