A Research Study of Bone Marrow Transplantation From Unrelated or Partially Matched Related Donors

NCT01349101 | Completed Phase 2 Results DMC

• 3 other identifiers: 11D.512010-54JT 2137
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

It is hypothesized that engraftment when administering cyclophosphamide post the stem cell infusion will increase, the incidence of graft versus host disease (GVHD) and day 100 mortality will decrease, and the use of cyclophosphamide post stem cell infusion with alternative donors will be as safe and as effective as traditional matched transplants.

Conditions

Hematological Malignancies

Keywords

hematopoietic stem cell transplantation; HSCT; allogeneic marrow transplantation; cyclophosphamide; graft-versus-host disease; GVHD

Outcome Measures

Primary Outcomes (1)

• Successful Engraftment Using Cyclophosphamide Post-Transplant

  Successful Hematopoietic engraftment will be assessed by determining the incidence of participants who achieve both of the following criteria within the 100 days post-transplant: ANC \>/= 0.5x10e9/L for at least 3 days. Platelet engraftment \>20,000 with no transfusions X 7 days. The incidence will be calculated as the number of participants who meet both engraftment criteria. Results will be presented as a proportion/percentage/probability not as an incidence rate.

  Through 100 days post-transplant

Secondary Outcomes (3)

• Cumulative Incidence of Grade III-IV GVHD

  Through 100 days post-transplant

• Incidence of GVHD Unresponsive to Corticosteroids and Photopheresis

  Through 100 days post-treatment

• Transplant-Related Mortality

  100 days post-transplant

Study Arms (2)

Myeloablative HSCT

EXPERIMENTAL

Myeloablative Hematopoietic Stem Cell Transplantation (HSCT): Patients will receive myeloablative transplants or nonmyeloablative transplants depending on their disease type.

Radiation: Total Body Irradiation; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate mofetil; Genetic: Hematopoietic stem cell transplantation

Reduced Intensity HSCT

EXPERIMENTAL

Reduced Intensity Hematopoietic Stem Cell Transplantation (HSCT): Patients who have received a previous transplant, patients who have received dose limiting radiation, and patients with a DLCO \<45% will receive the reduced intensity conditioning regimen.

Radiation: Total Body Irradiation; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate mofetil; Drug: Fludarabine; Drug: Busulfan; Genetic: Hematopoietic stem cell transplantation

Interventions

Fludarabine DRUG

Started the fifth day before the transplant. Given for four days at 30 mg/m2/d.

Also known as: fludarabine phosphate, Fludara

Reduced Intensity HSCT

Busulfan DRUG

Started the fourth day before the transplant. Given for two days at 3.2 mg/kg.

Also known as: Myleran, Busulfex IV

Reduced Intensity HSCT

Hematopoietic stem cell transplantation GENETIC

Allogeneic marrow transplantation given after the last dose of total body irradiation (TBI)

Also known as: HSCT

Myeloablative HSCT; Reduced Intensity HSCT

Total Body Irradiation RADIATION

Myeloablative HSCT Arm: Total body irradiation (TBI) is given in 8 fractions over 4 days (total dose of 12 Gy) Reduced Intensity HSCT Arm: TBI is given in one fraction (total dose of 2 Gy)

Also known as: TBI, radiotherapy

Myeloablative HSCT; Reduced Intensity HSCT

Cyclophosphamide DRUG

Cyclophosphamide is administered on the third day after the hematopoietic stem cell transplantation (HSCT) to help reduce graft-versus-host disease (GVHD). It is given at a dose of 60 mg/kg/d for 2 days on days +3 and +4.

Also known as: Endoxan, Cytoxan, Neosar, Procytox, Revimmune, Cytophosphane, Cy

Myeloablative HSCT; Reduced Intensity HSCT

Tacrolimus DRUG

Started the fifth day after the transplant to help prevent graft-versus-host disease (GVHD).

Also known as: FK-506, Fujimycin

Myeloablative HSCT; Reduced Intensity HSCT

Mycophenolate mofetil DRUG

Started the fifth day after the transplant to help prevent graft-versus-host disease (GVHD).

