Bendamustine With or Without Cyclophosphamide in Preventing GVHD in Patients Undergoing Stem Cell Transplant

NCT ID: NCT04022239

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-13
• Study Completion Date: 2027-07-31

Brief Summary

This phase I/II trial studies the side effects and best dose of bendamustine when given with or without cyclophosphamide in preventing graft versus host disease (GVHD) in patients undergoing stem cell transplant. Drugs used in chemotherapy, such as bendamustine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy and total body irradiation before or after a stem cell transplant helps kills cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Sometimes, the transplanted cells from a donor can attack the body's normal cells called GVHD. Giving tacrolimus, mycophenolate mofetil, and filgrastim after the transplant may stop this from happening.

Detailed Description

PRIMARY OBJECTIVE:

I. Evaluate the safety of substituting the standard post-transplant cyclophosphamide (PT-CY) given on day +3 and +4 with post-transplant bendamustine (PT-BEN) in patients undergoing HLA-mismatched hematopoietic cell transplantation.

SECONDARY OBJECTIVES:

I. To evaluate treatment-related mortality. II. To assess acute and chronic graft-versus-host disease (GVHD). III. To assess overall survival, progression-free survival and relapse rates. IV. To evaluate the risk of acute cystitis. V. To evaluate immune reconstitution after transplantation.

OUTLINE: This is a dose-escalation study of bendamustine. Patients are assigned to 1 of 2 treatment schedules.

SCHEDULE I (NON-LYMPHOMA): Patients receive fludarabine intravenously (IV) over 1 hour on days -5 to -2, melphalan IV over 30 minutes on days -5 and -4, and undergo total body irradiation (TBI) on day -1 and stem cell transplantation IV over 2-6 hours on day 0. Depending on when the trial was joined, patients receive cyclophosphamide IV over 3 hours or bendamustine IV over 30-60 minutes or cyclophosphamide IV over 3 hours and bendamustine IV over 30-60 minutes on day 3. Patients also receive bendamustine IV over 30-60 minutes on day 4. Beginning day 5, patients receive tacrolimus IV followed by orally (PO) once daily (QD) or twice daily (BID) for 6 months and mycophenolate mofetil PO thrice daily (TID) until day 100. Beginning day 7, patients receive filgrastim-sndz subcutaneously (SC) QD until blood cell levels return to normal.

SCHEDULE II (LYMPHOID MALIGNANCIES): Patients receive fludarabine IV over 1 hour, bendamustine IV over 30-60 minutes on days -5 to -3 and undergo TBI on day -1 and stem cell transplantation over 2-6 hours on day 0. Depending on when the trial was joined, patients receive cyclophosphamide IV over 3 hours or bendamustine IV over 30-60 minutes or cyclophosphamide IV over 3 hours and bendamustine IV over 30-60 minutes on day 3. Patients also receive bendamustine IV over 30-60 minutes on day 4. Beginning day 5, patients receive tacrolimus IV followed by PO QD or BID for 6 months and mycophenolate mofetil PO TID until day 100. Beginning day 7, patients receive filgrastim-sndz SC QD until blood cell levels return to normal. CD20+ patients receive rituximab IV over 4-6 hours on days -13, -6, 1, and 8.

After completion of study treatment, patients are followed weekly for 3 months, every 3 months in year 1, and every 6 months in year 2.

Conditions

Hematopoietic and Lymphoid System Neoplasm

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Schedule I (non-lymphoma)

Patients receive fludarabine IV over 1 hour on days -5 to -2, melphalan IV over 30 minutes on days -5 and -4, and undergo TBI on day -1 and stem cell transplantation IV over 2-6 hours on day 0. Depending on when the trial was joined, patients receive cyclophosphamide IV over 3 hours or bendamustine IV over 30-60 minutes or cyclophosphamide IV over 3 hours and bendamustine IV over 30-60 minutes on day 3. Patients also receive bendamustine IV over 30-60 minutes on day 4. Beginning day 5, patients receive tacrolimus IV followed by PO QD or BID for 6 months and mycophenolate mofetil PO TID until day 100. Beginning day 7, patients receive filgrastim-sndz SC QD until blood cell levels return to normal.

Group Type: EXPERIMENTAL

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type: PROCEDURE

Undergo stem cell transplantation

Bendamustine

Intervention Type: DRUG

Given IV

Cyclophosphamide

Intervention Type: DRUG

Given IV

Filgrastim-sndz

Intervention Type: BIOLOGICAL

Given SC

Fludarabine

Intervention Type: DRUG

Given IV

Melphalan

Intervention Type: DRUG

Given IV

Mycophenolate Mofetil

Intervention Type: DRUG

Given PO

Tacrolimus

Intervention Type: DRUG

Given IV and PO

Total-Body Irradiation

Intervention Type: RADIATION

Undergo TBI

Schedule II (lymphoid malignancies)

Patients receive fludarabine IV over 1 hour, bendamustine IV over 30-60 minutes on days -5 to -3 and undergo TBI on day -1 and stem cell transplantation over 2-6 hours on day 0. Depending on when the trial was joined, patients receive cyclophosphamide IV over 3 hours or bendamustine IV over 30-60 minutes or cyclophosphamide IV over 3 hours and bendamustine IV over 30-60 minutes on day 3. Patients also receive bendamustine IV over 30-60 minutes on day 4. Beginning day 5, patients receive tacrolimus IV followed by PO QD or BID for 6 months and mycophenolate mofetil PO TID until day 100. Beginning day 7, patients receive filgrastim-sndz SC QD until blood cell levels return to normal. CD20+ patients receive rituximab IV over 4-6 hours on days -13, -6, 1, and 8.

