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

Refractory B-Cell Non-Hodgkin Lymphoma Clinical Trial

Official title:

Gemcitabine/Clofarabine/Busulfan and Allogeneic Transplantation for Aggressive Lymphomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01701986
• Other study ID #: 2012-0506
• Secondary ID: NCI-2012-0205520
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 25, 2012
• Est. completion date: June 5, 2024

Study information

• Verified date: June 2024
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: June 5, 2024
• Est. primary completion date: June 5, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hematopoietic Cell Transplantation Recipient
• Hodgkin Disease
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Lymphoma, T-Cell
• Refractory B-Cell Non-Hodgkin Lymphoma
• Refractory Hodgkin Lymphoma
• Refractory T-Cell Non-Hodgkin Lymphoma

Intervention

Procedure:
• Allogeneic Bone Marrow Transplantation
Undergo allogeneic BMT
• Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic BMT or PBSCT

Biological:
• Anti-Thymocyte Globulin
Given IV

Drug:
• Busulfan
Given IV
• Clofarabine
Given IV
• Gemcitabine Hydrochloride
Given IV
• Mycophenolate Mofetil
Given IV then PO

Procedure:
• Peripheral Blood Stem Cell Transplantation
Undergo allogeneic PBSCT

Other:
• Pharmacological Study
Correlative studies

Biological:
• Rituximab
Given IV

Drug:
• Tacrolimus
Given IV then PO

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Within 30 days of transplant
Primary	Success rate (Phase II)	Defined as percentage of patients who are alive, engrafted and without grade 3-4 graft versus host disease (GVHD).	Up to 100 days post-transplant
Primary	Rate of event-free survival (Phase II)		Up to 5 years
Primary	Overall survival (Phase II)		Up to 5 years
Primary	Response rate (Phase II)		Up to 5 years
Primary	Complete response rate (Phase II)		Up to 5 years
Primary	Incidence of grade 2-4 and grade 3-4 acute GVHD (Phase II)		Up to 5 years
Primary	Incidence of limited and extensive chronic GVHD (Phase II)		Up to 5 years

External Links

•   University of Texas MD Anderson Cancer Center Website