search
Back to results

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

Primary Purpose

Hematopoietic Cell Transplantation Recipient, Refractory B-Cell Non-Hodgkin Lymphoma, Refractory Hodgkin Lymphoma

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Bone Marrow Transplantation
Allogeneic Hematopoietic Stem Cell Transplantation
Anti-Thymocyte Globulin
Busulfan
Clofarabine
Gemcitabine Hydrochloride
Mycophenolate Mofetil
Peripheral Blood Stem Cell Transplantation
Pharmacological Study
Rituximab
Tacrolimus
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematopoietic Cell Transplantation Recipient

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care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

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm Description

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.

Outcomes

Primary Outcome Measures

Optimal dose of gemcitabine hydrochloride determined by dose limiting toxicity (Phase I)
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)
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)
Overall survival (Phase II)
Response rate (Phase II)
Complete response rate (Phase II)
Incidence of grade 2-4 and grade 3-4 acute GVHD (Phase II)
Incidence of limited and extensive chronic GVHD (Phase II)

Secondary Outcome Measures

Full Information

First Posted
October 3, 2012
Last Updated
August 9, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT01701986
Brief Title
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
Gemcitabine/Clofarabine/Busulfan and Allogeneic Transplantation for Aggressive Lymphomas
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 25, 2012 (Actual)
Primary Completion Date
May 31, 2024 (Anticipated)
Study Completion Date
May 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematopoietic Cell Transplantation Recipient, Refractory B-Cell Non-Hodgkin Lymphoma, Refractory Hodgkin Lymphoma, Refractory T-Cell Non-Hodgkin Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic Bone Marrow Transplantation
Other Intervention Name(s)
Allo BMT, Allogeneic BMT
Intervention Description
Undergo allogeneic BMT
Intervention Type
Procedure
Intervention Name(s)
Allogeneic Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT
Intervention Description
Undergo allogeneic BMT or PBSCT
Intervention Type
Biological
Intervention Name(s)
Anti-Thymocyte Globulin
Other Intervention Name(s)
Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Clofarabine
Other Intervention Name(s)
Clofarex, Clolar
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Gemcitabine Hydrochloride
Other Intervention Name(s)
dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011, LY188011
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
Cellcept, MMF
Intervention Description
Given IV then PO
Intervention Type
Procedure
Intervention Name(s)
Peripheral Blood Stem Cell Transplantation
Other Intervention Name(s)
PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation
Intervention Description
Undergo allogeneic PBSCT
Intervention Type
Other
Intervention Name(s)
Pharmacological Study
Intervention Description
Correlative studies
Intervention Type
Biological
Intervention Name(s)
Rituximab
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
FK 506, Fujimycin, Hecoria, Prograf, Protopic
Intervention Description
Given IV then PO
Primary Outcome Measure Information:
Title
Optimal dose of gemcitabine hydrochloride determined by dose limiting toxicity (Phase I)
Description
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.
Time Frame
Within 30 days of transplant
Title
Success rate (Phase II)
Description
Defined as percentage of patients who are alive, engrafted and without grade 3-4 graft versus host disease (GVHD).
Time Frame
Up to 100 days post-transplant
Title
Rate of event-free survival (Phase II)
Time Frame
Up to 5 years
Title
Overall survival (Phase II)
Time Frame
Up to 5 years
Title
Response rate (Phase II)
Time Frame
Up to 5 years
Title
Complete response rate (Phase II)
Time Frame
Up to 5 years
Title
Incidence of grade 2-4 and grade 3-4 acute GVHD (Phase II)
Time Frame
Up to 5 years
Title
Incidence of limited and extensive chronic GVHD (Phase II)
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yago L Nieto, MD,PHD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
University of Texas MD Anderson Cancer Center Website

Learn more about this trial

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

We'll reach out to this number within 24 hrs