2-Step Approach to Stem Cell Transplant in Treating Participants With Hematological Malignancies

A 2 Step Approach to Matched Related Hematopoietic Stem Cell Transplantation for Patients With Hematological Malignancies-5+5 Dosing

This phase II trial studies how well a 2-step approach to stem cell transplant works in treating patients with blood cancers. Giving chemotherapy and total body irradiation before a lymphocyte (white blood cell) and stem cell transplant helps stop the growth of cells in the bone marrow including normal blood-forming cells (stem cells) and cancer cells. By giving the donor cells in two steps, the dose of lymphocytes given can be tightly controlled and they can be made more tolerant to the body. When the healthy lymphocytes and 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 called graft versus host disease. Giving tacrolimus and mycophenolate mofetil may stop this from happening.

Study Overview

• Status: Completed
• Conditions: Hematopoietic and Lymphoid Cell Neoplasm
• Intervention / Treatment: Drug: Cyclophosphamide; Radiation: Total-Body Irradiation; Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Donor Lymphocyte Infusion

Detailed Description

PRIMARY OBJECTIVES:

I. To assess whether providing a patient with "5+5" dosing in a 2 step matched related donor hematopoietic stem cell transplantation (HSCT) increases the percentage of patients who achieve full donor chimerism earlier as defined by 98% or greater donor T cell chimerism at 28 days post HSCT (d+28).

SECONDARY OBJECTIVES:

I. To assess day (d) +90 chimerism in patients receiving "5+5" dosing. II. To assess post HSCT relapse rates in patients receiving "5+5" dosing. III. To assess rates of grade II-IV graft versus host disease (GVHD) in patients receiving "5+5" dosing.

IV. To assess treatment-related mortality (TRM) in patients receiving "5+5" dosing.

EXPLORATORY OBJECTIVES:

I. To assess whether patients receiving "5+5" dosing have lower rates of cytomegalovirus (CMV) reactivation as compared to patients treated on Thomas Jefferson University (TJU) 08D.85 (1st Generation 2-Step Matched Related Trial).

OUTLINE:

CONDITIONING REGIMEN: Patients undergo total body irradiation (TBI) twice daily (BID) on days -9 to -6.

TRANSPLANT: Patients receive donor lymphocytes intravenously (IV) on day -6 after the last dose of TBI.

CONDITIONING REGIMEN: Patients receive cyclophosphamide IV on days -3 and -2.

TRANSPLANT: Patients undergo hematopoietic stem cell transplantation on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42 in the absence of GVHD, a suspicion of GVHD, or previous history of GVHD requiring a taper delay. Patients also receive mycophenolate mofetil IV BID beginning on day -1 through day 28 in the absence of GVHD.

After completion of study treatment, patients are followed up at days 28, 90, 180, 270, and 365.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Sidney Kimmel Cancer Center at 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:

• Provide signed and dated informed consent form.
• Have a hematological malignancy or any type of dyscrasia in which allogeneic HSCT is thought to be beneficial.
• Have a related donor who is no more than a 1-antigen mismatch at the human leukocyte antigen (HLA)-A; B; C; DR loci in the GVHD direction with the patient. (Patients with a syngeneic donor may be treated on this therapeutic approach, but their outcomes will not be part of the statistical aims of the study.
• LVEF (left ventricular end diastolic function) of >= 45%.
• DLCO (diffusing capacity of the lung for carbon monoxide) >= 50% of predicted corrected for hemoglobin.
• FEV-1 (forced expiratory volume at 1 second >= 50% of predicted.
• Serum bilirubin =< 1.8.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x upper limit of normal.
• Creatinine clearance of >= 60 mL/min.
• Have a Hematopoietic Cell Transplant Comorbidity Index (HCT-CI) score =< 5 points (patients with greater than 5 points will be allowed for trial with approval of the principal investigator [PI] and at least 1 co-investigator [co-I] not on the primary care team of the patient). This is an adjustment to account for healthy patients who meet the spirit of this protocol but have histories that result in higher than HCT-CI 5 points. An example is a patient with a solid tumor malignancy in their remote history (adds 3 points to HCT-CI total) where the treatment for the malignancy occurred years to decades before and there has been complete recovery of toxicities.
• Have a Karnofsky performance score (KPS) >= 80%.
• Women of reproductive potential (defined as women under the age of 50 years still menstruating within 2 months of HSCT despite past history of chemotherapy) will be counseled to use highly effective contraception including oral, intramuscular (IM), or patch contraceptives, intrauterine device (IUD), diaphragm, cervical cap, or contraceptive implant. Pharmacological avoidance of pregnancy and suppression of menstruation may be instituted during the HSCT inpatient stay.
• Men will be asked to abstain from sexual relations during the treatment period of the HSCT stay.
• DONOR: All donors are selected and screened for their ability to provide adequate infection-free apheresis products for the patient in a manner that does not put the donor at risk for negative consequences.

