Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00003770

Trial Description

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Title

Treatment Protocol for Relapsed Anaplastic Large Cell Lymphoma of Childhood and Adolescence

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

RATIONALE: Giving combination chemotherapy and total-body irradiation before a peripheral
stem cell transplant that uses the patient's or a donor's stem cells, helps stop both the
growth of cancer cells and the patient's immune system from rejecting the stem cells. When
the stem cells are infused into the patient they may help the patient's bone marrow make
stem cells, red blood cells, white blood cells, and platelets. Giving combination
chemotherapy and total-body irradiation followed by a stem cell transplant may be an
effective treatment for anaplastic large cell lymphoma.

PURPOSE: This clinical trial is studying how well combination chemotherapy followed by stem
cell transplant works in treating young patients with progressive or relapsed anaplastic
large cell lymphoma.

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Brief Summary in Scientific Language

OBJECTIVES:

Primary

- Improve the probability of event-free survival in children and adolescents with early
progression of anaplastic large cell lymphoma (ALCL) and/or relapse of ALCL with
CD3-positive immunophenotype treated with reinduction combination chemotherapy followed
by allogeneic or autologous stem cell transplantation.

- Determine whether a conditioning regimen comprising carmustine, etoposide phosphate,
cytarabine, and melphalan (BEAM) (without total body irradiation) for autologous stem
cell transplantation is an effective treatment for patients with relapsed CD3-negative
ALCL occurring after the intensive phase of treatment.

- Determine the impact of vinblastine in patients with late relapse of CD3-negative ALCL
who have not received vinblastine during frontline therapy.

Secondary

- Determine overall survival and treatment-related mortality in patients treated with
these regimens.

- Determine acute and long-term toxicity in patients treated with these regimens.

- Determine the rate of acute and chronic graft-vs-host disease in patients treated with
allogeneic stem cell transplantation.

OUTLINE: This is a multicenter, prospective, nonrandomized study. Patients are stratified
according to time from initial diagnosis to progression/relapse, immunophenotype of lymphoma
cells (CD3-positive + vs CD3-negative), stem cell donor availability (matched sibling donor
vs 9/10 or 10/10 matched unrelated donor), and vinblastine during frontline therapy (yes vs
no).

- Group 1 (early progression): Patients receive 1 course of ICM chemotherapy followed by
1 course of ICI chemotherapy.

- ICM chemotherapy: Patients receive methotrexate, cytarabine, and prednisolone
intrathecally (IT) on day 1, mitoxantrone hydrochloride IV over 5 hours on days 1
and 2, carboplatin IV continuously on days 2-5 and ifosfamide IV continuously on
days 2-6.

- ICI chemotherapy: Patients receive methotrexate, cytarabine, and prednisolone
intrathecally on day 1, idarubicin IV over 4 hours on days 1 and 2, carboplatin IV
continuously on days 2-5, and ifosfamide IV continuously on days 2-6.

Patients then proceed to allogeneic stem cell transplantation.

- Group 2 (relapsed disease and CD3-positive lymphoma cells): Patients are stratified
according to stem cell donor availability (yes vs no).

- Available donor: Patients receive 2 courses of CC chemotherapy and then proceed to
allogeneic stem cell transplantation.

- Unavailable donor : Patients receive 2 courses of CC chemotherapy comprising
dexamethasone orally or IV on days 1-5, vindesine IV on day 1, cytarabine IV over
3 hours on days 1 and 2, etoposide phosphate IV over 2 hours on days 3-5, and
methotrexate, cytarabine, and prednisolone IT on day 5. Patients then receive 1
course of CVA chemotherapy comprising oral lomustine on day 1, vinblastine IV on
days 1, 8, 15, and 22, and cytarabine IV over 1 hour on days 1-5. Patients undergo
leukapheresis for collection of autologous peripheral blood stem cells after the
first and/or second course of CC chemotherapy. Patients then proceed to autologous
stem cell transplantation.

- Group 3 (relapsed disease, CD3-negative immunophenotype, and received vinblastine
during frontline therapy): Patients receive 2 courses of CC chemotherapy and 1 course
of CVA chemotherapy as described above. Patients undergo leukapheresis for collection
of autologous peripheral blood stem cells (PBSC) after the first and/or second course
of CC chemotherapy. Patients then proceed to autologous stem cell transplantation.

- Group 4 (late relapse, CD3-negative immunophenotype, and did not receive vinblastine
during frontline therapy): Patients receive vinblastine IV once weekly for 24 months.
Patients with disease progression during or relapsed disease after vinblastine therapy
undergo treatment as in group 3.

- Autologous stem cell transplantation (SCT): Patients receive a conditioning regimen
comprising carmustine IV over 1 hour on day -7, etoposide phosphate IV over 1 hour and
cytarabine IV over 30 minutes on days -6 to -3, and melphalan IV over 15 minutes on day
-2. Patients undergo autologous SCT on day 0.

- Allogeneic SCT: Beginning 4-6 weeks after the start of the last chemotherapy course,
patients receive 1 of the following conditioning regimens based on age:

- Patients > 2 years of age undergo total body irradiation on days -7 to -5 and
receive thiotepa IV over 1 hour on day -4 and etoposide IV over 4 hours on day -3.
Patients undergo allogeneic SCT on day 0.

- Patients ≤ 2 years of age receive oral busulfan 4 times daily on days -8 to -5,
thiotepa IV over 1 hour twice on day -4, and etoposide phosphate IV over 4 hours
on day -3. Patients undergo allogeneic SCT on day 0.

