Total Marrow and Lymphoid Irradiation as Conditioning Regimen Before Hematopoietic Cell Transplantation in Patients With Myelodysplastic Syndrome or Acute Leukemia

NCT04262843 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 19518NCI-2019-08984
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well total marrow and lymphoid irradiation works as a conditioning regimen before hematopoietic cell transplantation in patients with myelodysplastic syndrome or acute leukemia. Total body irradiation can lower the relapse rate but has some fatal side effects such as irreversible damage to normal internal organs and graft-versus-host disease (a complication after transplantation in which donor's immune cells recognize the host as foreign and attack the recipient's tissues). Total body irradiation is a form of radiotherapy that involves irradiating the patient's entire body in an attempt to suppress the immune system, prevent rejection of the transplanted bone marrow and/or stem cells and to wipe out any remaining cancer cells. Intensity-modulated radiation therapy (IMRT) is a more recently developed method of delivering radiation. Total marrow and lymphoid irradiation is a method of using IMRT to direct radiation to the bone marrow. Total marrow and lymphoid irradiation may allow a greater dose of radiation to be delivered to the bone marrow as a preparative regimen before hematopoietic cell transplant while causing less side effects to normal organs than standard total body irradiation.

Conditions

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; High Risk Myelodysplastic Syndrome; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Evaluated using the Bearman scale and National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Up to day 100

• Graft-versus-host disease (GvHD) free relapse-free survival

  Time from start of protocol therapy to grade 3-4 acute GvHD, chronic GvHD requiring systemic treatment, death, relapse/progression, or last follow-up, whichever comes first, assessed up to 2 years post-transplant

Secondary Outcomes (11)

• Overall survival

  Time from start of protocol therapy to death from any cause, or last follow-up, whichever comes first, assessed up to 2 years post-transplant

• Relapse-free survival

  Time from the start of protocol therapy to the date of death, disease relapse, or last follow-up, whichever comes first, assessed up to 2 years post-transplant.]

• Time to relapse/progression

  Time from the start of protocol therapy to death, disease relapse or progression, or last follow-up, whichever comes first, assessed up to 2 years post-transplant

• Non-relapse mortality

  Time from start of therapy until non-disease related death, or last follow-up, whichever comes first, assessed up to 2 years post-transplant

• Incidence of adverse events that meet grade 3, 4, or 5 per CTCAE version 5.0

  From day -9 to day -1, from day 0 to day 30, and day 31 to day 100 post-transplant

Other Outcomes (5)

• Minimal residual disease

  At day 30, 100, and 180 days, and 1 year post-transplant

• Immune cell recovery

  Up to 2 years

• GvHD biomarker analysis

  Up to 2 years

Study Arms (1)

Treatment (fludarabine, TMLI, HCT, cyclophosphamide)

EXPERIMENTAL

CONDITIONING: Patients receive fludarabine IV QD on days -7 to -5, and undergo TMLI BID on days -4 to 0 in the absence of disease progression or unacceptable toxicity. TRANSPLANT: Patients undergo hematopoietic cell transplantation on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV QD on days 3-4 in the absence of disease progression or unacceptable toxicity. Beginning on day 5, patients also receive granulocyte colony stimulating factor and tacrolimus/mycophenolate mofetil per institutional standard.

Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Fludarabine Phosphate; Biological: Granulocyte Colony-Stimulating Factor; Procedure: Hematopoietic Cell Transplantation; Procedure: Intensity-Modulated Radiation Therapy; Drug: Mycophenolate Mofetil; Drug: Tacrolimus

Interventions

Granulocyte Colony-Stimulating Factor BIOLOGICAL

Growth factor therapy

Also known as: Colony Stimulating Factor 3, Colony-Stimulating Factor (Granulocyte), Colony-Stimulating Factor 3, CSF3, G CSF, G-CSF, Granulocyte Colony Stimulating Factor, Pluripoietin

Treatment (fludarabine, TMLI, HCT, cyclophosphamide)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, 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, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (fludarabine, TMLI, HCT, cyclophosphamide)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (fludarabine, TMLI, HCT, cyclophosphamide)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (fludarabine, TMLI, HCT, cyclophosphamide)

