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 |
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Recruitment Status :
Active, not recruiting
First Posted : October 5, 2012
Last Update Posted : February 27, 2023
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| 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 |
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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 80 participants |
| Allocation: | N/A |
| 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 : | May 31, 2024 |
| Estimated Study Completion Date : | May 31, 2024 |
| Arm | Intervention/treatment |
|---|---|
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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:
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation Undergo allogeneic BMT or PBSCT
Other Names:
Biological: Anti-Thymocyte Globulin Given IV
Other Names:
Drug: Busulfan Given IV
Other Names:
Drug: Clofarabine Given IV
Other Names:
Drug: Gemcitabine Hydrochloride Given IV
Other Names:
Drug: Mycophenolate Mofetil Given IV then PO
Other Names:
Procedure: Peripheral Blood Stem Cell Transplantation Undergo allogeneic PBSCT
Other Names:
Other: Pharmacological Study Correlative studies Biological: Rituximab Given IV
Other Names:
Drug: Tacrolimus Given IV then PO
Other Names:
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- 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 ]
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.
| Ages Eligible for Study: | 12 Years to 65 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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
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
| United States, Texas | |
| M D Anderson Cancer Center | |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: | Yago L Nieto, MD,PHD | M.D. Anderson Cancer Center |
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01701986 |
| 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: | February 27, 2023 |
| Last Verified: | February 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Lymphoma Lymphoma, Non-Hodgkin Hodgkin Disease Lymphoma, B-Cell Lymphoma, T-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Gemcitabine Mycophenolic Acid Rituximab Antineoplastic Agents, Immunological |
Busulfan Clofarabine Antibodies Immunoglobulins Antibodies, Monoclonal Tacrolimus Thymoglobulin Antilymphocyte Serum Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents Antirheumatic Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action |