Patients undergoing SCT from an unrelated donor also receive antithymocyte globulin IV over
4 hours on days -3 to -1.

All patients receive graft-versus-host (GVHD) prophylaxis as described below.

- GVHD prophylaxis: GVHD prophylaxis is administered as per donor status.

- Matched sibling donor: Patients receive cyclosporine IV over 2 hours or orally on
day -1 to 60 followed by a taper.

- 10/10 or 9/10 matched unrelated donor: Patients receive cyclosporine IV over 2
hours or orally on days -1 to 100 followed by a taper, methotrexate IV on days 1,
3, and 6, and leucovorin calcium IV on days 2, 4, and 7.

- Mismatched donor: Patients do not receive GVHD prophylaxis, however, CD3-positive
lymphocytes are extracted from donor stem cells.

After completion of study treatment, patients are followed periodically for 10 years.

PROJECTED ACCRUAL: A total of 96 patients will be accrued for this study.

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Organizational Data

  •   DRKS00003770
  •   2012/11/16
  •   2006/04/19
  •   yes
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Secondary IDs

  •   2005-003321-57 
  •   NCT00317408  (ClinicalTrials.gov)
  •   CDR0000466639  (European Inter-Group Co-operation on Childhood Non-Hodgkin Lymphoma)
  •   EICNHL-ALCL-RELAPSE 
  •   AIEOP-EICNHL-ALCL-RELAPSE 
  •   BFM-EICNHL-ALCL-RELAPSE 
  •   BSPHO-EICNHL-ALCL-RELAPSE 
  •   DCOG-EICNHL-ALCL-RELAPSE 
  •   NOPHO-EICNHL-ALCL-RELAPSE 
  •   PPLLSG-EICNHL-ALCL-RELAPSE 
  •   SFCE-EICNHL-ALCL-RELAPSE 
  •   SHOP-EICNHL-ALCL-RELAPSE 
  •   CCLG-NHL-2006-01 
  •   EU-205118 
  •   EU-20618 
  •   EUDRACT-2005-003321-57 
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Health Condition or Problem studied

  •   Lymphoma
  •   C84.6 -  Anaplastic large cell lymphoma, ALK-positive
  •   C84.7 -  Anaplastic large cell lymphoma, ALK-negative
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Interventions/Observational Groups

  •   Biological: anti-thymocyte globulin
  •   Drug: busulfan
  •   Drug: carboplatin
  •   Drug: carmustine
  •   Drug: cyclosporine
  •   Drug: cytarabine
  •   Drug: dexamethasone
  •   Drug: etoposide phosphate
  •   Drug: idarubicin
  •   Drug: ifosfamide
  •   Drug: leucovorin calcium
  •   Drug: lomustine
  •   Drug: melphalan
  •   Drug: methotrexate
  •   Drug: mitoxantrone hydrochloride
  •   Drug: prednisolone
  •   Drug: thiotepa
  •   Drug: vinblastine sulfate
  •   Drug: vindesine
  •   Procedure: allogeneic hematopoietic stem cell transplantation
  •   Procedure: autologous hematopoietic stem cell transplantation
  •   Procedure: peripheral blood stem cell transplantation
  •   Radiation: total-body irradiation
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Characteristics

  •   Interventional
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  •   Non-randomized controlled trial
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  •   Treatment
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  •   N/A
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Primary Outcome

- Event-free survival as measured by the Kaplan-Meier method

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Secondary Outcome

- Proportion of patients who are treated on protocol among all patients who meet the inclusion criteria
- Overall survival
- Acute and long term toxicity
- Rate of acute and chronic graft-vs-host disease in patients with allogeneic stem cell transplantation
- Treatment related mortality

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Countries of Recruitment

  •   Austria
  •   Belgium
  •   Czech Republic
  •   France
  •   Germany
  •   Ireland
  •   Italy
  •   Netherlands
  •   Poland
  •   Sweden
  •   Switzerland
  •   United Kingdom
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Locations of Recruitment

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Recruitment

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  •   2004/04/30
  •   96
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   no minimum age
  •   21   Years
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Additional Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed anaplastic large cell lymphoma (ALCL)

- Progressive disease OR first relapse

- No second or subsequent relapse of ALCL

- Slides available for national central pathology review

- Availability of 1 of the following (for allogeneic stem cell transplantation only):

- HLA-identical matched sibling donor

- 10/10 HLA-matched nonsibling donor (related or unrelated)

- 9/10 HLA-matched nonsibling donor (1-antigen-mismatched related or unrelated
donor)

- < 9/10 HLA-mismatched donor (related or unrelated)

- Stem cells may be obtained from unmanipulated bone marrow or peripheral
blood stem cells after filgrastim (G-CSF) stimulation

PATIENT CHARACTERISTICS:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Adequate hepatic, renal, and cardiac function

- No HIV infection or AIDS

- No severe immunodeficiency

- No other prior malignancy

- No pre-existing disease or condition prohibiting study treatment

PRIOR CONCURRENT THERAPY:

- At least 2 months since prior chemotherapy or radiotherapy

- No significant pretreatment for first relapse

- No prior organ transplantation

- No concurrent participation in another clinical trial

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Exclusion Criteria

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Addresses

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    • European Inter-Group Co-operation on Childhood Non-Hodgkin Lymphoma
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    • Kinderklinik
    • Alfred Reiter, MD 
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    • Kinderklinik
    • Alfred Reiter, MD 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting complete, follow-up continuing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   112
  •   2015/10/01
* This entry means the parameter is not applicable or has not been set.