Clinical Trial: NCT03136146 - My Cancer Genome

NCT03136146

Description:

This phase II trial studies the side effects and how well combination chemotherapy works in treating patients with acute lymphoblastic leukemia, lymphoblastic lymphoma, Burkitt lymphoma/leukemia, or double-hit lymphoma/leukemia that has come back or does not respond to treatment. Drugs used in chemotherapy, such as clofarabine, etoposide, cyclophosphamide, vincristine sulfate liposome, dexamethasone and bortezomib, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Related Conditions:

Acute Lymphoblastic Leukemia
Burkitt Leukemia
Burkitt Lymphoma
Diffuse Large B-Cell Lymphoma
Double-Hit Lymphoma

Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT03136146

Trial Eligibility

Document

Title

Brief Title: Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma, Burkitt Lymphoma/Leukemia, or Double-Hit Lymphoma/Leukemia
Official Title: Lead-In and Phase II Study of Clofarabine, Etoposide, Cyclophosphamide [CEC], Liposomal Vincristine (VCR), Dexamethasone and Bortezomib in Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LL)

Clinical Trial IDs

ORG STUDY ID: 2016-0211
SECONDARY ID: NCI-2018-01198
SECONDARY ID: 2016-0211
SECONDARY ID: P30CA016672
NCT ID: NCT03136146

Conditions

Burkitt Leukemia
High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
Recurrent Acute Lymphoblastic Leukemia
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Burkitt Leukemia
Recurrent Burkitt Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
Refractory Acute Lymphoblastic Leukemia
Refractory Burkitt Leukemia
Refractory Burkitt Lymphoma
Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
Refractory Lymphoblastic Lymphoma

Interventions

Drug	Synonyms	Arms
Bortezomib	[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade	Treatment (combination chemotherapy)
Clofarabine	Clofarex, Clolar	Treatment (combination chemotherapy)
Cyclophosphamide	(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719	Treatment (combination chemotherapy)
Dexamethasone	Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex	Treatment (combination chemotherapy)
Etoposide	Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16	Treatment (combination chemotherapy)
Ofatumumab	Arzerra, GSK1841157, HuMax-CD20, HuMax-CD20, 2F2	Treatment (combination chemotherapy)
Pegfilgrastim	Filgrastim SD-01, filgrastim-SD/01, Fulphila, HSP-130, Jinyouli, Neulasta, Neulastim, Pegfilgrastim Biosimilar HSP-130, Pegfilgrastim Biosimilar Pegcyte, SD-01, SD-01 sustained duration G-CSF	Treatment (combination chemotherapy)
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, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima	Treatment (combination chemotherapy)
Vincristine Sulfate Liposome	Marqibo	Treatment (combination chemotherapy)

Purpose

Detailed Description

      PRIMARY OBJECTIVES:

      I. To collect the safety/toxicity information and assess the initial efficacy information
      (objective overall response rate: complete response [CR]+ CR with incomplete platelet
      recovery [CRp]/CR with incomplete bone marrow recovery [CRi]) after treatment with
      clofarabine, etoposide, cyclophosphamide (CEC), vincristine sulfate liposome (liposomal
      vincristine) (VCR), dexamethasone and bortezomib in relapsed/refractory acute lymphoblastic
      leukemia (ALL) or lymphoblastic lymphoma (LL) including relapsed/refractory Philadelphia (Ph)
      positive B-ALL/LL or Burkitt's leukemia/lymphoma or double-hit leukemia/lymphoma.

      SECONDARY OBJECTIVES:

      I. To determine the CR duration, event free survival (EFS), and overall survival (OS) after
      treatment with CEC, liposomal VCR, dexamethasone and bortezomib in relapsed/refractory ALL or
      LL including relapsed/refractory Ph positive B-ALL/LL or Burkitt's leukemia/lymphoma or
      double-hit leukemia/lymphoma.

