Gemcitabine Hydrochloride, Clofarabine, and Busulfan Before Donor Stem Cell Transplant in Treating Patients With Refractory B-Cell or T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma

NCT01701986 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2012-0506NCI-2012-02055
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of gemcitabine hydrochloride, clofarabine, and busulfan before donor stem cell transplant and to see how well it works in treating patients with B-cell or T-cell non-Hodgkin lymphoma or Hodgkin lymphoma that does not respond to treatment. Giving chemotherapy before a donor bone marrow or peripheral blood 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. 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

Hematopoietic Cell Transplantation Recipient; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Optimal Dose of Gemcitabine Hydrochloride Determined by Dose Limiting Toxicity

  Dose limiting toxicity is defined as number of participants experienced grade 3-4 mucositis lasting for more than 3 days at peak severity, grade 3-4 skin toxicity lasting for more than 3 days at peak severity, occurring within 30 days from transplant, or grade 4 nonhematological/noninfectious toxicity.

  Within 30 days of transplant

• Number of Participants That Had 100 Day Success Rate Post Transplant

  Number of participants that are alive, engrafted, without grade 3-4 GVHD within 100 days post transplant.

  100 days post transplant

Secondary Outcomes (2)

• Overall Survival

  Up to 5 years

• Treatment Related Mortality

  Up to 100 days post-transplant

Study Arms (1)

Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)

EXPERIMENTAL

PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride IV over 40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive antithymocyte globulin IV on days -3 to -1 and patients with CD20-positive disease also receive rituximab IV on days -14, -7, 1, and 8. TRANSPLANT: Patients undergo allogeneic BMT or PBSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO beginning on day -2 for up to 6 months and mycophenolate mofetil IV over 2 hours or PO TID beginning day 0.

Procedure: Allogeneic Bone Marrow Transplantation; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Biological: Anti-Thymocyte Globulin; Drug: Busulfan; Drug: Clofarabine; Drug: Gemcitabine Hydrochloride; Drug: Mycophenolate Mofetil; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Pharmacological Study; Biological: Rituximab; Drug: Tacrolimus

Interventions

Allogeneic Bone Marrow Transplantation PROCEDURE

Undergo allogeneic BMT

Also known as: Allo BMT, Allogeneic BMT

Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic BMT or PBSCT

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

Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)

Anti-Thymocyte Globulin BIOLOGICAL

Given IV

Also known as: Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin

Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)

Busulfan DRUG

Given IV

Also known as: 1, 4-Bis[methanesulfonoxy]butane, 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 (gemcitabine, clofarabine, busulfan, BMT or PBSCT)

Clofarabine DRUG

Given IV

Also known as: Clofarex, Clolar

Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011, LY188011

Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)

Mycophenolate Mofetil DRUG

Given IV then PO

Also known as: Cellcept, MMF

Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSCT

Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)

Pharmacological Study OTHER

Correlative studies

Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)

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 Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83

Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)

Tacrolimus DRUG

Given IV then PO

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

Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with refractory B-cell or T-cell non-Hodgkin's lymphoma or Hodgkin's lymphoma who are eligible for allogeneic transplantation
• An 8/8 human leukocyte antigen (HLA) matched (high resolution typing at A, B, C, DRB1) sibling or unrelated donor
• Left ventricular ejection fraction (EF) \>= 45%
• Forced expiratory volume in one second (FEV1) \>= 50%
• Forced vital capacity (FVC) \>= 50%
• Diffusing capacity of the lung for carbon monoxide (DLCO) \>= 50%
• Estimated serum creatinine clearance \>= 50 ml/min (using the Cockcroft-Gault formula)
• Serum creatinine =\< 1.6 mg/dL
• Serum bilirubin =\< 2 x upper limit of normal
• Serum glutamate pyruvate transaminase (SGPT) =\< 2 x upper limit of normal
• Voluntary signed Institutional Review Board (IRB)-approved informed consent before performance of 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
• Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study; female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study; male subject agrees to use an acceptable method for contraception for the duration of the study

You may not qualify if:

• Patient with active central nervous system (CNS) disease
• Pregnancy (positive beta human chorionic gonadotropin \[HCG\] test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization) or currently breast-feeding; pregnancy testing is not required for post-menopausal or surgically sterilized women
• Active hepatitis B, either active carrier (hepatitis B virus surface antigen \[HBsAg\] +) or viremic (hepatitis B virus \[HBV\] deoxyribonucleic acid \[DNA\] \>= 10,000 copies/mL, or \>= 2,000 IU/mL)
• Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology
• Human immunodeficiency virus (HIV) infection
• Active uncontrolled bacterial, viral or fungal infections
• Exposure to other investigational drugs within 2 weeks before enrollment
• Grade \>= 3 non-hematologic toxicity from previous therapy that has not resolved to =\< grade 1
• Radiation therapy to head and neck (excluding eyes), and internal organs of chest, abdomen or pelvis in the month prior to enrollment
• Prior whole brain irradiation
• Prior autologous stem-cell transplant (SCT) in the prior 3 months

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

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lymphoma, B-Cell; Hodgkin Disease; Lymphoma, T-Cell

Interventions

Antilymphocyte Serum; thymoglobulin; Busulfan; Clofarabine; Gemcitabine; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; Rituximab; CT-P10; Tacrolimus

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Macrolides; Lactones

Results Point of Contact

• Title: Dr. Yago Nieto, MD, PhD/ Stem Cell Transplantation Department
• Organization: University of Texas MD Anderson Cancer Center

ynieto@mdanderson.org

713-792-8750

Study Officials

• Yago L Nieto, MD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: October 3, 2012
• First Posted: October 5, 2012
• Study Start: October 25, 2012
• Primary Completion: June 5, 2024
• Study Completion: June 5, 2024
• Last Updated: February 28, 2025
• Results First Posted: February 28, 2025

Record last verified: 2025-02

Locations

US (1)