Giving Chemotherapy for a Shortened Amount of Time Before a Stem Cell Transplantation

NCT04098393 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 19-245
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see if a condensed version of the chemotherapy regimen busulfan, melphalan, fludarabine (bu/mel/flu) and the drug antithymocyte globulin (ATG-also referred to as rATG or thymoglobulin) can have the same or fewer number of severe side effects in people with various blood cancers 30 days after they receive an allogeneic hematopoietic cell transplantation.

Conditions

Hematologic Malignancies

Keywords

Busulfan; Melphalan; Fludarabine; Allogeneic Hematopoietic Cell Transplantation; 19-245

Outcome Measures

Primary Outcomes (1)

• the number of grade 4 toxicities

  All grade 4 CTCAEv5.0 toxicities are included except for hematologic toxicities that are considered expected for patients receiving myeloablative conditioning.

  in the first 30 days post-HCT

Study Arms (2)

patients hematologic malignancies other than multiple myeloma

EXPERIMENTAL

A. Busulfan 3.2 mg/kg/day, with dose adjustments made according to pharmacokinetic (PK) levels. B. Melphalan (70mg/m2/day) administered on days -6 and -5. C. Fludarabine (25mg/m2/ day) administered on days -6, -5, -4, -3, and -2. All patients receiving matched related or unrelated donor allografts receive anti-thymocyte globulin (ATG) 2.5 mg/kg/day on days -3 and -2 to deplete chemotherapy resistant host T-cells that could hinder engraftment, and it may provide additional GVHD prophylaxis.

Drug: Busulfan 3.2 mg/kg/day; Drug: Fludarabine; Drug: Melphalan; Drug: Antithymocyte globulin (ATG); Procedure: Allogeneic hematopoietic cell transplantation (Allo-HCT)

patients with multiple myeloma

EXPERIMENTAL

A. Busulfan 0.8 mg/kg every 6 hours x 10 doses, with dose adjustments made according to PK levels. B. Melphalan (70 mg/m2/day) administered on days -6 and -5. C. Fludarabine (25 mg/m2/day) administered on days -6, -5, -4, -3, -2. All patients receiving matched related or unrelated donor allografts receive anti-thymocyte globulin (ATG) 2.5 mg/kg/day on days -3 and -2 to deplete chemotherapy resistant host T-cells that could hinder engraftment, and it may provide additional GVHD prophylaxis.

Drug: Fludarabine; Drug: Melphalan; Drug: Antithymocyte globulin (ATG); Drug: Busulfan 0.8 mg/kg; Procedure: Allogeneic hematopoietic cell transplantation (Allo-HCT)

Interventions

Busulfan 3.2 mg/kg/day DRUG

Busulfan 3.2 mg/kg/day, with dose adjustments made according to pharmacokinetic (PK) levels.

patients hematologic malignancies other than multiple myeloma

Fludarabine DRUG

Fludarabine (25mg/m2/ day) administered on days -6, -5, -4, -3, and -2.

patients hematologic malignancies other than multiple myeloma; patients with multiple myeloma

Melphalan DRUG

Melphalan (70mg/m2/day) administered on days -6 and -5.

patients hematologic malignancies other than multiple myeloma; patients with multiple myeloma

Antithymocyte globulin (ATG) DRUG

ATG will be given based on a dynamic nomogram based on the patient's absolute lymphocyte count at the start of conditioning and can result in 2 or 3 days of ATG administration.

patients hematologic malignancies other than multiple myeloma; patients with multiple myeloma

Busulfan 0.8 mg/kg DRUG

Busulfan 0.8 mg/kg every 6 hours x 10 doses, with dose adjustments made according to PK levels.

patients with multiple myeloma

Allogeneic hematopoietic cell transplantation (Allo-HCT) PROCEDURE

Allogeneic hematopoietic cell transplantation following the conditioning regimen.

patients hematologic malignancies other than multiple myeloma; patients with multiple myeloma

Eligibility Criteria

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

You may qualify if:

• Patients aged ≥ 18 years old.
• Patients with any of the following hematologic malignancies for which allo-HCT is indicated, including:
• Acute myeloid leukemia (AML) with intermediate or high-risk features in CR1.
• Relapsed AML in ≥ CR2.
• Acute leukemias of ambiguous lineage in ≥ CR1.
• Acute lymphoid leukemia (ALL) in CR1 with clinical, flow cytometric, or molecular features indicating a high risk for relapse, or ALL in ≥ CR2.
• CML meeting one of the following criteria:
• Failed response to or intolerant to BCR-ABL tyrosine kinase inhibitors (TKIs).
• CML with BCR-ABL mutation consistent with poor response to TKIs (e.g., T315I mutation)
• CML in accelerated phase or blast crisis with \<10% blasts after therapy, or in second chronic phase.
• Myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), or MDS/MPN overlap syndromes with least one of the following:
• Revised International Prognostic Scoring System risk score of intermediate or higher at the time of transplant evaluation.
• Life-threatening cytopenias.
• Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype.
• Therapy related disease or disease evolving from other malignant processes.

You may not qualify if:

• Patients with active extramedullary disease.
• Patients with active central nervous system malignancy.
• Active and/or uncontrolled infection at the time of allo-HCT.
• Patients who have undergone previous allo-HCT.
• Patient seropositivity for HIV I/II and/or HTLV I/II.
• Females who are pregnant or breastfeeding.
• Patients unwilling to use contraception during the study period.
• Patient or guardian unable to give informed consent or unable to comply with the treatment protocol.
• Must be a 10/10 HLA genotypically matched related or unrelated donor at A, B, C, DRB1, and DQB1 loci, as tested by DNA analysis.
• Able to provide informed consent for the donation process per institutional standards.
• Meet standard criteria for donor collection as defined by the National Marrow Donor Program Guidelines.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Busulfan; fludarabine; Melphalan; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• Michael Scordo, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a pilot study in which adult patients with hematologic malignancies undergoing ex-vivo CD34-selected allo-HCT will receive a condensed version of our standard bu/mel/flu regimen, reducing the length of the conditioning regimen from 8 days to 5 days.

Study Record Dates

• First Submitted: September 19, 2019
• First Posted: September 23, 2019
• Study Start: September 18, 2019
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: June 29, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)