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

NCT04022239 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2018-0972NCI-2019-03900
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematopoietic and Lymphoid System Neoplasm

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose level (MTDL) (Phase I)

  Will employ the time-to-event Bayesian optimal interval design to find the MTDL. After the trial is completed, the MTDL will be selected based on isotonic regression as specified in Yuan et al. Specifically, MTDL will be selected as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate. If there are ties, the higher dose level when the isotonic estimate is lower than the target toxicity rate will be selected and the lower dose level when the isotonic estimate is greater than or equal to the target toxicity rate will be selected.

  Up to 30 days

• Dose-limiting toxicity (Phase I)

  Up to 100 days

• Incidence of adverse events (Phase II)

  The trial is continuously monitored for toxicity per the statistical design.

  Up to 2 years

Study Arms (2)

Schedule I (non-lymphoma)

EXPERIMENTAL

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.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Bendamustine; Drug: Cyclophosphamide; Biological: Filgrastim-sndz; Drug: Fludarabine; Drug: Melphalan; Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Radiation: Total-Body Irradiation

Schedule II (lymphoid malignancies)

EXPERIMENTAL

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.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Bendamustine; Drug: Cyclophosphamide; Biological: Filgrastim-sndz; Drug: Fludarabine; Drug: Mycophenolate Mofetil; Biological: Rituximab; Drug: Tacrolimus; Radiation: Total-Body Irradiation

Interventions

Bendamustine DRUG

Given IV

Also known as: SDX-105

Schedule I (non-lymphoma); Schedule II (lymphoid malignancies)

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo stem cell transplantation

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Schedule I (non-lymphoma); Schedule II (lymphoid malignancies)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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

Schedule I (non-lymphoma); Schedule II (lymphoid malignancies)

Filgrastim-sndz BIOLOGICAL

Given SC

Also known as: Filgrastim Biosimilar Filgrastim-sndz, Zarxio

Schedule I (non-lymphoma); Schedule II (lymphoid malignancies)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Schedule I (non-lymphoma); Schedule II (lymphoid malignancies)

Melphalan DRUG

Given IV

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

Schedule I (non-lymphoma)

Mycophenolate Mofetil DRUG

Given PO

Also known as: CellCept, MMF

Schedule I (non-lymphoma); Schedule II (lymphoid malignancies)

Rituximab BIOLOGICAL

Given IV

Also known as: 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

Schedule II (lymphoid malignancies)

Tacrolimus DRUG

Given IV and PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Schedule I (non-lymphoma); Schedule II (lymphoid malignancies)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: SCT_TBI, TBI, Total Body Irradiation, Whole Body Irradiation, Whole-Body Irradiation

Schedule I (non-lymphoma); Schedule II (lymphoid malignancies)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• Total bilirubin less than \< 1.5 x UNL
• SGPT \< 2.5 x ULN
• Ejection fraction \>/= 40%
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Interventions

Stem Cell Transplantation; Bendamustine Hydrochloride; Cyclophosphamide; Filgrastim; Granulocyte Colony-Stimulating Factor; fludarabine; Melphalan; Mycophenolic Acid; Rituximab; CT-P10; Tacrolimus; Whole-Body Irradiation

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Caproates; Fatty Acids; Lipids; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Radiotherapy; Investigative Techniques

Study Officials

• Issa F Khouri

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Issa F. Khouri, M D

CONTACT

713-745-0049; ikhouri@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: July 15, 2019
• First Posted: July 17, 2019
• Study Start: March 13, 2020
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: January 12, 2026

Record last verified: 2026-01

Locations

US (1)