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

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ClinicalTrials.gov Identifier: NCT03136146
Recruitment Status : Recruiting
First Posted : May 2, 2017
Last Update Posted : June 5, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Drug: Bortezomib Drug: Clofarabine Drug: Cyclophosphamide Drug: Dexamethasone Drug: Etoposide Biological: Ofatumumab Biological: Pegfilgrastim Biological: Rituximab Drug: Vincristine Sulfate Liposome Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : August 9, 2017
Estimated Primary Completion Date : August 1, 2025
Estimated Study Completion Date : August 1, 2026


Arm Intervention/treatment
Experimental: Treatment (combination chemotherapy)
See detailed description
Drug: Bortezomib
Given SC
Other Names:
  • [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid
  • LDP 341
  • MLN341
  • PS-341
  • PS341
  • Velcade

Drug: Clofarabine
Given IV
Other Names:
  • Clofarex
  • Clolar

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-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

Drug: Dexamethasone
Given IV or PO
Other Names:
  • 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

Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16
  • VP 16-213
  • VP-16
  • VP-16-213
  • VP16

Biological: Ofatumumab
Given IV
Other Names:
  • Arzerra
  • GSK1841157
  • HuMax-CD20
  • HuMax-CD20, 2F2

Biological: Pegfilgrastim
Given SC
Other Names:
  • 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

Biological: Rituximab
Given IV
Other Names:
  • 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

Drug: Vincristine Sulfate Liposome
Given IV
Other Name: Marqibo




Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 8 years ]
    The severity of the toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events.

  2. Overall response rate (ORR) (Phase II) [ Time Frame: Up to 8 years ]
    Will be estimated along with the exact 95% confidence interval.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: From initiation of treatment, assessed up to 8 years ]
    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.

  2. Event free survival [ Time Frame: From the treatment start, assessed up to 8 years ]
    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.



Information from the National Library of Medicine

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.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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): NCT03136146


Contacts
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Contact: Maro Ohanian, DO 713-792-7305 mohanian@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Maro Ohanian    713-792-2631      
Principal Investigator: Maro Ohanian         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Maro Ohanian M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03136146     History of Changes
Other Study ID Numbers: 2016-0211
NCI-2018-01198 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-0211 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: May 2, 2017    Key Record Dates
Last Update Posted: June 5, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Burkitt Lymphoma
Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Dexamethasone
Dexamethasone acetate
Cyclophosphamide
Rituximab
Etoposide
Etoposide phosphate
Bortezomib
Vincristine
Clofarabine
Ofatumumab
Antineoplastic Agents, Immunological
BB 1101