Organ-Sparing Marrow-Targeted Irradiation Before Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

NCT02122081 | Completed Phase 1 DMC FDA Device

• 2 other identifiers: OSU-13219NCI-2014-00763
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot clinical trial aims to assess feasibility and tolerability of using an LINAC based "organ-sparing marrow-targeted irradiation" to condition patients with high-risk hematological malignancies who are otherwise ineligible to undergo myeloablative Total body irradiation (TBI)-based conditioning prior to allogeneic stem cell transplant. The target patient populations are those with ALL, AML, MDS who are either elderly (\>50 years of age) but healthy, or younger patients with worse medical comorbidities (HCT-Specific Comorbidity Index Score (HCT-CI) \> 4). The goal is to have the patients benefit from potentially more efficacious myeloablative radiation based conditioning approach without the side effects associated with TBI.

Conditions

Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• TRM, defined as death occurring in a patient from causes other than disease relapse

  Proportions will be derived for incidence of TRM divided by all evaluable patients along with corresponding 95% binomial confidence intervals.

  At day 30 post-transplant

• Rate of grade II/III organ toxicity, defined by the Bearman Regimen-Related Toxicities Scale

  Toxicities will be tabulated by grade for each cohort, by type of toxicity, as well as the maximum grade overall. Toxicity frequencies will be described for the day +30, day +100, and one year time intervals as well as cumulative over time. Proportions will be derived for incidence of grade II/III organ toxicity divided by all evaluable patients along with corresponding 95% binomial confidence intervals.

  Up to 30 days

Secondary Outcomes (12)

• TRM

  Day 100 post-transplant

• Donor chimerism

  Day 100

• Incidence of aGVHD, graded according to Ohio State University Bone Marrow Transplant (OSU BMT) Program policy

  Up to day 100

• Incidence of chronic GVHD, scored according to the OSU BMT Program policy

  At 1 year

• Cumulative incidence of grade II organ toxicity

  Up to day 100

Study Arms (1)

Treatment (OSMI, allogeneic transplant)

EXPERIMENTAL

CONDITIONING REGIMEN: Patients undergo organ-sparing marrow irradiation BID on days -6 to -4 and receive cyclophosphamide IV over 1-2 hours every 24 hours on days -3 to -2. Patients with an unrelated donor also receive anti-thymocyte globulin every 24 hours on days -4 to -2. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 and continuing for at least 6 months and methotrexate IV on days 1, 3, 6, and 11. TRANSPLANT: Patients undergo allogeneic peripheral blood progenitor cell or bone marrow transplant on day 0.

Radiation: radiation therapy; Drug: cyclophosphamide; Biological: anti-thymocyte globulin; Drug: tacrolimus; Drug: methotrexate; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Other: laboratory biomarker analysis

Interventions

radiation therapy RADIATION

Undergo organ-sparing marrow irradiation BID on days -6 to -4

Also known as: irradiation, radiotherapy, therapy, radiation

Treatment (OSMI, allogeneic transplant)

cyclophosphamide DRUG

Given IV over 1-2 hours every 24 hours on days -3 to -2.

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Treatment (OSMI, allogeneic transplant)

anti-thymocyte globulin BIOLOGICAL

Also known as: ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin

Treatment (OSMI, allogeneic transplant)

tacrolimus DRUG

Given IV or PO

Also known as: FK 506, Prograf

Treatment (OSMI, allogeneic transplant)

methotrexate DRUG

Given IV

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX

Treatment (OSMI, allogeneic transplant)

allogeneic bone marrow transplantation PROCEDURE

Undergo allogeneic peripheral blood progenitor cell or bone marrow transplant on day 0

