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Trial record 57 of 101 for:    Behaviors and Mental Disorders[CONDITION-BROWSE-BRANCH] | Recruiting, Not yet recruiting, Available Studies | ( Map: Texas, United States ) | NIH, U.S. Fed

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

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ClinicalTrials.gov Identifier: NCT01701986
Recruitment Status : Recruiting
First Posted : October 5, 2012
Last Update Posted : May 29, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
Hematopoietic Cell Transplantation Recipient Refractory B-Cell Non-Hodgkin Lymphoma Refractory Hodgkin Lymphoma Refractory T-Cell Non-Hodgkin Lymphoma 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 Phase 1 Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To define the maximum tolerated dose (MTD) of infusional gemcitabine (gemcitabine hydrochloride) combined with fixed doses of clofarabine and busulfan in patients with lymphoma receiving an allogeneic stem-cell transplant (alloSCT).

II. To estimate the day +100 success rate, defined as percentage of patients who are alive, engrafted and without grade 3-4 graft-versus (vs.)-host-disease (GVHD).

SECONDARY OBJECTIVES:

I. To estimate the day +100 success rate (defined as percentage of patients who are alive, engrafted and without grade 3-4 graft-vs.-host-disease [GVHD]).

II. To estimate the rate of event-free (EFS). III. To estimate the rate of overall survival (OS). IV. To estimate the response rate (RR) (defined as # of responses / # of patients with measurable tumors).

V. To estimate the complete response (CR) rate (defined as # of complete responses / # of patients with measurable tumors).

VI. To estimate the incidence of grade 2-4 and grade 3-4 acute GVHD. VII. To estimate the incidence of limited and extensive chronic GVHD.

OUTLINE: This is a phase I, dose-escalation study of gemcitabine hydrochloride followed by a phase II study.

PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride intravenously (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 cluster of differentiation (CD)20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.

TRANSPLANT: Patients undergo allogeneic bone marrow (BMT) or peripheral blood stem cell transplant (PBSCT) on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or orally (PO). Beginning on day 0, patients receive mycophenolate mofetil IV over 2 hours or PO thrice daily (TID).

After completion of study treatment, patients are followed up at 3, 6, and 12 months, and then every 6 months for 4 years.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Gemcitabine/Clofarabine/Busulfan and Allogeneic Transplantation for Aggressive Lymphomas
Actual Study Start Date : October 25, 2012
Estimated Primary Completion Date : October 25, 2019
Estimated Study Completion Date : October 25, 2020


Arm Intervention/treatment
Experimental: Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)

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
Undergo allogeneic BMT
Other Names:
  • Allo BMT
  • Allogeneic BMT

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic BMT or PBSCT
Other Names:
  • Allogeneic Hematopoietic Cell Transplantation
  • Allogeneic Stem Cell Transplantation
  • HSC
  • HSCT

Biological: Anti-Thymocyte Globulin
Given IV
Other Names:
  • Antithymocyte Globulin
  • Antithymocyte Serum
  • ATG
  • ATGAM
  • ATS
  • Thymoglobulin

Drug: Busulfan
Given IV
Other Names:
  • 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

Drug: Clofarabine
Given IV
Other Names:
  • Clofarex
  • Clolar

Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011

Drug: Mycophenolate Mofetil
Given IV then PO
Other Names:
  • Cellcept
  • MMF

Procedure: Peripheral Blood Stem Cell Transplantation
Undergo allogeneic PBSCT
Other Names:
  • PBPC transplantation
  • PBSCT
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplant
  • Peripheral Stem Cell Transplantation

Other: Pharmacological Study
Correlative studies

Biological: Rituximab
Given IV
Other Names:
  • 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

Drug: Tacrolimus
Given IV then PO
Other Names:
  • FK 506
  • Fujimycin
  • Hecoria
  • Prograf
  • Protopic




Primary Outcome Measures :
  1. Optimal dose of gemcitabine hydrochloride determined by dose limiting toxicity (Phase I) [ Time Frame: Within 30 days of transplant ]
    Defined as grade 3-4 mucositis lasting for more than 3 days at peak severity or grade 3-4 skin toxicity lasting for more than 3 days at peak severity. The Bayesian Time to Event Continual Reassessment Method will be applied to determine the optimal gemcitabine dose in phase I.

  2. Success rate (Phase II) [ Time Frame: Up to 100 days post-transplant ]
    Defined as percentage of patients who are alive, engrafted and without grade 3-4 graft versus host disease (GVHD).

  3. Rate of event-free survival (Phase II) [ Time Frame: Up to 5 years ]
  4. Overall survival (Phase II) [ Time Frame: Up to 5 years ]
  5. Response rate (Phase II) [ Time Frame: Up to 5 years ]
  6. Complete response rate (Phase II) [ Time Frame: Up to 5 years ]
  7. Incidence of grade 2-4 and grade 3-4 acute GVHD (Phase II) [ Time Frame: Up to 5 years ]
  8. Incidence of limited and extensive chronic GVHD (Phase II) [ Time Frame: Up to 5 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01701986


Contacts
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Contact: Yago Nieto, MD,PHD 713-792-2466 ynieto@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Yago L. Nieto, MD,PHD    713-792-8750      
Principal Investigator: Yago L. Nieto, MD,PHD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Yago L Nieto, MD,PHD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01701986     History of Changes
Other Study ID Numbers: 2012-0506
NCI-2012-02055 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2012-0506 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: October 5, 2012    Key Record Dates
Last Update Posted: May 29, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Hodgkin Disease
Lymphoma, T-Cell
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gemcitabine
Clofarabine
Tacrolimus
Mycophenolic Acid
Busulfan
Thymoglobulin
Antilymphocyte Serum
Rituximab
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors