Chemotherapy, Radiation Therapy, and Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer

• ClinicalTrials.gov Identifier: NCT00005092
• Recruitment Status: Completed
• First Posted: April 23, 2004
• Last Update Posted: October 26, 2018
• Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): M.D. Anderson Cancer Center

Tracking Information

• First Submitted Date: April 6, 2000
• First Posted Date: April 23, 2004
• Last Update Posted Date: October 26, 2018
• Actual Study Start Date: May 28, 1999
• Actual Primary Completion Date: August 28, 2002 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 25, 2010)

Maximum Tolerated Dose (MTD) of T-cells photochemically treated with psoralen and ultraviolet A [ Time Frame: 100 days ]

MTD defined as dose preceding that at which at least 2 of 3 patients experience dose limiting toxicities. Patients followed for 100 days.

• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Chemotherapy, Radiation Therapy, and Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer
• Official Title: A Phase I Study of Photochemically Treated Donor T-Cell Supplements in HLA Haplotype Mismatched Hematopoietic Stem Cell Transplantation

Brief Summary

RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by the chemotherapy or radiation therapy used to kill tumor cells. Sometimes the transplanted cells are rejected by the body's normal tissues. Transplanting donated cells that have been treated with psoralen may prevent this from happening.

PURPOSE: Phase I trial to study the effectiveness of chemotherapy, radiation therapy, and psoralen-treated donor cells in treating patients who are undergoing peripheral stem cell transplantation for hematologic cancer.

Detailed Description

OBJECTIVES: I. Determine the maximum tolerated dose of T-cells photochemically treated with psoralen and ultraviolet A given with peripheral stem cell transplantation in patients with hematologic malignancies or bone marrow failure myelodysplastic syndrome. II. Assess the toxicity of this treatment in these patients. III. Evaluate this regimen in terms of prevention of graft versus host disease and control of malignancy in these patients.

OUTLINE: This is a dose escalation, multicenter study of T-cells photochemically treated with psoralen and ultraviolet A. Patients receive thiotepa IV over 2 hours on day 1, cyclophosphamide IV over 2 hours on days 2 and 3, and whole body radiotherapy on days 5-8. Patients undergo preserved stem cell or bone marrow allogeneic transplant plus psoralen treated T-cell allogeneic transplant on day 9. Cohorts of 3-6 patients receive escalating doses of photochemically treated T-cells until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 patients experience dose limiting toxicities. Patients are followed for 100 days.

PROJECTED ACCRUAL: A maximum of 37 patients will be accrued for this study.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Leukemia
• Lymphoma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes

Intervention

• Drug: Cyclophosphamide
  IV over 2 hours on days 2 and 3
  Other Names:

  • Cytoxan
  • Neosar
• Drug: Psoralen
  Psoralen treated T-cell allogeneic transplant on day 9
  Other Names:

  • Methoxsalen
  • 8-methoxypsoralen
  • UVADEX
  • Oxsoralen-Ultra
  • Oxsoralen
  • 8-MOP
• Drug: Thiotepa
  IV over 2 hours on day 1
• Procedure: Allogeneic bone marrow transplantation
  Preserved stem cell or bone marrow allogeneic transplant plus psoralen treated T-cell allogeneic transplant on day 9
• Procedure: In vitro-treated peripheral blood stem cell transplantation (PBSCT)
  Preserved stem cell or bone marrow allogeneic transplant plus psoralen treated T-cell allogeneic transplant on day 9
  Other Name: PBSCT
• Radiation: Radiation Therapy (RT)
  Whole body radiotherapy on days 5-8.
  Other Name: Radiotherapy

Study Arms

Experimental: Chemo, RT + PSCT

Chemotherapy, Radiation Therapy, and Peripheral Stem Cell Transplantation

Interventions:

• Drug: Cyclophosphamide
• Drug: Psoralen
• Drug: Thiotepa
• Procedure: Allogeneic bone marrow transplantation
• Procedure: In vitro-treated peripheral blood stem cell transplantation (PBSCT)
• Radiation: Radiation Therapy (RT)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 25, 2010): 7
• Original Enrollment: Not Provided
• Actual Study Completion Date: August 28, 2002
• Actual Primary Completion Date: August 28, 2002 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS: Hematologic malignancy, including acute myeloid or lymphoid leukemia of any FAB subtype, not in remission with chemotherapy or requiring bone marrow transplant OR Chronic myeloid leukemia, advanced beyond first chronic phase OR Myelodysplasia, including secondary to prior chemotherapy, with: Granulocyte count less than 500/mm3 OR Platelet count less than 50,000/mm3 OR High risk cytogenetic abnormalities such as +8, -7, -5, or 11q23 OR Intermediate or high grade lymphoma without response to initial therapy or in relapse OR Multiple myeloma without response to initial therapy or in relapse OR Stage IV low grade lymphoma or chronic lymphocytic leukemia not achieving remission with 2 regimens No aplastic anemia Related haploidentical donor (1-3 HLA-A, B, and/or DR mismatch) for collection of stem cells and whole blood T-cells required

PATIENT CHARACTERISTICS: Age: 6 months to 49 years Performance status: ECOG 0-2 Life expectancy: Greater than 12 weeks Hematopoietic: See Disease Characteristics Hepatic: Bilirubin less than 1.5 mg/dL SGPT less than 3 times upper limit of normal Renal: Creatinine less than 1.5 mg/dL Cardiovascular: Left ventricular ejection fraction at least 45% No symptoms or active treatment of left ventricular failure Pulmonary: Corrected DLCO at least 50% Other: No acute viral, bacterial, or fungal infection No prior transfusion associated graft versus host disease No other medical condition that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 weeks since prior immunotherapy or interferon alfa and recovered No prior autologous or allogeneic progenitor cell transplant Chemotherapy: See Disease Characteristics At least 3 weeks since prior chemotherapy and recovered Endocrine therapy: Not specified Radiotherapy: At least 3 weeks since prior radiotherapy and recovered Surgery: Not specified

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 49 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00005092
• Other Study ID Numbers: DM98-283; P30CA016672 ( U.S. NIH Grant/Contract ); MDA-DM-98283 ( Other Identifier: UT MD Anderson Cancer Center ); NCI-G00-1742; CDR0000067734 ( Registry Identifier: NCI PDQ )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: M.D. Anderson Cancer Center
• Study Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)

Investigators

• Study Chair: James Gajewski, MD; M.D. Anderson Cancer Center

• PRS Account: M.D. Anderson Cancer Center
• Verification Date: October 2018