Standard-of-Care Reduced-Intensity Conditioning (RIC) With 200 Versus 400 cGy of Total Body Irradiation (TBI) in Patients With Acute Leukemia Undergoing First Allogeneic Blood or Marrow Transplantation (BMT)

NCT06803745 | Recruiting DMC

• 2 other identifiers: J24142IRB00479809
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized phase II trial of standard-of-care reduced-intensity conditioning (RIC) with 200 versus 400 cGy of total body irradiation (TBI) in patients with acute leukemia undergoing first allogeneic blood or marrow Transplantation (BMT). The primary objective is to compare the rates of graft-versus-host disease-free and relapse-free survival (GRFS) between patients in the two cohorts.

Conditions

Acute Leukemia; Acute Lymphoblastic Lymphoma

Keywords

stem cell transplant; bone marrow transplant; transplantation conditioning

Outcome Measures

Primary Outcomes (1)

• graft-versus-host disease-free, relapse-free survival (GRFS)

  Number of patients without grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, disease relapse or progression, or death by any cause from time of transplant until end of study

  2 years

Secondary Outcomes (8)

• Overall survival (OS)

  2 years

• Relapse-free survival (RFS)

  2 years

• Relapse Incidence

  2 years

• Non-relapsed mortality (NRM)

  2 years

• Graft vs Host Disease (GVHD)- moderate-to-severe chronic GVHD

  2 years

Other Outcomes (9)

• Incidence of Toxicities Grade ≥3 NCI CTCAE

  Day 0 until Day +56

• Incidence of Noninfective (Hemorrhagic Cystitis), Grade ≥2 NCI CTCAE

  Day 0 until Day +56

• Maximal Grade of Fatigue

  Day 0 until Day +56

Study Arms (2)

TBI: 200 Centigray (cGy)

ACTIVE COMPARATOR

200 cGy TBI is administered based on randomization in a single fraction on Day -3, -2, or -1, depending on if and how many days of rest are permitted. A day of rest occurring after preparative regimen completion and prior to stem cell infusion, is not routinely scheduled. Up to two days of rest may be added in this window based on logistical considerations or clinically as indicated. For one day of rest, TBI would be administered on Day -2. For two days of rest, TBI would be administered on Day -3.

Radiation: 200 cGy or 400 cGy total body irradiation (TBI)

TBI: 400 cGy

ACTIVE COMPARATOR

400 cGy TBI is administered based on randomization in a single fraction on Day -3, -2, or -1, depending on if and how many days of rest are permitted. A day of rest occurring after preparative regimen completion and prior to stem cell infusion, is not routinely scheduled. Up to two days of rest may be added in this window based on logistical considerations or clinically as indicated. For one day of rest, TBI would be administered on Day -2. For two days of rest, TBI would be administered on Day -3.

Radiation: 200 cGy or 400 cGy total body irradiation (TBI)

Interventions

200 cGy or 400 cGy total body irradiation (TBI) RADIATION

Either 200 or 400cGy will be given as part of reduced-intensity conditioning prior to consolidative allogeneic bone marrow transplant (alloBMT)

TBI: 200 Centigray (cGy); TBI: 400 cGy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 0 years
• Patients with a diagnosis of acute myeloid leukemia (AML), acute lymphoblastic leukemia or lymphoma (ALL), or acute leukemia of mixed or ambiguous lineage per the 2022 World Health Organization classifications,75,76 with \< 5% blasts on bone marrow morphologic analysis performed within 30 days of planned conditioning initiation
• AML is generally defined as ≥ 20% myeloid blasts identified in the peripheral blood and/or bone marrow. Myeloid sarcoma is also recognized as an AML-defining entity. Situations in which AML can be diagnosed without a specific blast threshold met nor myeloid sarcoma present are when fusions involving RUNX1::RUNX1T1, CBFB::MYH11, DEK:NUP214, or RBM15::MRTFA are present; rearrangements involving KMT2A, MECOM, or NUP98 exist; or there is a mutation in NPM1.
• B- or T-ALL is defined as the presence of lymphoid blasts identified in the peripheral blood and/or bone marrow with no specific blast threshold needed (acute lymphoblastic leukemia) or the presence of a lymphatic-based collection of lymphoblasts (acute lymphoblastic lymphoma).
• Acute leukemia of mixed or ambiguous lineage is defined as mixed or ambiguous lineage blasts identified in the peripheral blood and/or bone marrow or the presence of a lymphatic-based collection (lymphoma) of mixed or ambiguous lineage blasts. A specific blast threshold does not need to be met.
• i. MPN includes myelofibrosis, essential thrombocythemia, polycythemia vera, chronic neutrophilic leukemia, chronic eosinophilic leukemia, juvenile myelomonocytic leukemia, chronic myeloid leukemia (CML), or myeloproliferative neoplasm, not otherwise specified
• ii. Myelodysplastic syndrome or neoplasm (MDS)
• iii. MDS/MPN-overlap includes chronic myelomonocytic leukemia (CMML), myelodysplastic/myeloproliferative neoplasm with neutrophilia, myelodysplastic/myeloproliferative neoplasm with SF3B1 mutation and thrombocytosis, or myelodysplastic/myeloproliferative neoplasm, not otherwise specified
• No active extramedullary leukemia or known active Central Nervous System (CNS) involvement by malignancy. Such disease treated into remission is permitted.
• Patients must have a related or unrelated bone marrow or peripheral blood donor
• Human leukocyte antigen (HLA)-matched (10/10) sibling donor (MSD)
• HLA-matched (10/10) unrelated donor (MUD)
• HLA-haploidentical (5/10) related donor (Haplo)
• HLA-mismatched (6-9/10) unrelated donor (mMUD)
• Planned allogeneic BMT using post-transplantation cyclophosphamide (PTCy) as a component of GVHD prophylaxis

You may not qualify if:

• Acute leukemia with promyelocytic leukemia (PML)/retinoic acid receptor α (RARA) fusion
• Prior allogeneic BMT
• Eastern Cooperative Oncology Group (ECOG) Performance Status \> 2 or Karnofsky/Lansky score \< 60
• Patients with an additional active malignancy with a life expectancy \< 2 years due to that disease
• Symptomatic coronary artery disease
• Uncontrolled infection
• Patients who are pregnant or breastfeeding

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

RECRUITING

Study Officials

• Jonathan Webster

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jonathan Webster, MD

CONTACT

410-614-9106; jwebst17@jhmi.edu

Preston Clairborne, MD

CONTACT

4109558893; jclaibo8@jh.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2025
• First Posted: January 31, 2025
• Study Start: March 27, 2025
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): September 30, 2030
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)