Hematopoietic Cell Transplantation PROCEDURE

Undergo hematopoietic cell transplantation

Also known as: HCT, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell Transplant, stem cell transplantation

Treatment (fludarabine, TMLI, HCT, cyclophosphamide)

Intensity-Modulated Radiation Therapy PROCEDURE

Undergo TMLI

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

Treatment (fludarabine, TMLI, HCT, cyclophosphamide)

Mycophenolate Mofetil DRUG

Immunosuppressive therapy

Also known as: Cellcept, MMF

Treatment (fludarabine, TMLI, HCT, cyclophosphamide)

Tacrolimus DRUG

Immunosuppressive therapy

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (fludarabine, TMLI, HCT, cyclophosphamide)

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Karnofsky performance status \>= 70
• Histologically confirmed diagnosis of one the following:
• Patients with acute myelogenous leukemia
• In first complete remission (CR1) with intermediate or poor risk cytogenetics according to National Comprehensive Cancer Network (NCCN) guidelines for acute myeloid leukemia (AML) or European LeukemiaNet (ELN) 2017
• In second complete remission (CR2) or third complete remission (CR3)
• Patients with chemosensitive active disease
• Patients with acute lymphocytic leukemia
• In CR1 with poor risk cytogenetics:
• For adults according to NCCN guidelines for acute lymphoblastic leukemia (ALL): Patients older than 40 year of age; with high white blood cell count (WBC) at diagnosis (\>= 30,000 for B lineage or \>= 50,000 for T lineage), or with high risk cytogenetics including: hypoploidy (\< 44 chromosomes); t(v;11q23): MLL rearranged; t(9;22) (q34;q11.2); complex cytogenetics (5 or more chromosomal abnormalities)
• For pediatrics t(9;22), iAMP21loss of 13q, and abnormal 17p
• In CR2 or CR3
• Patients with chemosensitive active disease
• Myelodysplastic syndrome in high-intermediate (int-2) and high risk categories by International Prognostic Scoring System (IPSS) or revised (R)-IPSS
• Total bilirubin =\< 2 X upper limit of normal (ULN) (unless has Gilbert's disease) (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)

You may not qualify if:

• Patients should not have any uncontrolled illness including ongoing or active bacterial, viral or fungal infection
• Patient may not be receiving any other investigational agents or concurrent biological, intensive chemotherapy or radiation therapy for the previous three weeks from conditioning
• (NOTE: Low dose chemotherapy or maintenance chemotherapy given within 7 days of planned study enrollment is permitted. These include: Hydroxyurea, 6-meraptopurine, oral methotrexate, vincristine, oral etoposide, and tyrosine kinase inhibitors \[TKIs\]. FLT-3 inhibitors such as sorafenib, crenolanib, midostaurin can also be given up to 3 days before conditioning regimen.)
• Herbal medications dependency
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• No intercurrent illness or other malignancy (other than non-melanoma skin cancer)
• Active infection requiring antibiotics
• Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
• Females only: Pregnant or breastfeeding
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Patients who had a prior autologous or allogeneic transplant
• Patients who had prior radiation therapy of more than 20% of bone marrow containing areas or to any area exceeding 2000 cGy
• Patients with HLA-matched or partially matched (7/8 or 8/8) related or fully matched unrelated donor available to donate
• Patients who have received more than 3 prior regimens, where the regimen intent was to induce remission
• Patients with treatment history including anti-CD33 monoclonal antibody therapy (e.g., SGN-CD33 or Mylotarg)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Granulocyte Colony-Stimulating Factor; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Radiotherapy, Intensity-Modulated; Mycophenolic Acid; Tacrolimus

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones

Study Officials

• Monzr M Al Malki

  City of Hope Medical Center

  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: February 3, 2020
• First Posted: February 10, 2020
• Study Start: February 7, 2020
• Primary Completion (Estimated): June 23, 2026
• Study Completion (Estimated): June 23, 2026
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

US (1)