Exclusion Criteria:

• Be human immunodeficiency virus (HIV) positive.
• Be pregnant or breastfeeding.
• Have received alemtuzumab or rabbit antithymocyte globulin (ATG) within 8 weeks or horse ATG within 6 weeks of the transplant admission. This exclusion criterion will be documented by the absence of these drugs in the medical record.
• Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol without the specific approval of the PI. If the PI disregards this criterion (example of this is localized prostate cancer not yet requiring treatment), the rationale must be documented in the study binder). This exclusion criterion will be documented by the absence of these drugs in the medical record.

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: Treatment (TBI, DLI, chemotherapy, HSCT, tacrolimus, MMF); Description CONDITIONING REGIMEN: Participants undergo TBI BID on days -9 to -6. TRANSPLANT: Participants receive donor lymphocytes IV on day -6 after the last dose of TBI. CONDITIONING REGIMEN: Participants receive cyclophosphamide IV on days -3 and -2. TRANSPLANT: Participants undergo hematopoietic stem cell transplantation on day 0. GVHD PROPHYLAXIS: Participants receive tacrolimus IV beginning on day -1 with taper beginning on day 42 in the absence of GVHD, a suspicion of GVHD, or previous history of GVHD requiring a taper delay. Participants also receive mycophenolate mofetil IV BID beginning on day -1 through day 28 in the absence of GVHD.

Drug: Cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; (-)-Cyclophosphamide; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate; 1-bis(2-chloroethyl)-amino-1-oxo-2-aza-5-oxaphosphoridin monohydrate; 2-[bis(b-chloroethyl)amino]-1-oxa-3-aza-2-phosphacyclohexane-2-oxide monohydrate; 2-[di(chloroethyl)amino]-1-oxa-3-aza-2-phosphacyclohexane 2-oxide monohydrate; 2H-1,3,2-Oxazaphosphorine; 6055-19-2; bis(2-chloroethyl)phosphamide cyclic propanolamide ester monohydrate; Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester monohydrate; N,N-bis(2-chloroethyl)-N',O-propylenephosphoric acid ester diamide monohydrate; N,N-bis(2-chloroethyl)-N'-(3-hydroxypropyl)phosphorodiamidic acid intramolecular ester monohydrate; N,N-bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide monohydrate; N,N-bis(b-chloroethyl)-N',O-trimethylenephosphoric acid ester diamide monohydrate; N,N-bis(beta-chloroethyl)-N',O-propylenephosphoric acid ester diamide monohydrate; N,N-bis(beta-chloroethyl)-N',O-trimethylenephosphoric acid ester diamide monohydrate; 2-[bis(2-chloroethyl)amino]tetrahydro; 2-oxide, monohydrate; Radiation: Total-Body Irradiation; Undergo TBI; Other Names: TBI; SCT_TBI; Whole Body Irradiation; Whole-Body Irradiation; Whole Body; TOTAL BODY IRRADIATION; Drug: Mycophenolate Mofetil; Given IV; Other Names: Cellcept; MMF; 115007-34-6; 128794-94-5; Drug: Tacrolimus; Given IV; Other Names: Prograf; Hecoria; FK 506; Fujimycin; Protopic; 109581-93-3; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Undergo HSCT; Other Names: Allogeneic; Allogeneic Hematopoietic Cell Transplantation; HSC; HSCT; allogeneic stem cell transplantation; Stem Cell Transplantation; Procedure: Donor Lymphocyte Infusion; Given IV; Other Names: DLI; Donor Leukocyte Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Donor T cell chimerism	For chimerism rates, the method of Atkinson and Brown will be used to allow for the two-stage design. Will be presented with corresponding 95% confidence intervals.	At day +28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Donor T cell chimerism	Will be presented with corresponding 95% confidence intervals. For chimerism rates, the method of Atkinson and Brown will be used to allow for the two-stage design.	At day +90
Relapse rate	Will be presented with corresponding 95% confidence intervals.	At 1 year post-hematopoietic stem cell transplantation (HSCT)
Incidence of grades II-IV graft versus host disease (GVHD)	Will be presented with corresponding 95% confidence intervals.	Within 1 year of HSCT
Rate of treatment-related mortality (TRM)	Will be presented with corresponding 95% confidence intervals.	At 1 year post-HSCT

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of cytomegalovirus	Rate of cytomegalovirus	Up to 100 days

Collaborators and Investigators

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Investigators: Principal Investigator: USAMA GERGIS, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University

Publications and helpful links

Helpful Links

• Thomas Jefferson University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2018
• Primary Completion (Actual): March 19, 2025
• Study Completion (Actual): March 19, 2025

Study Registration Dates

• First Submitted: October 17, 2018
• First Submitted That Met QC Criteria: October 17, 2018
• First Posted (Actual): October 19, 2018

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 20, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Hematologic Neoplasms; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antibiotics, Antitubercular; Antitubercular Agents; Calcineurin Inhibitors; Cyclophosphamide; Mycophenolic Acid; Tacrolimus
• Other Study ID Numbers: 18D.419; JT 12822 (Other Identifier: JeffTrial Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes