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Adult Acute Lymphoblastic Leukemia in Complete RemissionPhase 1NCT02446964

Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Leukemia

A Phase 1 study testing Bone Marrow Transplantation, Cyclophosphamide and Fludarabine Phosphate in people with Adult Acute Lymphoblastic Leukemia in Complete Remission and Acute Myeloid Leukemia in Remission, run by City of Hope Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I trial studies the side effects and best dose of total bone marrow and lymphoid irradiation when given together with chemotherapy before donor stem cell transplant in treating patients with myelodysplastic syndrome or acute leukemia. Read more about this study

Who is it for?
Ages 12 to 60 years
What is being tested?
Bone Marrow Transplantation, Cyclophosphamide and Fludarabine Phosphate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteUnited States
Study dates
25 Jun 2015to 20 May 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Eligible patients will have a histopathologically confirmed diagnosis of hematologic malignancy in one of the following categories:
  • Acute myelogenous leukemia
  • In first complete remission (CR1) with poor risk cytogenetics according to National Comprehensive Cancer Network (NCCN) guidelines for acute myeloid leukemia (AML): monosomal karyotype, -5, 5q-,-7,7q-, inv (3), t(3;3), t(6;9), t(9;22) and complex karyotypes (>= 3 unrelated abnormalities [abn]) and normal cytogenetics with fms-related tyrosine kinase 3 (FLT3)-internal tandem duplications (ITD) mutation
  • In pediatrics, all of the above and 11q23-non t(9;11)
  • In second complete remission (CR2) or third complete remission (CR3)
  • With chemosensitive primary refractory disease
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  • Acute lymphocytic leukemia
  • In CR1 with poor risk cytogenetics:
  • For adults according to NCCN guidelines for acute lymphoblastic leukemia (ALL): hypoploidy (< 44 chromosomes); t(v;11q23): mixed lineage leukemia (MLL) rearranged; t(9;22) (q34;q11.2); complex cytogenetics (5 or more chromosomal abnormalities); high white blood cell (WBC) at diagnosis (>= 30,000 for B lineage or >= 50,000 for T lineage)
  • For pediatrics t(9;22), intrachromosomal amplification of chromosome 21 (iAMP21)loss of 13q, and abnormal 17p
  • In CR2 or CR3
  • With chemosensitive primary refractory disease
  • Myelodysplastic syndrome in high-intermediate (int-2) and high risk categories
  • Karnofsky or Lansky performance status >= 80
  • A pretreatment measured creatinine clearance (absolute value) of >= 50 ml/minute
  • Serum bilirubin =< 2.0 mg/dl
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 2.5 times the institutional upper limits of normal
  • Ejection fraction measured by echocardiogram or multigated acquisition scan (MUGA) >= 50%
  • Diffusing capacity of the lung for carbon monoxide (DLCO) and forced expiratory volume in one second (FEV1) > 60% predicted
  • 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
  • The recipient must have a related donor genotypically human leukocyte antigen (HLA)-A, B,C and DRB1 loci haploidentical to the recipient
  • No HLA matched sibling or matched unrelated donor is available
  • Patients should be off all previous intensive therapy, chemotherapy or radiotherapy for 3 weeks prior to commencing therapy on this study
  • (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, quizartinib, midostaurin can also be given up to 3 days before conditioning regimen)
  • Adequate organ function
  • All subjects must have the ability to understand and the willingness to sign a written informed consent
  • Prior radiation therapy that would exclude the use of TMLI
  • DONOR ELIGIBILITY CRITERIA:
  • DONOR: Age =< 60 years of age
  • DONOR: For younger donors, no more than 20 mL bone marrow may be harvested per kg of donor body weight
  • DONOR: Medical history and physical examination confirm good health status as defined by institutional standards
  • DONOR: Seronegative for human immunodeficiency virus (HIV) antigen (Ag), HIV 1+2 antibody (Ab), human T-lymphotropic virus (HTLV) I/II Ab, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) (immunoglobulin [Ig]M and IgG), hepatitis C virus (HCV) Ab, rapid plasma reagin (RPR) for syphilis within 30 days of apheresis collection
  • DONOR: Genotypically haploidentical as determined by HLA typing, preferably a non-maternal HLA haploidentical relative; eligible donors include biological parents, siblings or half siblings, or children
  • DONOR: Female donors of child-bearing potential must have a negative serum or urine beta-human chorionic gonadotropin (HCG) test within three weeks of mobilization
  • DONOR: The donor must have been informed of the investigational nature of this study and have signed a consent form in accordance with federal guidelines and the guidelines of the participating institution
  • DONOR: Selection of a haploidentical donor will require absence of pre-existing donor-directed anti-HLA antibodies in the recipient

Who cannot join

  • Patients should not have any uncontrolled illness including ongoing or active bacterial, viral or fungal infection
  • Patients 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, quizartinib, midostaurin can also be given up to 3 days before conditioning regimen)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to any in the pre- or post-transplant regimen
  • Pregnant women are excluded from this study
  • Patients with other active malignancies are ineligible for this study, other than non-melanoma skin cancers
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  • The recipient has a medical problem or neurologic/psychiatric dysfunction which would impair his/her ability to be compliant with the medical regimen and to tolerate transplantation or would prolong hematologic recovery which in the opinion of the principal investigator would place the recipient at unacceptable risk
  • Patients may not have had a prior autologous or allogeneic transplant
  • HLA-matched or partially matched (7/8 or 8/8) related or unrelated donor is available to donate
  • Patients may not have received more than 3 prior regimens, where the regimen intent was to induce remission
  • Patients treatment history may not include anti-CD33 monoclonal antibody therapy (e.g., SGN-CD33 or Mylotarg)
  • Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
  • DONOR EXCLUSION CRITERIA:
  • DONOR: Evidence of active infection
  • DONOR: Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis
  • DONOR: Factors which place the donor at increased risk for complications from leukapheresis or granulocyte-colony stimulating factor (G-CSF) therapy
  • DONOR: HIV positive

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: Phase I Study of Escalating Doses of Total Marrow and Lymphoid Irradiation (TMLI) During Conditioning for HLA-Haploidentical Hematopoietic Cell Transplantation With Post-Transplant Cyclophosphamide in Patients With Myelodysplasia or Acute Leukemia

This phase I trial studies the side effects and best dose of total bone marrow and lymphoid irradiation when given together with chemotherapy before donor stem cell transplant in treating patients with myelodysplastic syndrome or acute leukemia. Total marrow and lymphoid irradiation is a type of radiation therapy that targets bone marrow and blood, where the cancer is, instead of applying radiation to the whole body. Stem cell transplants use high doses of chemotherapy and radiation therapy, such as total marrow and lymphoid irradiation, to kill cancer cells, but these treatments kill normal cells as well. After chemotherapy, healthy cells from a donor are given to the patient to help the patient grow new blood cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To establish safety and determine the maximum tolerated dose of total marrow and lymphoid irradiation when given in combination with fludarabine (fludarabine phosphate) and pre-post-transplant cyclophosphamide, as conditioning for haploidentical hematopoietic cell transplantation (HCT) in patients with high-risk acute lymphocytic or myelogenous leukemia or intermediate/high-risk myelodysplastic syndrome.

II. To evaluate the safety of the regimen at each dose level by assessing adverse events: type, frequency, severity, attribution, time course, duration.

III. To evaluate the safety of the regimen at each dose level by assessing complications: including acute/chronic graft-versus-host disease (GvHD), infection and delayed engraftment.

SECONDARY OBJECTIVES:

  1. To estimate overall survival (OS), progression-free survival (PFS), cumulative incidence (CI) of relapse/progression, and non-relapse mortality (NRM) at +100 Days, 1 year and 2 years.

II. To characterize minimal residual disease from bone marrow aspirates on Days +30, +100, +180 post-transplant and describe in relation to total marrow and lymphoid irradiation (TMLI) dose level and patient disease status.

III. To describe the kinetics of immune cell recovery in the first year post-transplantation.

OUTLINE: This is a dose-escalation study of TMLI.

CONDITIONING: Patients undergo TMLI twice daily (BID) on days -7 to -4 or -3 (depending on the dose level). Patients also receive fludarabine phosphate intravenously (IV) on days -7 to -3 and cyclophosphamide IV on days -7, -6, 3, and 4.

TRANSPLANT: Patients undergo bone marrow or peripheral blood stem cell transplant on day 0.

GHVD PROPHYLAXIS: Patients receive tacrolimus* IV once daily (QD) or orally (PO) BID on days 5-180. Patients also receive mycophenolate mofetil PO thrice daily (TID) or IV on days 5-35. Treatment with tacrolimus and mycophenolate mofetil may continue in the presence of active GVHD.

*NOTE: Patients intolerant of tacrolimus may receive cyclosporine.

