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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 : January 15, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE October 3, 2012
First Posted Date  ICMJE October 5, 2012
Last Update Posted Date January 15, 2021
Actual Study Start Date  ICMJE October 25, 2012
Estimated Primary Completion Date May 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 7, 2019)
  • 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.
  • 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).
  • Rate of event-free survival (Phase II) [ Time Frame: Up to 5 years ]
  • Overall survival (Phase II) [ Time Frame: Up to 5 years ]
  • Response rate (Phase II) [ Time Frame: Up to 5 years ]
  • Complete response rate (Phase II) [ Time Frame: Up to 5 years ]
  • Incidence of grade 2-4 and grade 3-4 acute GVHD (Phase II) [ Time Frame: Up to 5 years ]
  • Incidence of limited and extensive chronic GVHD (Phase II) [ Time Frame: Up to 5 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 4, 2012)
Maximum Tolerated Dose (MTD) of Infusional Gemcitabine [ Time Frame: 30 Days ]
Dose limiting toxicity (DLT) 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, occurring within 30 days from transplant. Patient outcome time of occurrence of DLT or, if DLT has not yet occurred by day 30, outcome will be the patient's follow-up time without DLT.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: October 4, 2012)
Success Rate [ Time Frame: 100 Days ]
Success rate defined as percentage of patients who are alive, engrafted and without grade 3-4 graft-vs.-host-disease (GVHD), rate of event-free (EFS), overall survival (OS), response rate (RR), complete response (CR) rate, incidence of grade 2-4 and grade 3-4 acute GVHD, and incidence of limited and extensive chronic GVHD.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE Gemcitabine/Clofarabine/Busulfan and Allogeneic Transplantation for Aggressive Lymphomas
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hematopoietic Cell Transplantation Recipient
  • Refractory B-Cell Non-Hodgkin Lymphoma
  • Refractory Hodgkin Lymphoma
  • Refractory T-Cell Non-Hodgkin Lymphoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.

Interventions:
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 4, 2012)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2022
Estimated Primary Completion Date May 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Yago Nieto, MD,PHD 713-792-2466 ynieto@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01701986
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Yago L Nieto, MD,PHD M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP