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

NCT03712878 | Completed Phase 2 DMC FDA Device

• 2 other identifiers: 18D.419JT 12822
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hematopoietic and Lymphoid Cell Neoplasm

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Donor T cell chimerism

  At day +90

• Relapse rate

  At 1 year post-hematopoietic stem cell transplantation (HSCT)

• Incidence of grades II-IV graft versus host disease (GVHD)

  Within 1 year of HSCT

• Rate of treatment-related mortality (TRM)

  At 1 year post-HSCT

Other Outcomes (1)

• Rate of cytomegalovirus

  Up to 100 days

Study Arms (1)

Treatment (TBI, DLI, chemotherapy, HSCT, tacrolimus, MMF)

EXPERIMENTAL

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.

Radiation: Total-Body Irradiation; Procedure: Donor Lymphocyte Infusion; Drug: Cyclophosphamide; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Tacrolimus; Drug: Mycophenolate Mofetil

Interventions

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: SCT_TBI, TBI, TOTAL BODY IRRADIATION, Whole Body, Whole Body Irradiation, Whole-Body Irradiation

Treatment (TBI, DLI, chemotherapy, HSCT, tacrolimus, MMF)

Donor Lymphocyte Infusion PROCEDURE

Given IV

Also known as: DLI, Donor Leukocyte Infusion

Treatment (TBI, DLI, chemotherapy, HSCT, tacrolimus, MMF)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 1-bis(2-chloroethyl)-amino-1-oxo-2-aza-5-oxaphosphoridin monohydrate, 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide 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, 2-[bis(2-chloroethyl)amino]tetrahydro, 2-oxide, monohydrate, 6055-19-2, bis(2-chloroethyl)phosphamide cyclic propanolamide ester monohydrate, Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, 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, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (TBI, DLI, chemotherapy, HSCT, tacrolimus, MMF)

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo HSCT

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, allogeneic stem cell transplantation, HSC, HSCT, Stem Cell Transplantation

Treatment (TBI, DLI, chemotherapy, HSCT, tacrolimus, MMF)

Tacrolimus DRUG

Given IV

Also known as: 109581-93-3, FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (TBI, DLI, chemotherapy, HSCT, tacrolimus, MMF)

Mycophenolate Mofetil DRUG

Given IV

Also known as: 115007-34-6, 128794-94-5, Cellcept, MMF

Treatment (TBI, DLI, chemotherapy, HSCT, tacrolimus, MMF)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• Be human immunodeficiency virus (HIV) positive.
• Be pregnant or breastfeeding.

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Thomas Jefferson University Hospital

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Whole-Body Irradiation; Cyclophosphamide; Stem Cell Transplantation; Tacrolimus; 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; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• USAMA GERGIS, MD

  Sidney Kimmel Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

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: October 17, 2018
• First Posted: October 19, 2018
• Study Start: September 19, 2018
• Primary Completion: March 19, 2025
• Study Completion: March 19, 2025
• Last Updated: August 22, 2025

Record last verified: 2025-08

Locations

US (1)