Group Type: EXPERIMENTAL

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type: PROCEDURE

Undergo stem cell transplantation

Bendamustine

Intervention Type: DRUG

Given IV

Cyclophosphamide

Intervention Type: DRUG

Given IV

Filgrastim-sndz

Intervention Type: BIOLOGICAL

Given SC

Fludarabine

Intervention Type: DRUG

Given IV

Mycophenolate Mofetil

Intervention Type: DRUG

Given PO

Rituximab

Intervention Type: BIOLOGICAL

Given IV

Tacrolimus

Intervention Type: DRUG

Given IV and PO

Total-Body Irradiation

Intervention Type: RADIATION

Undergo TBI

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation

Undergo stem cell transplantation

Intervention Type: PROCEDURE

Bendamustine

Given IV

Intervention Type: DRUG

Cyclophosphamide

Given IV

Intervention Type: DRUG

Filgrastim-sndz

Given SC

Intervention Type: BIOLOGICAL

Fludarabine

Given IV

Intervention Type: DRUG

Melphalan

Given IV

Intervention Type: DRUG

Mycophenolate Mofetil

Given PO

Intervention Type: DRUG

Rituximab

Given IV

Intervention Type: BIOLOGICAL

Tacrolimus

Given IV and PO

Intervention Type: DRUG

Total-Body Irradiation

Undergo TBI

Intervention Type: RADIATION

Other Intervention Names

Allogeneic; Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation, Allogeneic; SDX-105; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, 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; Neosar; Revimmune; Syklofosfamid; WR- 138719; Filgrastim Biosimilar Filgrastim-sndz; Zarxio; Fluradosa; 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; CellCept; MMF; ABP 798; BI 695500; C2B8 Monoclonal Antibody; Chimeric Anti-CD20 Antibody; CT-P10; IDEC-102; IDEC-C2B8; IDEC-C2B8 Monoclonal Antibody; MabThera; Monoclonal Antibody IDEC-C2B8; PF-05280586; Rituxan; Rituximab ABBS; Rituximab Biosimilar ABP 798; Rituximab Biosimilar BI 695500; Rituximab Biosimilar CT-P10; Rituximab Biosimilar GB241; Rituximab Biosimilar IBI301; Rituximab Biosimilar JHL1101; Rituximab Biosimilar PF-05280586; Rituximab Biosimilar RTXM83; Rituximab Biosimilar SAIT101; Rituximab Biosimilar SIBP-02; rituximab biosimilar TQB2303; rituximab-abbs; RTXM83; Truxima; FK 506; Fujimycin; Hecoria; Prograf; Protopic; SCT_TBI; TBI; Total Body Irradiation; Whole Body Irradiation; Whole-Body Irradiation

Eligibility Criteria

Inclusion Criteria

• Patient with hematologic malignancies.
• Donor: Matched sibling, matched unrelated, mismatched or haploidentical
• Zubrod performance 0 to 2 or Karnofsky of at least 60.
• Adequate organ function at time of study entry:

1. Creatinine less than or equal to 1.6 mg/dL and creatinine clearance >/= 30 ml/min. Creatinine clearance will be calculated using the Cockcroft-Gault equation

2. Total bilirubin less than < 1.5 x UNL

3. SGPT < 2.5 x ULN

4. Ejection fraction >/= 40%

5. FEV1, FVC and DLCO >/= 40%

• Female patients of childbearing potential must agree to use an effective method of birth control while on study and for 6 months after the last dose of bendamustine. Male patients with female partners of childbearing potential must agree to use an effective method of birth control while on study and for 3 months after the last dose of bendamustine.

Exclusion Criteria

• Pregnant or nursing women.
• Known to be HIV positive
• Active and uncontrolled disease/infection
• Unable or unwilling to sign consent
• Current active hepatic or biliary disease (with exception of Gilbert's syndrome)
• Active hepatitis B or C.
• Toxicities (grade > 1) unresolved from prior treatment (including chemotherapy, targeted therapy, immunotherapy, experimental agents radiation, or surgery.
• Patients with standard risk acute leukemia in first complete remission and patients with chronic myeloid leukemia in first chronic will be excluded during escalated phase.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Issa F Khouri

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

M D Anderson Cancer Center

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Issa F. Khouri, M D

Role: CONTACT

ikhouri@mdanderson.org

713-745-0049

Facility Contacts

Issa F. Khouri

Role: primary

ikhouri@mdanderson.org

713-745-0049

Related Links

http://www.mdanderson.org

M D Anderson Cancer Center

Other Identifiers

NCI-2019-03900

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018-0972

Identifier Type: OTHER

Identifier Source: secondary_id

2018-0972

Identifier Type: -

Identifier Source: org_study_id