Total Marrow and Lymphoid Irradiation, Fludarabine, and Melphalan Before Donor Stem Cell Transplant in Treating Participants With High-Risk Acute Leukemia or Myelodysplastic Syndrome

NCT03494569 | Suspended Phase 1 DMC FDA Drug

• 2 other identifiers: 17505NCI-2018-00497
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I studies the side effects and best dose of total marrow and lymphoid irradiation when given together with fludarabine and melphalan before donor stem cell transplant in treating participants with high-risk acute leukemia or myelodysplastic syndrome. Giving chemotherapy, such as fludarabine and melphalan, and total marrow and lymphoid irradiation before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

Conditions

Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia; Acute Myeloid Leukemia in Remission; Hematopoietic Cell Transplantation Recipient; Minimal Residual Disease; Myelodysplastic Syndrome; Secondary Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Incidence of toxicity

  Toxicity will be scored on both the Bearman scale and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5 scale. Toxicity information recorded in each patient 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, and dose levels in each arm.

  Up to 2 years

Secondary Outcomes (13)

• Overall survival

  From start of protocol therapy up to 2 years

• Event-free survival

  From start of protocol therapy up to 2 years

• Relapse/progression

  From start of protocol therapy up to 2 years

• Complete remission proportion

  At day 30

• Non-relapse mortality

  Up to 2 years

Study Arms (1)

Treatment (TMLI, fludarabine, melphalan)

EXPERIMENTAL

Participants undergo TMLI BID on days -8 to -5, and receive fludarabine IV on days -4 to -2 and melphalan on day -2. Participants then undergo alloHCT on day 0.

Drug: Fludarabine; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Radiation: Total Marrow Irradiation

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (TMLI, fludarabine, melphalan)

Total Marrow Irradiation RADIATION

Undergo TMLI

Treatment (TMLI, fludarabine, melphalan)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (TMLI, fludarabine, melphalan)

Melphalan DRUG

Given as per City of Hope Standard Operating Procedure

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine nitrogen mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment (TMLI, fludarabine, melphalan)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible patients with a histopathological confirmed diagnosis of hematologic malignancy in one of the following categories:
• Acute myelogenous leukemia:
• Patients with de novo or secondary disease in unfavorable risk group including poor risk cytogenetics according to National Comprehensive Cancer Network (NCCN) guidelines for AML i.e., monosomal karyotype, -5, 5q-, -7, 7q-, 11q23-non t (9;11), inv (3), t (3;3),t (6;9), t (9;22) and complex karyotypes (≥ 3 unrelated abnormalities), or all patient in intermediate risk groups accept patients with FLT3-NPM1+ disease
• Patients with active disease
• Patients with chemosensitive active disease
• Acute lymphocytic leukemia:
• Patients with de novo or secondary disease according to NCCN guidelines for ALL hypoploidy (\< 44 chromosomes); t (v;11q23): 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); iAMP21loss of 13q, and abnormal 17p
• Patients with active disease
• Patients with chemosensitive active disease
• Myelodysplastic syndrome in high-intermediate (int-2) and high risk categories
• Patients ≥ 12 years and \< 55 years are also included if they are not candidates for myeloablative conditioning regimens due to comorbidities
• Karnofsky or Lansky performance status of ≥ 70
• A pretreatment measured creatinine clearance (absolute value) of ≥ 60 ml/minute
• Patients must have a serum bilirubin ≤ 2.0 mg/dl
• Serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) ≤ 2.5 times the institutional upper limits of normal

You may not qualify if:

• Having any uncontrolled illness including ongoing or active bacterial, viral or fungal infection
• Receiving any investigational agents or concurrent biological, intensive chemotherapy or radiation therapy for the previous 2 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 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 regimen
• Patients with other malignancies are ineligible for this study, other than non-melanoma skin cancers
• The recipient has another 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 in which the opinion of the principal investigator would place the recipient at unacceptable risk
• Patients may not have had a prior autologous or allogeneic transplant
• Patients may not have received more than 3 prior lines of intensive chemotherapy, where the regimen intent was to induce remission
• In the opinion of the principal investigator (PI), the participant has a condition that will preclude them from complying with study treatment
• 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
• All subjects must have the ability to understand and the willingness to sign a written informed consent; they are to give voluntary written informed consent before performance if any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care; cognitively impaired subjects will be included only if their guardian or legal representative agrees to sign the written informed consent
• DONOR: Donor selection for both arms must be approved by the donor selection committee
• DONOR: Evidence of active infection
• DONOR: Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy or leukapheresis
• DONOR: Factors which place the donor at increased risk for complications from leukapheresis or granulocyte-colony stimulating factor (G-CSF) therapy could be harvested for bone marrow (BM) if safer for the donor and if approved by the principal investigator (PI)

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; Neoplasm, Residual; Myelodysplastic Syndromes

Interventions

fludarabine; Melphalan

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Monzr Al Malki

  City of Hope Medical 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: April 4, 2018
• First Posted: April 11, 2018
• Study Start: July 6, 2018
• Primary Completion (Estimated): June 11, 2026
• Study Completion (Estimated): June 11, 2026
• Last Updated: March 18, 2026

Record last verified: 2026-03

Locations

US (1)