Clinical Trial: NCT01701986 - My Cancer Genome

NCT01701986

Description:

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.

Related Conditions:

B-Cell Non-Hodgkin Lymphoma
Hodgkin Lymphoma
T-Cell Non-Hodgkin Lymphoma

Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT01701986

Trial Eligibility

Document

Title

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

Clinical Trial IDs

ORG STUDY ID: 2012-0506
SECONDARY ID: NCI-2012-02055
SECONDARY ID: 2012-0506
SECONDARY ID: P30CA016672
NCT ID: NCT01701986

Conditions

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

Interventions

Drug	Synonyms	Arms
Anti-Thymocyte Globulin	Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin	Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
Busulfan	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	Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
Clofarabine	Clofarex, Clolar	Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
Gemcitabine Hydrochloride	dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011, LY188011	Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
Mycophenolate Mofetil	Cellcept, MMF	Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
Rituximab	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	Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
Tacrolimus	FK 506, Fujimycin, Hecoria, Prograf, Protopic	Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)

Purpose

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.

Trial Arms

Name	Type	Description	Interventions
Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)	Experimental	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.	Anti-Thymocyte Globulin Busulfan Clofarabine Gemcitabine Hydrochloride Mycophenolate Mofetil Rituximab Tacrolimus

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

Maximum Eligible Age:	65 Years
Minimum Eligible Age:	12 Years
Eligible Gender:	All
Healthy Volunteers:	Accepts Healthy Volunteers

Primary Outcome Measures

Measure:	Optimal dose of gemcitabine hydrochloride determined by dose limiting toxicity (Phase I)
Time Frame:	Within 30 days of transplant
Safety Issue:
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.

Details

Phase:	Phase 1/Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	M.D. Anderson Cancer Center

Last Updated

January 15, 2021

Clinical Trials /

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