Carmustine, Etoposide, Cytarabine, Melphalan, and Alemtuzumab Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

• ClinicalTrials.gov Identifier: NCT00908180
• Recruitment Status: Unknown
• First Posted: May 25, 2009
• Last Update Posted: August 2, 2013
• Sponsor: Cancer Research UK
• Information provided by: National Cancer Institute (NCI)

Study Description

Brief Summary:

RATIONALE: Giving chemotherapy before a donor 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. Monoclonal antibodies, such as alemtuzumab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine before and after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.

PURPOSE: This phase II trial is studying the side effects of giving carmustine together with etoposide, cytarabine, melphalan, and alemtuzumab followed by donor stem cell transplant and to see how well it works in treating patients with relapsed or refractory Hodgkin lymphoma.

Condition or disease	Intervention/treatment	Phase
Lymphoma	Biological: alemtuzumab; Biological: donor lymphocytes; Drug: carmustine; Drug: cyclosporine; Drug: cytarabine; Drug: etoposide; Drug: melphalan; Procedure: allogeneic hematopoietic stem cell transplantation	Phase 2

Detailed Description:

OBJECTIVES:

• To document the toxicity and feasibility of reduced-intensity conditioning regimen comprising carmustine, etoposide, cytarabine, melphalan, and alemtuzumab followed by allogeneic hematopoietic stem cell transplantation in patients with primary refractory or relapsed Hodgkin lymphoma.
• To document the survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Conditioning regimen: Patients receive BEAM chemotherapy comprising carmustine IV over 2 hours on day -6, etoposide IV over ≥ 1 hour on days -5 to -2, cytarabine IV over 15 minutes twice daily on days -5 to -2, and melphalan IV on day -1. Patients also receive alemtuzumab IV on days -5 to -1.
• Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT on day 0.
• Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV (or orally once tolerable) beginning on day -1 and continuing until day 60, followed by a taper in the absence of GVHD.
• Donor lymphocyte infusion (DLI): Patients with mixed chimerism or stable residual disease at 6 months after HSCT or disease progression or relapse at any time after HSCT may receive DLI in the absence of GVHD.

After completion of study treatment, patients are followed periodically for 3 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 47 participants
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Reduced Intensity Allogeneic Transplantation for Refractory Hodgkin Lymphoma
• Study Start Date: July 2009
• Estimated Primary Completion Date: July 2014

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Progression-free survival at 3 years

Secondary Outcome Measures :

1. Donor engraftment rates, including chimerism at 3 and 6 months
2. Non-relapse mortality at 100 days, 1 year, and 2 years post-transplant
3. Incidence of grade II-IV toxicity as assessed by NCI CTCAE v3.0
4. Incidence, severity, and timing of acute and chronic graft-versus-host disease
5. Response rates
6. Relapse rates
7. Response to donor lymphocyte infusions
8. Overall survival

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

DISEASE CHARACTERISTICS:

• Confirmed diagnosis of Hodgkin lymphoma, meeting 1 of the following criteria:

  • Refractory to initial multi-agent induction therapy and achieved less than a complete response to one line of salvage chemotherapy
  • In first relapse and achieved less than a partial response to one line of salvage chemotherapy
• No progressive disease
• Must have an HLA-matched (≥ 9/10) sibling or unrelated donor available

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Creatinine clearance ≥ 50 mL/min
• Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2 times ULN
• LVEF ≥ 40%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2-3 months after completion of study treatment
• No HIV positivity
• No other malignancy within the past 5 years, except for nonmelanoma skin cancer or stage 0 (in situ) cervical carcinoma
• No concurrent serious medical condition that would preclude an allograft
• No symptomatic respiratory compromise

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior high-dose therapy or allograft

Contacts and Locations

Sponsors and Collaborators

Cancer Research UK

Investigators

• Principal Investigator: Karl Peggs, MD; University College London (UCL) Cancer Institute

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Das-Gupta E, Thomson KJ, Bloor AJC, Clark AD, Mackinnon S, Kayani I, Clifton-Hadley L, Patrick P, El-Mehidi N, Lawrie A, Kirkwood AA, Russell NH, Linch DC, Peggs KS. Allo-HSCT in transplant-naïve patients with Hodgkin lymphoma: a single-arm, multicenter study. Blood Adv. 2019 Dec 23;3(24):4264-4270. doi: 10.1182/bloodadvances.2019001016.

• ClinicalTrials.gov Identifier: NCT00908180
• Other Study ID Numbers: CRUK-PAIReD; CDR0000640493 ( Registry Identifier: PDQ (Physician Data Query) ); EUDRACT-2008-004956-60; EU-20930; UCL/08/0121
• First Posted: May 25, 2009
• Last Update Posted: August 2, 2013
• Last Verified: June 2009

Keywords provided by National Cancer Institute (NCI):

recurrent adult Hodgkin lymphoma

Additional relevant MeSH terms:

Lymphoma; Hodgkin Disease; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Cytarabine; Cyclosporine; Etoposide; Melphalan; Alemtuzumab; Carmustine; Cyclosporins; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Anti-Infective Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antifungal Agents; Dermatologic Agents