Also known as: CellCept, MMF

Myeloablative HSCT; Reduced Intensity HSCT

Eligibility Criteria

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

You may qualify if:

• Any patient with a hematological or oncological diagnosis in which allogeneic hematopoietic stem cell transplantation (HSCT) is thought to be beneficial.
• Patients without morphological or molecular evidence of disease
• For patients with "indolent diseases," if the patient has evidence of disease the disease burden must be minimal (at least PR) and the disease must be chemoresponsive. Thus for example patients with acute leukemia (not an indolent disease) must be in a morphological CR or CRp.
• For patients with RA or RARS or isolated 5q- they can proceed to transplant without any treatment.
• For patients with RAEB-1, RCMD+/-RS, or MDS NOS must have stable disease for 6 months (as documented by serial bone marrow examinations) in the absence of any therapy but growth factors or transfusion support. Patients who require treatment to "control their disease" must show chemo-responsiveness
• For patients with CMML or RAEB-2 they must demonstrate chemo-responsiveness
• Chemo-responsiveness is defined as a blast percentage decrease by at least 5 percentage points and there must be less than 10% blasts after treatment and at the time of transplant, if there are more than 10% blasts at any point during the disease course
• Chemo-responsiveness must also include at least one of the following if applicable:
• A cytogenetic response
• A well-documented decrease in transfusion requirements.
• Patients must have a related donor who is zero, one, two, three, or four antigen mismatched at the HLA-A; B; C; DR loci or an unrelated donor up to a two antigen mismatch. DNA will be retained by the tissue typing laboratory for possible typing for DQ and DP. When multiple related donor options are available donor selection will be determined the same as in the TJU two-step protocols. When multiple unrelated donors are available care will be made to avoid HLA-A and HLA-B mismatches if possible based on data from the Japanese Marrow Donor Registry studies. An HLA antibody screen will be performed on each patient.
• All patients must have adequate organ function:
• Patients with related donors must have an LVEF of \>35%. Patients with unrelated donors must have an LVEF \>45%. Patients with LVEF ≤50% and all patients with symptoms or history of heart failure or coronary artery disease must have a stress echo or equivalent test and a cardiological evaluation.
• Patients with related donors must have a DLCO \>35% of predicted corrected for hemoglobin. Patients with unrelated donors must have a DLCO \>45% of predicted corrected for hemoglobin. For related donors if the DLCO is less than 45% the EF must be greater than 45% and vice versa.
• Patients with related donors must have an adequate liver function as defined by a serum bilirubin \<3.0, AST and ALT \<3.0X upper limit of normal. Patients with unrelated donors must have an adequate liver function as defined by a serum bilirubin \<1.8, AST and ALT \< 2.5X upper limit of normal. Exceptions may be granted for patients with "benign" liver disorders such as Gilbert's disease.

You may not qualify if:

• Patients with related donors who have a combination of Performance status of \< 70% (TJU Karnofsky) and an HCT-CI of 4 points or more. Patients with unrelated donors with a combination of Performance status of \< 80% (TJU Karnofsky) and an HCT-CI of 4 points or more.
• Patients with active involvement of the central nervous system with malignancy. Patients with a disease with potential for CNS involvement should have documentation of the lack of CNS involvement via lumbar puncture or similar procedure performed within two months of admission or as per TJU standard practice guidelines.
• Patients with a psychiatric disorder that would preclude patients from complying with the protocol even with a caregiver. Patients with a lack of social support that would interfere with the ability to receive appropriate medical care will also be excluded.
• Pregnancy
• Patients with life expectancy of \< 6 months for reasons other than their underlying hematological/oncological disorder.
• Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit ant-thymocyte globulin and have an ATG level of \> 2 μg/ml. Patients on systemic corticosteroids at a dose equivalent of prednisone 7.5mg/day or higher.
• Patients who cannot receive cyclophosphamide.
• Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol.
• Patients with refractory disease.
• Patients with clinically significant preformed antibodies to their donors.
• Patients who require supplemental oxygen other than for sleep apnea will be excluded.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive 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; Graft vs Host Disease

Interventions

Whole-Body Irradiation; Radiotherapy; Cyclophosphamide; Tacrolimus; Mycophenolic Acid; fludarabine; fludarabine phosphate; Busulfan; Hematopoietic Stem Cell Transplantation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. John Wagner
• Organization: Thomas Jefferson University

JLW102@jefferson.edu

215-955-8874

Study Officials

• John L Wagner, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2011
• First Posted: May 6, 2011
• Study Start: February 10, 2011
• Primary Completion: October 31, 2022
• Study Completion: December 7, 2022
• Last Updated: December 15, 2025
• Results First Posted: December 15, 2025

Record last verified: 2025-11

Locations

US (1)