Also known as: bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow

Treatment (OSMI, allogeneic transplant)

allogeneic hematopoietic stem cell transplantation PROCEDURE

Undergo allogeneic peripheral blood progenitor cell or bone marrow transplant

Treatment (OSMI, allogeneic transplant)

peripheral blood stem cell transplantation PROCEDURE

Undergo allogeneic peripheral blood progenitor cell or bone marrow transplant

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Treatment (OSMI, allogeneic transplant)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (OSMI, allogeneic transplant)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a diagnosis of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndromes (MDS) with fewer than 10% myeloblasts or lymphoblasts in the bone marrow and no blasts in the peripheral blood on morphologic analysis performed within 30 days of start of the conditioning regimen; if remission bone marrow is available beyond 30 days a new bone marrow evaluation is required to assess remission status
• The diagnosis of AML, ALL, or MDS will be based on World Health Organization (WHO) criteria
• Pre-transplant bone marrow sample must be evaluable for assessment of remission status (i.e. aspirate smear containing particles and/or evaluable bone marrow core biopsy)
• Patients with leukemia infiltration in the central nervous system (CNS) are eligible if cerebrospinal fluid (CSF) cytospin is negative for myeloblasts or lymphoblasts at time of enrollment
• If the patient has an intra-abdominal chloroma on presentation, and has a partial response or complete response to treatment (size reduction of chloroma and marrow blast \< 10%), the patient is eligible; however the chloroma must be included as part of the treatment target
• For patients receiving treatment of their AML, MDS or ALL prior to transplantation:
• Interval between the start of a cycle of conventional cytotoxic chemotherapy and the start of conditioning regimen must be at least 30 days
• Interval between completing treatment with a hypomethylating agent or other non-cytotoxic chemotherapy and the start of conditioning regimen must be at least 10 days
• Hematopoietic Cell Transplantation-Specific Comorbidity Index score (HCT-CI) =\< 4 for patients in Cohort 1 and \> 4 for Cohort 2
• Patient must be able to lie still in full body cast for 45 minutes
• Must have a suitable donor defined as a sibling matched at 5/6 or 6/6 antigens (human leukocyte antigen \[HLA\]-A, B, and DRB1) or an unrelated volunteer matched at 7/8 or 8/8 HLA alleles (HLA-A, B, C, and DRB1)
• Signed informed consent
• DONOR: "High resolution" typing at HLA-A, B, C and DRB1 alleles
• Single antigen mismatch for siblings and single allele mismatch for volunteer unrelated donors is acceptable
• Donors must be \>= 17 years of age

You may not qualify if:

• Circulating peripheral blood myeloblasts or lymphoblasts on morphologic analysis from time of last treatment to time of enrollment
• Prior allograft or prior autograft
• Active CNS disease as identified by positive CSF cytospin at time of enrollment
• Karnofsky performance score \< 70
• Symptomatic uncontrolled coronary artery disease or ejection fraction \< 40%
• Total bilirubin \>= 2 x the upper limit of normal
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \>= 3 x the upper limit of normal
• Diffusion capacity of the lung for carbon monoxide (DLCO) \< 40%
• Forced expiratory volume in one second (FEV1) \< 50% (corrected for hemoglobin)
• Receiving supplementary continuous oxygen
• Creatinine clearance \< 50 mL/min/1.73m\^2
• Patients with active uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms)
• Patients seropositive for the human immunodeficiency virus (HIV)
• Females who are pregnant or breastfeeding
• Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment

Sponsors & Collaborators

• Sumithira Vasu: lead

Study Sites (1)

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Congenital Abnormalities; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute

Interventions

Radiotherapy; Radiation; Cyclophosphamide; Antilymphocyte Serum; thymoglobulin; Tacrolimus; Methotrexate; merphos; Transplantation; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; 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

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Macrolides; Lactones; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Surgical Procedures, Operative; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy

Study Officials

• Sumithira Vasu, MD

  Ohio State University 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 INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 22, 2014
• First Posted: April 24, 2014
• Study Start: July 27, 2015
• Primary Completion: September 6, 2022
• Study Completion: September 6, 2022
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)