After completion of study treatment, patients are followed up twice weekly for 100 days, twice monthly until 6 months, monthly until the patient is off immunosuppressive therapy without evidence of GVHD, and then at least yearly for a total of 5 years.

Being tested
Bone Marrow Transplantation, Cyclophosphamide, Fludarabine Phosphate, Laboratory Biomarker Analysis, Mycophenolate Mofetil
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bone Marrow TransplantationProcedure or surgery

    Also called BMT, Bone Marrow Grafting, Bone Marrow Transplant, Marrow Transplantation

    Undergo bone marrow transplant

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given PO or IV

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

    Undergo peripheral blood stem cell transplant

  • TacrolimusDrug

    Also called FK 506, Fujimycin, Prograf, Protopic

    Given IV and PO

  • Total Marrow IrradiationRadiation

    Undergo TMLI

Study groups in NCT02446964
Study groupRoleWhat they receive
Treatment (TMLI, chemotherapy, transplant, GVHD prophylaxis)ExperimentalCONDITIONING: Patients undergo TMLI BID on days -7 to -4 or -3 (depending on the dose level). Patients also receive fludarabine phosphate IV on days -7 to -3 and cyclophosphamide IV on days -7, -6, 3, and 4. TRANSPLANT: Patients undergo bone marrow or peripheral blood stem cell transplant on day 0. GHVD PROPHYLAXIS: Patients receive tacrolimus* IV QD or PO BID on days 5-180. Patients also receive mycophenolate mofetil PO TID or IV on days 5-35. Treatment with tacrolimus and mycophenolate mofetil may continue in the presence of active GVHD. *NOTE: Patients intolerant of tacrolimus may receive cyclosporine.
Receives: Procedure: Bone Marrow Transplantation; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Tacrolimus; Radiation: Total Marrow Irradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose-limiting toxicity (DLT) scored on both the Bearman Scale and National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03

    Toxicity information recorded will include the type, severity, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.

    Measured: Up to 100 days

  2. Maximum tolerated dose of TMLI when given in combination with fludarabine phosphate and cyclophosphamide, defined as the highest dose where 6 patients have been treated and at most one patient experiences DLT

    Toxicity information recorded will include the type, severity, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.

    Measured: Up to day -3

Secondary outcomes (10)

  1. Complete remission proportion

    Measured: At day 30

  2. Immune reconstitution of B, T and NK cells

    Measured: Up to 1 year

  3. Incidence of acute GVHD of grades 2-4 and 3-4

    The cumulative incidence of relapse/progression, non-relapse mortality and acute/chronic GVHD will be calculated as competing risks.

    Measured: Within the first 100 days post-transplant

  4. Incidence of chronic GVHD

    The cumulative incidence of relapse/progression, non-relapse mortality and acute/chronic GVHD will be calculated as competing risks.

    Measured: After 180 days post-transplant assessed up to 5 years

  5. Incidence of infection

    Microbiologically documented infections will be reported by site of disease, date of onset, severity and resolution, if any.

    Measured: Up to day 100

  6. Minimal residual disease

    Measured: Up to 180 days post-transplant

  7. Non-relapse mortality (NRM)

    The cumulative incidence of relapse/progression, non-relapse mortality and acute/chronic GVHD will be calculated as competing risks.

    Measured: Up to 5 years

  8. Overall survival

    Survival estimates will be calculated using the Kaplan-Meier method.

    Measured: Time from start of protocol therapy to death, or last follow-up, whichever comes first, assessed up to 5 years

  9. Progression-free survival

    Survival estimates will be calculated using the Kaplan-Meier method.

    Measured: Time from start of protocol therapy to death, relapse/progression, or last follow-up, whichever comes first, assessed up to 5 years

  10. Incidence of grade 3-5 adverse events per CTCAE v4.03

    Toxicity information recorded will include the type, severity, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.

    Measured: Up to 100 days post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2015 (estimated)
  2. Study start25 Jun 2015
  3. Primary completion20 May 2025
  4. Study completion20 May 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02446964
Sponsor's protocol ID
14106
Other IDs
NCI-2015-00788, 114382, 14106
Status last verified
Jun 2025
First submitted
14 May 2015
Last updated
22 Jun 2025
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bone Marrow Transplantation, Cyclophosphamide and Fludarabine Phosphate in people with Adult Acute Lymphoblastic Leukemia in Complete Remission and Acute Myeloid Leukemia in Remission, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose-limiting toxicity (DLT) scored on both the Bearman Scale and National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (time frame: Up to 100 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02446964.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2025.

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