Total Marrow and Lymphoid Irradiation Before Donor Transplant and Cyclophosphamide in Treating Patients With Acute Myeloid Leukemia

NCT03467386 | Suspended Phase 1 DMC FDA Drug FDA Device

• 2 other identifiers: 17423NCI-2018-00177
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase I trial studies the side effects of total bone marrow and lymphoid irradiation and how well it works with cyclophosphamide in treating patients with acute myeloid leukemia. Total marrow and lymphoid irradiation targets cancer in bone marrow and blood, instead of applying radiation to the whole body. Giving total bone marrow and lymphoid irradiation before a donor transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving total bone marrow and lymphoid irradiation before donor transplant and cyclophosphamide after transplant may work better at treating acute myeloid leukemia.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• 1a. Incidence of adverse events

  Assessed using Bearman Scale Regimen-Related Toxicity scale. Scale range: Grade 0-4 (increasing grade reflects increasing severity), where Grade 0-none/did not experience and Grade 4=death.

  Up to 24 months

• 1b. Incidence of adverse events

  Assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 scale. Scale range: Grade 1-5 (increasing grade reflects increasing severity), where Grade 1 reflects a more milder form of the adverse event and Grade 5=death.

  Up to 24 months

Secondary Outcomes (18)

• Time to neutrophil and platelet recovery/engraftment

  From day 0 to recovery or declaration of engraftment failure, assessed up to 24 months

• Acute graft versus host disease (GvHD)

  Day 0 to 100 (120) days post-transplant

• Chronic GVHD

  From day (80) 100 to the onset of chronic GvHD, death or last contact, whichever comes first, assessed up to 24 months

• GvHD-free/relapse-free survival (GRFS)

  From start of treatment (hematopoietic stem cell transplant [HCT]) to grade 3-4 acute GvHD, chronic GvHD requiring systemic treatment, relapse, or death (from any cause), whichever occurs first, assessed p to 24 months

• Levels of immune cells

  Up to 24 months

Study Arms (1)

Treatment (TMLI, cyclophosphamide)

EXPERIMENTAL

Patients undergo TMLI BID on days -4 to 0, then undergo bone marrow or peripheral blood stem cell transplant on day 0. Patients receive cyclophosphamide IV over 2 hours on days 3 and 4, tacrolimus given by CIV on days 5-90, and filgrastim beginning on day 5 until ANC is at least 1,500/mm\^3 for 3 consecutive days.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Biological: Filgrastim; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Tacrolimus; Radiation: Total Marrow Irradiation

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo alloHCT

Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Treatment (TMLI, 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 (TMLI, cyclophosphamide)

Filgrastim BIOLOGICAL

Administer according to City of Hope standard operating procedures

Also known as: G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim

Treatment (TMLI, cyclophosphamide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (TMLI, cyclophosphamide)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (TMLI, cyclophosphamide)

Questionnaire Administration OTHER

Ancillary studies

Treatment (TMLI, cyclophosphamide)

Tacrolimus DRUG

Given CIV

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

Treatment (TMLI, cyclophosphamide)

Total Marrow Irradiation RADIATION

Undergo TMLI

Treatment (TMLI, cyclophosphamide)

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• This study is open to patients with acute myeloid leukemia (AML) evaluated within 30 days of the start of conditioning regimen and in first or second complete remission (CR)
• Karnofsky performance status (KPS) \>= 70%
• The effects of radiation on the developing fetus are known to be teratogenic; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
• Patients with acute myelogenous leukemia (AML) who are in first or second complete remission
• All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR) identical sibling who is willing to donate primed blood stem cells (preferred) or bone marrow, or have a 10/10 allele matched unrelated donor; all ABO blood group combinations of the donor/recipient are acceptable since even major ABO compatibilities can be dealt with by various techniques; (red cell exchange or plasma exchange)
• A cardiac evaluation with an electrocardiogram showing no ischemic changes or abnormal rhythm and an ejection fraction of \>= 50% established by multi-gated acquisition scan (MUGA) or echocardiogram
• Patients must have a serum creatinine of less than or equal to 1.3 mg/dL or creatinine clearance \> 70 ml/min as calculated by the Cockcroft-Gault formula
• A bilirubin of less than or equal to 1.5 mg/dL, excluding patients with Gilbert's disease
• Patients should also have a serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) less than 5 times the upper limit of normal
• Pulmonary function tests including diffusing capacity of the lung for carbon monoxide (DLCO) will be performed; forced expiratory volume in 1 second (FEV 1) and DLCO should be greater than 50% of predicted normal value
• All subjects must have the ability to understand and the willingness to sign a written informed consent; signed informed consent form approved by the Institutional Review Board (IRB) is required; the patient, family member, and transplant staff physician (physician, nurse, and social worker) meet at least once prior to starting the transplant procedure; during this meeting, all pertinent information with respect to risks and benefits to the donor and recipient will be presented; alternative treatment modalities will be discussed
• The time from the end of last induction, re-induction, or consolidation regimen should be greater than or equal to 14 days
• Prior therapy with etoposide and cyclophosphamide is allowed
• DONOR: donor evaluation and eligibility will be assessed as per current City of Hope standard operating procedure (SOP)

You may not qualify if:

• Patients should not have any uncontrolled illness including ongoing or active or poorly controlled infection
• Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy; maintenance therapy with Food and Drug Administration (FDA)-approved targeted therapies (e.g. tyrosine kinase inhibitors for Philadelphia chromosome \[Ph\] positive \[+\] acute lymphoblastic leukemia \[ALL\], and FLT inhibitors for FLT3+ patients) will be allowed after day 60 disease assessment
• Prior radiation therapy that would exclude the use of TMLI
• Relapsed patients who have undergone autologous or allogeneic hematopoietic stem cell transplantation previously
• Patients with psychological or medical condition that patient's physician deems unacceptable to proceed to allogeneic hematopoietic stem cell transplantation
• Electrocardiogram (EKG) showing ischemic changes or abnormal rhythm and/or an echocardiogram or MUGA scan showing abnormal wall motion or ejection fraction \< 50%
• Patients who have been treated with chemotherapy or radiation for the purpose of induction, re-induction or consolidation, within two weeks of planned study enrollment
• Patients with other active malignancies are ineligible for this study, other than localized malignancies
• Patients that are 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 or compliance with clinical study procedures, including but not limited to, infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.
• Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

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

Leukemia, Myeloid, Acute

Interventions

Stem Cell Transplantation; Cyclophosphamide; Filgrastim; Granulocyte Colony-Stimulating Factor; Tacrolimus

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; 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; Macrolides; Lactones

Study Officials

• Anthony S Stein

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2018
• First Posted: March 16, 2018
• Study Start: March 19, 2018
• Primary Completion (Estimated): September 6, 2026
• Study Completion (Estimated): September 6, 2026
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (1)