Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in With High-Risk Hematologic Malignancies

NCT01760655 | Completed Phase 2 Results DMC FDA Device

• 2 other identifiers: 12D.501JT 2977
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies reduced-intensity conditioning before donor stem cell transplant in treating patients with high-risk hematologic malignancies. Giving low-doses of chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) before the transplant may help increase this effect.

Conditions

Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Gene Mutations; Acute Myeloid Leukemia With Inv(3) (q21.3;q26.2); GATA2, MECOM; Acute Myeloid Leukemia With t(6;9) (p23;q34.1); DEK-NUP214; Aplastic Anemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Follicular Lymphoma; Hodgkin Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Myeloid Leukemia; Non-Hodgkin Lymphoma; Plasma Cell Myeloma; Polycythemia Vera; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival (DFS)

  This hypothesis will be rejected if the 95% confidence interval for year DFS rate computed from the estimated Kaplan-Meier survival curves will be entirely above 0.35.

  1 year post hematopoietic stem cell transplant (HSCT)

Secondary Outcomes (6)

• Overall Survival

  1 year post HSCT

• Overall Survival

  3 years post HSCT

• Immune Reconstitution at Day +28

  Up to 1 year

• Immune Reconstitution at Day +90

  Up to 1 year

• Incidence and Degree of Graft Versus Host Disease

  Up to 1 year

Study Arms (1)

Treatment (RIC and allogeneic PBSCT)

EXPERIMENTAL

REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV on days -15 to -12, busulfan IV on days -14 to -13, DLI on day -6, and cyclophosphamide IV on days -3 and -2. Patients also undergo TBI on day -10. TRANSPLANT: Patients undergo allogeneic PBSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV on days -1 to 42 followed by taper and mycophenolate mofetil IV BID on days -1 to 28

Drug: Fludarabine phosphate; Drug: Busulfan; Radiation: Total-Body Irradiation; Biological: Therapeutic Allogeneic Lymphocytes; Drug: Cyclophosphamide; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Other: Laboratory Biomarker Analysis

Interventions

Fludarabine phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 75607-67-9, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, 2-fluoro-9-(5-O-phosphono-beta-D-arabinofuranosyl), Beneflur, Fludara, Fludarabine-5'-Monophosphate, SH T 586

Treatment (RIC and allogeneic PBSCT)

Busulfan DRUG

Given IV

Also known as: 1, 4-Bis[methanesulfonoxy]butane, 1,4-Bis(methanesulfonoxy)butane, 1,4-Bitanediol Dimethanesulfonate Esters, 1,4-Butanediol Dimethylsulfonate, 1,4-Di(methanesulfonyloxy)butane, 1,4-Di(methylsulfonyloxy)butane, 55-98-1, BUS, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508

Treatment (RIC and allogeneic PBSCT)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: TBI, SCT_TBI, TOTAL BODY IRRADIATION, Whole Body, Whole Body Irradiation, Whole-Body Irradiation

Treatment (RIC and allogeneic PBSCT)

Therapeutic Allogeneic Lymphocytes BIOLOGICAL

Undergo DLI

Also known as: Allogeneic Lymphocytes

Treatment (RIC and allogeneic PBSCT)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 1-bis(2-chloroethyl)-amino-1-oxo-2-aza-5-oxaphosphoridin monohydrate, 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate, 2-[bis(b-chloroethyl)amino]-1-oxa-3-aza-2-phosphacyclohexane-2-oxide monohydrate, 2-[di(chloroethyl)amino]-1-oxa-3-aza-2-phosphacyclohexane 2-oxide monohydrate, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, 6055-19-2, bis(2-chloroethyl)phosphamide cyclic propanolamide ester monohydrate, Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester 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, N,N-bis(2-chloroethyl)-N',O-propylenephosphoric acid ester diamide monohydrate, N,N-bis(2-chloroethyl)-N'-(3-hydroxypropyl)phosphorodiamidic acid intramolecular ester monohydrate, N,N-bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide monohydrate, N,N-bis(b-chloroethyl)-N',O-trimethylenephosphoric acid ester diamide monohydrate, N,N-bis(beta-chloroethyl)-N',O-propylenephosphoric acid ester diamide monohydrate, N,N-bis(beta-chloroethyl)-N',O-trimethylenephosphoric acid ester diamide monohydrate, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (RIC and allogeneic PBSCT)

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSCT

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, allogeneic stem cell transplantation, HSC, HSCT, Stem Cell Transplantation

Treatment (RIC and allogeneic PBSCT)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSCT

Also known as: PBPC transplantation, PBSCT, Peripheral Blood, Peripheral Blood Progenitor Cell Transplantation, PERIPHERAL BLOOD STEM CELL TRANSPLANT, peripheral stem cell support, Peripheral Stem Cell Transplant, peripheral stem cell transplantation

Treatment (RIC and allogeneic PBSCT)

Tacrolimus DRUG

Given IV

Also known as: 109581-93-3, FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (RIC and allogeneic PBSCT)

Mycophenolate Mofetil DRUG

Given IV

Also known as: 115007-34-6, 128794-94-5, Cellcept, MMF

Treatment (RIC and allogeneic PBSCT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (RIC and allogeneic PBSCT)

Eligibility Criteria

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

You may qualify if:

• By definition, patients with hematological malignancies or dyscrasias that require HSCT as part of cure-directed therapy are by definition high-risk and can be treated on this protocol; examples of high risk patients include but are not limited to:
• Acute myeloid leukemia with high risk features as defined by:
• Age greater than or equal to 60
• Secondary acute myeloid leukemia (AML) (prior therapy or hematologic malignancy)
• Normal cytogenetics but fms-related tyrosine kinase 3 (FLT3)/internal tandem duplication (ITD) positive
• Any relapse or primary refractory disease
• Greater than 3 cytogenetic abnormalities or any one of the following cytogenetic abnormalities: -5/del(5q), -7/del(7q), Abn(9q), (11q), (3q), (21q), (17p), t(6;9), t(6;11), t(11;19), +8, del(12p), inv(3), t(10;11), -17, 11q 23
• Any single autosomal monosomy
• Acute lymphoid leukemia in 1st or 2nd morphological remission; ALL with any morphological evidence of disease will not be eligible
• Myelodysplasia (MDS) other than refractory anemia (RA), refractory anemia with rare sideroblasts (RARS), or isolated 5q- syndrome subtypes
• Hodgkin's or Non-Hodgkin's lymphoma in 2nd or greater remission or with persistent disease
• Myeloma with evidence of persistent disease after front-line therapy
• Chronic myeloid leukemia (CML) resistant to signal transducer inhibitor (STI) therapy
• Myelofibrosis and chronic myelomonocytic leukemia (CMML)
• Essential thrombocytopenia or polycythemia vera with current or past evidence of evolution to acute leukemia

You may not qualify if:

• Human immunodeficiency virus (HIV) positive
• Active involvement of the central nervous system with malignancy; this can be documented as a normal neurological exam and/or a negative cerebrospinal fluid (CSF) analysis
• Pregnancy
• Patients with life expectancy of =\< 6 months for reasons other than their underlying hematologic/oncologic disorder
• Patients who have received alemtuzumab or ATG within 8 weeks of the transplant admission
• Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Sidney Kimmel Cancer Center at Thomas Jefferson University
• Thomas Jefferson University Hospital

MeSH Terms

Conditions

Anemia, Aplastic; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Chronic; Lymphoma, Follicular; Hodgkin Disease; Myelodysplastic Syndromes; Primary Myelofibrosis; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Multiple Myeloma; Polycythemia Vera; Leukemia, Myeloid, Acute

Interventions

fludarabine phosphate; Busulfan; methanesulfonic acid; Whole-Body Irradiation; Cyclophosphamide; Stem Cell Transplantation; Peripheral Blood Stem Cell Transplantation; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Hematopoietic Stem Cell Transplantation; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Dolores Grosso
• Organization: Tevogen Bio

dolores.grosso@tevogen.com

848-256-5751

Study Officials

• Dolores Grosso, RN, CRNP, DNP

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

• Neal Flomenberg, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2013
• First Posted: January 4, 2013
• Study Start: December 24, 2012
• Primary Completion: April 15, 2022
• Study Completion: December 5, 2022
• Last Updated: October 30, 2025
• Results First Posted: October 30, 2025

Record last verified: 2025-10

Locations

US (1)