Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation

NCT03734601 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB-47407BMT330
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate whether addition of a low dose of total body irradiation (TBI) to a standard preparation for transplant \[total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG)\] conditioning will help to augment donor chimerism without reducing tolerability of this regimen or increasing the risk of graft-vs-host disease (GVHD)

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes; Myeloproliferative Disorder; Chronic Lymphocytic Leukemia; B-cell Lymphoma; T-cell Lymphoma; Non Hodgkin Lymphoma; Hodgkin Lymphoma; Chronic Myelomonocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Full-dose Donor Chimerism (FDC) at Day 28 Following TLI/ATG/TBI Conditioning.

  Subsequent to TLI/ATG/TBI conditioning, the proportion of participants with full dose donor chimerism (FDC) will be determined by Day 28. FDC is defined as achieving ≥ 95% donor type in the CD3+ lineage within 28 days of donor cell infusion, as assessed by short tandem repeat (STR) testing. The outcome will be expressed as the number of participants that achieve FDC by Day 28, a number without dispersion.

  Day 28

Secondary Outcomes (5)

• Disease Progression

  1 year

• Overall Survival (OS)

  1 year

• Event-free Survival (EFS) at 1 Year

  1 year

• Non-relapse Mortality (NRM)

  1 year

• Graft vs Host Disease (GvHD)

  1 year

Study Arms (1)

TBI+TLI

EXPERIMENTAL

TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen)

Radiation: Total body irradiation (TBI); Drug: Anti-thymocyte globulin (ATG); Drug: Tacrolimus; Drug: Mycophenolate mofetil (MMF); Radiation: Total lymphoid irradiation (TLI)

Interventions

Total body irradiation (TBI) RADIATION

Administer Total body irradiation (TBI) 80 cGy on Day 1 of standard TLI ATG conditioning

TBI+TLI

Anti-thymocyte globulin (ATG) DRUG

Given intravenous (IV), Dose 1.5 mg/kg x 5 days

TBI+TLI

Tacrolimus DRUG

Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV)

Also known as: Fujimycin

TBI+TLI

Mycophenolate mofetil (MMF) DRUG

Given Oral, 15 mg/k every 2 hours for peripheral blood stem cells (PBSC) from matched related donors; 15 mg/kg every 8 hours for PBSC from unrelated donors (URDs) or mismatched related donors.

Also known as: Cellcept, MMF

TBI+TLI

Total lymphoid irradiation (TLI) RADIATION

9 x 120 cGy over 11 days

TBI+TLI

Eligibility Criteria

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

You may qualify if:

• Has a human leukocyte antigen (HLA)-matched or single allele mismatched adult sibling donor or unrelated donor.
• Acute myeloid leukemia (AML); myelodysplastic syndrome (MDS); myeloproliferative disease syndrome (MPD)\]; chronic lymphocytic leukemia (CLL); B- or T-cell non Hodgkin lymphoma (NHL); Hodgkin lymphoma (HL); or chronic myelomonocytic leukemia (CMML), suitable for treatment with allogeneic transplant after TLI and ATG reduced intensity conditioning.
• Considered at high-risk for regimen-related toxicity from fully-ablative transplant conditioning (therefore reduced-intensity conditioning is recommended).
• Ability to understand and the willingness to sign a written informed consent document. Patients must have signed informed consent to participate in the trial.

You may not qualify if:

• Uncontrolled bacterial, viral or fungal infection defined as currently taking medication and progression of clinical symptoms.
• Progressive hemato lymphoid malignancy despite conventional therapy.
• Chronic myelogenous leukemia (CML).
• Active CNS involvement of the underlying malignancy.
• HIV positive
• Pregnant or lactating
• Prior malignancy (EXCEPTION: diagnosed \> 5 years ago without evidence of disease, OR treated ≤ 5 years ago but have a greater than 50% chance of life expectancy of ≥ 5 years for that malignancy).
• Have a psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of the primary physician would place the patient at an unacceptable risk from transplant.
• Left ventricular ejection fraction (LEVF) \< 30%, or uncontrolled cardiac failure
• Diffusing capacity of lung for carbon monoxide (DLCO) \< 40% predicted
• Total bilirubin \> 3 mg/dL
• Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase (SGPT) \> 4 x upper limit of normal (ULN)
• Creatinine \> 2 mg/dL and an estimated creatinine clearance \< 40 mL/min
• Poorly-controlled hypertension despite multiple antihypertensive medications
• Karnofsky Performance Status (KPS) \< 60%

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Myeloproliferative Disorders; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Hodgkin Disease; Leukemia, Myelomonocytic, Chronic

Interventions

Whole-Body Irradiation; Antilymphocyte Serum; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Myelodysplastic-Myeloproliferative Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Robert Lowsky, Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)
• Organization: Stanford University

rlowsky@stanford.edu

650-723-0822

Study Officials

• Robert Lowsky, MD

  Stanford 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: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Study Record Dates

• First Submitted: November 6, 2018
• First Posted: November 8, 2018
• Study Start: November 5, 2018
• Primary Completion: December 26, 2019
• Study Completion: November 17, 2020
• Last Updated: December 12, 2023
• Results First Posted: June 11, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)