      OUTLINE:

      INDUCTION: Patients receive clofarabine intravenously (IV) over 1-2 hours on days 1-5,
      etoposide IV over 2 hours on days 1-5, cyclophosphamide IV over 1 hour on days 1-5,
      vincristine sulfate liposome IV over 1 hour on days 2 and 11, dexamethasone orally (PO) daily
      or IV over 15 minutes on days 1-5, bortezomib subcutaneously (SC) on days 1, 4, 8 and 11,
      ofatumumab or rituximab IV over 4-24 hours on days 2 and 11, and pegfilgrastim SC on day 6 in
      the absence of disease progression or unacceptable toxicity. Patients may receive 1
      additional course of induction therapy depending on the disease response.

      CONSOLIDATION THERAPY: Patients receive clofarabine IV over 1-2 hours on days 1-4, etoposide
      IV over 2 hours on days 1-4, cyclophosphamide IV over 1 hour on days 1-4, vincristine sulfate
      liposome IV over 1 hour on days 2 and 11, dexamethasone PO or IV over 15 minutes on days 1-5,
      bortezomib SC on days 1, 4, 8 and 11, pegfilgrastim SC on day 6. Treatment repeats every 28
      days for up to 5 courses in the absence of disease progression or unacceptable toxicity.
      Patients may receive ofatumumab or rituximab IV over 4-24 hours on days 2 and 11 for 4
      courses.

Trial Arms

Name	Type	Description	Interventions
Treatment (combination chemotherapy)	Experimental	See detailed description	Bortezomib Clofarabine Cyclophosphamide Dexamethasone Etoposide Ofatumumab Pegfilgrastim Rituximab Vincristine Sulfate Liposome

Eligibility Criteria

        Inclusion Criteria:

          -  Relapsed and/or refractory Philadelphia negative acute lymphoblastic leukemia or
             lymphoblastic lymphoma (Lead-in and Phase 2)

          -  Relapsed and/or refractory Philadelphia positive acute lymphoblastic leukemia, Burkitt
             leukemia/lymphoma or "double-hit" leukemia/lymphoma (2 separate cohorts, phase II
             only)

          -  At least 21 days elapsed from prior systemic chemotherapy (at least 14 days elapsed
             from prior systemic chemotherapy in the setting of rapidly progressive disease without
             significant residual extramedullary toxicity). Hydroxyurea and dexamethasone permitted
             up to approximately 24 hours prior to the start of therapy. Interruption of tyrosine
             kinase inhibitor (TKI) not required in Ph positive ALL subset

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 3 (There may be
             certain patients with performance status [PS] 3 in the context of rapidly
             proliferative/refractory ALL who would benefit from this regimen. We don't want to
             exclude such patients who may derive benefit from this salvage regimen)

          -  Serum bilirubin =< 1.5 mg/dL

          -  Serum glutamate pyruvate transaminase (SGPT) =< 3 x upper limit normal (ULN), with
             exception for Gilbert's syndrome

          -  Estimated creatinine clearance or GFR (glomerular filtration rate) >= 50 mL/min

          -  Signed informed consent

        Exclusion Criteria:

          -  Active >= grade 3 peripheral neuropathy

          -  Active hepatic graft-versus-host disease

          -  Known positivity for hepatitis B or C

          -  Pregnancy

          -  Breast feeding after pregnant

Maximum Eligible Age:	N/A
Minimum Eligible Age:	N/A
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Incidence of adverse events
Time Frame:	Up to 8 years
Safety Issue:
Description:	The severity of the toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events.

Secondary Outcome Measures

Measure:	Overall survival
Time Frame:	From initiation of treatment, assessed up to 8 years
Safety Issue:
Description:	Will be estimated using the method of Kaplan and Meier. The log-rank tests will be used to compare the time-to-event outcomes among subgroups of patients.

Measure:	Event free survival
Time Frame:	From the treatment start, assessed up to 8 years
Safety Issue:
Description:	Will be estimated using the method of Kaplan and Meier. The log-rank tests will be used to compare the time-to-event outcomes among subgroups of patients.

Details

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

Last Updated

June 22, 2020

Clinical Trials /

Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma, Burkitt Lymphoma/Leukemia, or Double-Hit Lymphoma/Leukemia